Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (,19 keV/mm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual c-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ,1.48 in the SOBP and ,1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Drug Polymer Thermodynamic Phase Diagrams in the Selection of Optimal API-Polymer Compositions for Amorphous Solid Dispersions

Purpose The aim of this work was to examine, for amorphous solid dispersions, how the thermal analysis method selected impacts on the construction of thermodynamic phase diagrams, and to assess the predictive value of such phase diagrams in the selection of optimal, physically stable API-polymer compositions. Methods Thermodynamic phase diagrams for two API/polymer systems (naproxen/HPMC AS LF and naproxen/Kollidon 17 PF) were constructed from data collected using two different thermal analysis methods. The “dynamic” method involved heating the physical mixture at a rate of 1 &[deg]C/minute. In the "static" approach, samples were held at a temperature above the polymer Tg for prolonged periods, prior to scanning at 10 &[deg]C/minute. Subsequent to construction of phase diagrams, solid dispersions consisting of API-polymer compositions representative of different zones in the phase diagrams were spray dried and characterised using DSC, pXRD, TGA, FTIR, DVS and SEM. The stability of these systems was investigated under the following conditions: 25 &[deg]C, desiccated; 25 &[deg]C, 60 % RH; 40 &[deg]C, desiccated; 40 &[deg]C, 60 % RH. Results Endset depression occurred with increasing polymer volume fraction (Figure 1a). In conjunction with this data, Flory-Huggins and Gordon-Taylor theory were applied to construct thermodynamic phase diagrams (Figure 1b). The Flory-Huggins interaction parameter (&[chi]) for naproxen and HPMC AS LF was + 0.80 and + 0.72, for the dynamic and static methods respectively. For naproxen and Kollidon 17 PF, the dynamic data resulted in an interaction parameter of - 1.1 and the isothermal data produced a value of - 2.2. For both systems, the API appeared to be less soluble in the polymer when the dynamic approach was used. Stability studies of spray dried solid dispersions could be used as a means of validating the thermodynamic phase diagrams. Conclusion The thermal analysis method used to collate data has a deterministic effect on the phase diagram produced. This effect should be considered when constructing thermodynamic phase diagrams, as they can be a useful tool in predicting the stability of amorphous solid dispersions.

Unloading or not unloading? Sheep welfare implication of rest stop at control post after a 29h transport

In Europe, maximum journey time for transported sheep is set at 29. h (EC Regulation 1/2005), after which animals must be unloaded, fed and watered in control posts stopping for 24. h, as all other species, before continuing their journey. The industry considers these resting times too general, not taking into account the peculiar differences between species or age classes. Also, loading and unloading have been reported to be detrimental for the animals. Therefore, the industry pushes to reduce the times at control post and avoid unloading the animals from the truck. Since there is little information concerning the effect of resting in a stationary truck after long journeys, the present study aims to evaluate the effect of an 8. h rest stop on the truck for transported ewes compared to being unloaded for resting in a control post for the same amount of time, considering physiological and behavioural measures. Two groups of ewes were transported for 29. h, after which one was unloaded and housed in a pen (P) at the control post while the other was left inside the truck (T). After 8. h stop, a further 6. h travel was headed to the farm of origin. A third group (C) stayed at the farm as control. During the stop, standing, resting, moving and eating behaviour of all groups was recorded. Blood parameters, salivary and faecal cortisol were assessed at different stages. The behaviour of P animals during the resting period was more similar to C than to T ones, where feeding and lying behaviours were restricted by the limited space allowance on the truck. After returning to the farm of origin, both T and P animals showed different parameters' levels as compared to C. P ewes showed a mean loss weight of 2. kg not recorded in group T and showed higher signs of muscular damage compared to C group. It was concluded that, with so short resting times as 8. h, there is no clear advantages in terms of animal welfare for avoiding the unloading and loading of the animals in the control post after long journeys.

Service composition for biomedical applications

A exigente inovação na área das aplicações biomédicas tem guiado a evolução das tecnologias de informação nas últimas décadas. Os desafios associados a uma gestão, integração, análise e interpretação eficientes dos dados provenientes das mais modernas tecnologias de hardware e software requerem um esforço concertado. Desde hardware para sequenciação de genes a registos electrónicos de paciente, passando por pesquisa de fármacos, a possibilidade de explorar com precisão os dados destes ambientes é vital para a compreensão da saúde humana. Esta tese engloba a discussão e o desenvolvimento de melhores estratégias informáticas para ultrapassar estes desafios, principalmente no contexto da composição de serviços, incluindo técnicas flexíveis de integração de dados, como warehousing ou federação, e técnicas avançadas de interoperabilidade, como serviços web ou LinkedData. A composição de serviços é apresentada como um ideal genérico, direcionado para a integração de dados e para a interoperabilidade de software. Relativamente a esta última, esta investigação debruçou-se sobre o campo da farmacovigilância, no contexto do projeto Europeu EU-ADR. As contribuições para este projeto, um novo standard de interoperabilidade e um motor de execução de workflows, sustentam a sucesso da EU-ADR Web Platform, uma plataforma para realizar estudos avançados de farmacovigilância. No contexto do projeto Europeu GEN2PHEN, esta investigação visou ultrapassar os desafios associados à integração de dados distribuídos e heterogéneos no campo do varíoma humano. Foi criada uma nova solução, WAVe - Web Analyses of the Variome, que fornece uma coleção rica de dados de variação genética através de uma interface Web inovadora e de uma API avançada. O desenvolvimento destas estratégias evidenciou duas oportunidades claras na área de software biomédico: melhorar o processo de implementação de software através do recurso a técnicas de desenvolvimento rápidas e aperfeiçoar a qualidade e disponibilidade dos dados através da adopção do paradigma de web semântica. A plataforma COEUS atravessa as fronteiras de integração e interoperabilidade, fornecendo metodologias para a aquisição e tradução flexíveis de dados, bem como uma camada de serviços interoperáveis para explorar semanticamente os dados agregados. Combinando as técnicas de desenvolvimento rápidas com a riqueza da perspectiva "Semantic Web in a box", a plataforma COEUS é uma aproximação pioneira, permitindo o desenvolvimento da próxima geração de aplicações biomédicas.

Análise da resistência à fadiga de tