A simple closed-loop membrane process for the purification of active pharmaceutical ingredients

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Leveraging facebook’s open graph to develop an environmental persuasive application

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Coherent structures in open channel flows with bed load transport over an hydraulically rough bed

Dissertação para obtenção do Grau de Mestre em Engenharia Civil – Perfil de Estruturas

Implementação de uma solução open source de Business Intelligence com metodologia Ágil

A importância dos sistemas de data warehousing e business intelligence é cada vez mais pronunciada, no sentido de dotar as organizações com a capacidade de guardar, explorar e produzir informação de valor acrescido para os seus processos de tomada de decisão. Esta realidade é claramente aplicável aos sectores da administração pública portuguesa e, muito em particular, aos organismos com responsabilidades centrais no Ministério da Saúde. No caso dos Serviços Partilhados do Ministério da Saúde (SPMS), que tem como missão prover o SNS de sistemas centrais de business intelligence, o apelo dos seus clientes, para que possam contar com capacidades analíticas nos seus sistemas centrais, tem sido sentido de forma muito acentuada. Todavia, é notório que, tanto os custos, como a complexidade, de grande parte destes projetos têm representado uma séria ameaça à sua adoção e sucesso. Por um lado, a administração pública tem recebido um forte encorajamento para integrar e adotar soluções de natureza open source (modelo de licenciamento gratuito), para os seus projetos de sistemas de informação. Por outro lado, temos vindo a assistir a uma vaga de aceitação generalizada de novas metodologias de desenvolvimento de projetos informáticos, nomeadamente no que diz respeito às metodologias Agéis, que se assumem como mais flexíveis, menos formais e com maior grau de sucesso. No sentido de averiguar da aplicabilidade do open source e das metodologias Ágeis aos sistemas de business intelligence, este trabalho documenta a implementação de um projeto organizacional para a SPMS, com recurso a ferramentas open source de licenciamento gratuito e através de uma metodologia de desenvolvimento de natureza Ágil.

Strengthening to seismic action of reinforced columns with rectangular cross-section

The first part of this research work regards the assessment of the mathematical modelling of reinforced concrete columns confined with carbon fibre (CFRP) sheets under axial loading. The purpose was to evaluate existing analytical models, contribute to possible improvements and choose the best model(s) to be part of a new model for the prediction of the behaviour of confined columns under bending and compression. For circular columns, a wide group of authors have proposed several models specific for FRP-confined concrete. The analysis of some of the existing models was carried out by comparing these with several tested columns. Although several models predict fairly the peak load only few can properly estimate the load-strain and dilation behaviour of the columns. Square columns confined with CFRP show a more complex interpretation of their behaviour. Accordingly, the analysis of two experimental programs was carried out to propose new modelling equations for the whole behaviour of columns. The modelling results show that the analytical curves are in general agreement with the presented experimental curves for a wide range of dimensions. An analysis similar to the one done for circular columns was this turn carried out for square columns. Few models can fairly estimate the whole behaviour of the columns and with less accuracy at all levels when compared with circular columns. The second part of this study includes seven experimental tests carried out on reinforced concrete rectangular columns with rounded corners, different damage condition and with confinement and longitudinal strengthening systems. It was concluded that the use of CFRP confinement is viable and of effective performance enhancement alone and combined with other techniques, maintaining a good ductile behaviour for established threshold displacements. As regards the use of external longitudinal strengthening combined with CFRP confinement, this system is effective for the performance enhancement and viable in terms of execution. The load capacity was increased significantly, preserving also in this case a good ductile behaviour for threshold displacements. As to the numerical nonlinear modelling of the tested columns, the results show a variation of the peak load of 1% to 10% compared with tests results. The good results are partly due to the inclusion of the concrete constitutive model by Mander et al. modified by Faustino, Chastre & Paula taking into account the confinement effect. Despite the reasonable approximation to tests results, the modelling results showed higher unloading, which leads to an overestimate dissipated energy and residualdisplacement.

Primary cilia and the regulation of hedgehog signaling: link to cardiac development

RESUMO: As células eucarióticas evoluíram um sistema de sinalização complexo que lhes permite responder aos sinais extracelulares e intracelulares. Desta forma, as vias de sinalização são essenciais para a sobrevivência da célula e do organismo, uma vez que regulam processos fundamentais, tais como o desenvolvimento, o crescimento, a imunidade, e a homeostase dos tecidos. A via de transdução de sinal Hedgehog (Hh) envolve o receptor Patched1 (Ptch1), que tem um efeito inibidor sobre a proteína Smoothened (Smo) na ausência dos seus ligandos, as proteínas Sonic hedgehog (Shh). Estas proteínas são reguladores fundamentais do desenvolvimento embrionário, como ilustrado pelas malformações drásticas observadas em embriões humanos e de murganho com perturbações da transdução de sinal da via Hh e que incluem polidactilia, defeitos craniofaciais e malformações ósseas. Igualmente importantes são as consequências da ativação inapropriada da via de sinalização Hh na formação de tumores. Curiosamente, os componentes desta via localizam-se nos cílios primários. Além disso, demonstrou-se que esta localização é crucial para a sinalização através da via Hh. Na presença dos ligandos, Ptch1 é internalizado e destinado a degradação ou sequestrado num compartimento da célula de onde não pode desempenhar o seu papel inibitório. A proteína Arl13b é uma pequena GTPase pertencente à família Arf/Arl da superfamília Ras de pequenas GTPases e foi implicada no síndrome de Joubert, uma ciliopatia caracterizada por ataxia congénita cerebelar, hipotonia, atrso mental e cardiopatia congénita. Murganhos deficientes para Arl13b, chamado hennin (hnn) morrem morrem prematuramente ao dia 13,5 de gestação (E13,5) e exibem anomalias morfológicas nos cílios que levam à interrupção da sinalização Hh. Além disso, a Arl13b está diretamente envolvida na regulação da via Hh, controlando a localização de vários componentes desta via nos cílios primários. Neste trabalho, mostramos que a Arl13b se localiza em circular dorsal ruffles (CDRs), que são estruturas de actina envolvidas em macropinocitose e internalização de recetores, e que regula a sua formação. Além disso, aprofundámos o conhecimento do processo de ativação da via de sinalização Hh, mostrando que as CDRs sequestram seletivamente e internalizam o recetor Ptch1. As CDRs formam-se minutos após ativação da via por ligandos Shh ou pelo agonista de Smo SAG e continuam a ser formadas a partir daí, sugerindo uma indução contínua da reorganização do citoesqueleto de actina quando a via está ativada. Observámos ainda que a inibição da formação de CDRs através do silenciamento de WAVE1, uma proteína necessária para a formação destas estruturas, resulta na diminuição da ativação da via de sinalização Hh. Além disso, o bloqueio da macropinocitose, que se segue ao fecho das CDRs, através do silenciamento de uma proteína necessária para a cisão de macropinossomas, nomeadamente a proteína BARS, tem um efeito semelhante. Estes resultados sugerem que as CDRs e a macropinocitose são necessárias para a ativação da via de sinalização Hh e indicam que esta via de internalização controla os níveis de sinal Hh. Durante o desenvolvimento, as células proliferativas dependem do cílio primário para a transdução de várias vias de sinalização. A via Hh induz a diferenciação do músculo cardíaco. Por conseguinte, os murganhos deficientes na via de sinalização Hh exibem uma variedade de defeitos de lateralidade, incluindo alteração do looping do coração, como pode ser visto em murganhos deficientes para Arl13b. Por conseguinte, investigámos o papel da Arl13b no desenvolvimento do coração. Mostramos que a Arl13b é altamente expressa no coração de embriões de murganho e de murganhos adultos ao nível do mRNA e da proteína. Além disso, o perfil de distribuição da Arl13b no coração segue o dos cílios primários, que são essenciais para o desenvolvimento cardíaco. Corações de murganhos hnn no estadio E12,5 mostram um canal átrio-ventricular aberto, espessamento da camada compacta ventricular e aumento do índice mitótico no ventrículo esquerdo. Além disso, um atraso de 1 a 2 dias no desenvolvimento é observado em corações de murganhos hnn, quando comparados com controlos selvagens no estadio E13,5. Assim, estes resultados sugerem que a Arl13b é necessária para o desenvolvimento embrionário do coração e que defeitos cardíacos podem contribuir para a letalidade embrionária de murganhos hnn. Em suma, foi estabelecido um novo mecanismo para a regulação dos níveis de superfície do recetor Ptch1, que envolve a remodelação do citoesqueleto de actina e a formação de CDRs após a ativação da via de sinalização Hh. Este mecanismo permite um feedback negativo que evita a repressão excessiva da via através da remoção de Ptch1 da superfície da célula. Além disso, determinou-se que uma mutação de perda de função na Arl13b causa defeitos cardíacos durante o desenvolvimento, possivelmente relacionados com a associação dos defeitos em cílios primários e na sinalização Hh, existentes em murganhos deficientes para Arl13b. A via de sinalização Hh tem tido um papel central entre as vias de sinalização, uma vez que a sua regulação é crucial para o funcionamento apropriada da célula. Assim, a descoberta de um novo mecanismo de tráfego através de macropinocitose e CDRs que controla a ativação e repressão da via de sinalização Hh traz novas perspetivas de como esta via pode ser regulada e pode ainda conduzir à identificação de novos alvos e estratégias terapêuticas. --------------------ABSTRACT: Eukaryotic cells have evolved a complex signaling system that allows them to respond to extracellular and intracellular cues. Signaling pathways are essential for cell and organism survival, since they regulate fundamental processes such as development, growth, immunity, and tissue homeostasis. The Hedgehog (Hh) pathway of signal transduction involves the receptor Patched1 (Ptch1), which has an inhibitory effect on Smoothened (Smo) in the absence of its ligands, the Sonic hedgehog (Shh) proteins. These proteins are fundamental regulators of embryonic development, as illustrated by the dramatic malformations seen in human and mouse embryos with perturbed Hh signal transduction that include polydactyly, craniofacial defects and skeletal malformations. Equally important are the consequences of inappropriate activation of the Hh signaling response in tumor formation. Interestingly, the components of this pathway localize to primary cilia. Moreover, it has been shown that this localization is crucial for Hh signaling. However, in the presence of the ligands, Ptch1 is internalized and destined for degradation or sequestered in a cell compartment where it no longer can play its inhibitory role. ADP-ribosylation factor-like (Arl) 13b, a small GTPase belonging to Arf/Arl family of the Ras superfamily of small GTPases has been implicated in Joubert syndrome, a ciliopathy characterized by congenital cerebellar ataxia, hypotonia, intellectual disability and congenital heart disease. Arl13b-deficient mice, called hennin (hnn) die at embryonic day 13.5 (E13.5) and display morphological abnormalities in primary cilia that lead to the disruption of Hh signaling. Furthermore, Arl13b is directly involved in the regulation of Hh signaling by controlling the localization of several components of this pathway to primary cilia. Here, we show that Arl13b localizes to and regulates the formation of circular dorsal rufles (CDRs), which are actin-basedstructures known to be involved in macropinocytosis and receptor internalization. Additionally, we extended the knowledge of the Hh signaling activation process by showing that CDRs selectively sequester and internalize Ptch1 receptors. CDRs are formed minutes after Hh activation by Shh ligands or the Smo agonist SAG and keep being formed thereafter, suggesting a continuous induction of actin reorganization when the pathway is switched on. Importantly, we observed that disruption of CDRs by silencing WAVE1, a protein required for CDR formation, results in down-regulation of Hh signaling activation. Moreover, the blockade of macropinocytosis, which follows CDR closure, through silencing of a protein necessary for the fission of macropinosomes, namely BARS has a similar effect. These results suggest that CDRs and macropinocytosis are necessary for activation of Hh signaling and indicate that this pathway of internalization controls Hh signal levels. During development, proliferating cells rely on the primary cilium for the transduction of several signaling pathways. Hh induces the differentiation of cardiac muscle. Accordingly, Hh-deficient mice display a variety of laterality defects, including alteration of heart looping, as seen in Arl13b-deficient mice. Therefore, we investigated the role of Arl13b in heart development. We show that Arl13b is highly expressed in the heart of both embryonic and adult mice at mRNA and protein levels. Also, Arl13b localization profile mimics that of primary cilia, which have been shown to be essential to early heart development. E12.5 hnn hearts show an open atrioventricular channel, increased thickening of the ventricular compact layer and increased mitotic index in the left ventricle. Moreover, a delay of 1 to 2 days in development is observed in hnn hearts, when compared to wild-type controls at E13.5. Hence, these results suggest that Arl13b is necessary for embryonic heart development and that cardiac defects might contribute to the embryonic lethality of hnn mice. Altogether, we established a novel mechanism for the regulation of Ptch1 surface levels, involving cytoskeleton remodeling and CDR formation upon Hh signaling activation. This mechanism allows a negative feedback loop that prevents excessive repression of the pathway by removing Ptch1 from the cell surface. Additionally, we determined that the Arl13b loss-offunction mutation causes cardiac defects during development, possibly related to the associated ciliary and Hh signaling defects found in Arl13b-deficient mice. Hh signaling has taken a center stage among the signaling pathways since its regulation is crucial for the appropriate output and function of the cell. Hence, the finding of a novel trafficking mechanism through CDRs and macropinocytosis that controls Hh signaling activation and repression brings new insights to how this pathway can be regulated and can lead to the discovery of novel therapeutic targets and strategies.

Rectangular flaps technique for treatment of congenital hand syndactyly

The authors analysed a series of 22 patients undergoing surgical correction of congenital hand syndactyly by the rectangular flap technique. Using our evaluation method, we found that good functional and aesthetic results were obtained in 77.3% of the patients, with a complication rate of 13.6%. We concluded that the rectangular flap technique has a simple design, is easily reproducible by in-training staff, has good results, and can be applied on the majority of the syndactyly cases.

Comuns: An Open-Data Provider, Explorer and Analytic Toolbox Based on FOSS

Contém resumo

Laparoscopic versus open splenectomy in the management of hematologic diseases

Splenectomy is the best available treatment for severe forms of hereditary spherocytosis, idiopathic thrombocytopenic purpura, and other hematologic conditions when these prove refractory to conservative management. It has been employed for many decades with low mortality and favorable remission rates. The use of laparoscopic splenectomy in recent years has been rapidly and even enthusiastically adopted in this field. However, the exact role of laparoscopic versus open surgery for hematologic diseases is still debated. In this study of 58 adult patients, laparoscopic procedures were compared with conventional splenectomies for similar indications. METHODS: All patients were operated on within an 8-year period. Subjects underwent similar procedures under the supervision of the same surgical school and were compared regarding age, gender, body mass index, and diagnosis. Laparoscopically managed cases (Group I, n = 30) were prospectively followed according to a written protocol, whereas the same investigation was retrospectively done with regard to traditional laparotomy (Group II, n = 28). Methods included general and demographic findings, duration and technical steps of operation, blood loss, weight of spleen, need for conversion (in minimally invasive subjects), intraoperative and postoperative complications, time until realimentation, postoperative hospitalization, mortality, and late follow-up including recurrence rate. RESULTS: Idiopathic thrombocytopenic purpura was the surgical indication in over 50% of the patients in both groups, but familial spherocytosis, thalassemia, myelodysplasia, and lymphomas were also represented in this series. Laparoscopic procedures took more time to perform (P = 0.004), and postoperative hospitalization was 2 days shorter, but this difference was not statistically significant. Postoperative hematocrit and volume of blood transfusions was equivalent, although the laparoscopic cases had a somewhat lower preoperative hematocrit (NS) and displayed better recovery for this measurement (P = 0.03). More patients in Group I were able to accept oral food on the first day than subjects undergoing conventional operations (P < 0.05). Relatively few conversions were necessary during the minimally invasive surgeries (13.3%), and postoperative early and late complications as well as recurrences occurred in similar proportions. Also, the mean weight of the spleen was not statistically different between the groups, although there was a marked numerical tendency toward larger masses in conventional procedures. No spleen in Group I exceeded 2.0 kg, whereas in Group II values up to 4.0 kg occurred, and the mean weight was 50% higher in the latter group. CONCLUSIONS: 1) Minimally invasive splenectomy was essentially comparable to open surgery with regard to safety, efficacy, and late results; 2) Advantages concerning shorter postoperative hospitalization could not be shown, despite earlier food intake and a non-significant tendency toward earlier discharge; 3) This new modality should be considered an option in cases of hematologic conditions whenever the spleen is not hugely enlarged.

Plastic waste use as aggregate and binder modifier in open-graded asphalts

Road pavements are very important infrastructures for the Society, but they can cause serious environmental impacts during construction, operation and rehabilitation phases. Thus, it is essential to develop surface paving solutions that promote not only the durability but also a comfortable and safe use. In fact, this work aims to study the properties of new opengraded mixtures for surface layers produced with plastic wastes. First, HDPE and EVA wastes were used as bitumen modifiers, and then another plastic waste (PEX) replaced part of the aggregates. After studying the modified binders, the open-graded mixtures were designed, and then they were tested concerning their particle loss, rutting resistance, surface texture and damping effect. It was concluded that both ways of using the plastic wastes can improve the mechanical and functional properties of the open-graded mixtures related to the pavement performance.

State of the art and open questions on cathode preparation based on carbon coated lithium iron phosphate

One important component with particular relevance in battery performance is the cathode, being one of the main responsible elements for cell capacity and cycle life. Carbon coated lithium iron phosphate, C-LiFePO4, active material is one of the most promising cathode materials for the next generation of large scale lithium ion battery applications and strong research efforts are being devoted to it, due to its excellent characteristics, including high capacity, ~170 mAh/g, and safety. This review summarizes the main developments on C-LiFePO4 based cathode film preparation and performance. The effect of the binder, conductive additive, relationship between active material-binder-conductive additive and drying step, in the electrode film fabrication and performance is presented and discussed. Finally, after the presentation of the cell types fabricated with C-LiFePO4 active material and their performance, some conclusions and guidelines for further investigations are outlined.

User expectations for media sharing practices in open display networks

Open Display Networks have the potential to allow many content creators to publish their media to an open-ended set of screen displays. However, this raises the issue of how to match that content to the right displays. In this study, we aim to understand how the perceived utility of particular media sharing scenarios is affected by three independent variables, more specifically: (a) the locativeness of the content being shared; (b) how personal that content is and (c) the scope in which it is being shared. To assess these effects, we composed a set of 24 media sharing scenarios embedded with different treatments of our three independent variables. We then asked 100 participants to express their perception of the relevance of those scenarios. The results suggest a clear preference for scenarios where content is both local and directly related to the person that is publishing it. This is in stark contrast to the types of content that are commonly found in public displays, and confirms the opportunity that open displays networks may represent a new media for self-expression. This novel understanding may inform the design of new publication paradigms that will enable people to share media across the display networks.

Repository power: how repositories can support Open Access mandates

Many funding agencies have Open Access mandates in place, but how often are scientific publications as outputs linked to funding details? The benefits of linking funding information to publications as part of the deposit workflow can assist in adhering to Open Access mandates. This paper examines how OpenAIRE – Open Access Infrastructure for Research in Europe – can ease monitoring Open Access and reporting processes for funders, and presents some results and opportunities. It also outlines how it relies on cleaned and curated repository content, a vital cog in the ever turning wheel of the global scholarly landscape, and the benefits it brings.

FOSTER: facilitate open science training for european research

FOSTER aims to support different stakeholders, especially young researchers, in adopting open access in the context of the European Research Area (ERA) and in complying with the open access policies and rules of participation set out for Horizon 2020 (H2020). FOSTER establish a European-wide training programme on open access and open data, consolidating training activities at downstream level and reaching diverse disciplinary communities and countries in the ERA. The training programme includes different approaches and delivery options: elearning, blearning, self-learning, dissemination of training materials/contents, helpdesk, face-to-face training, especially training-the-trainers, summer schools, seminars, etc.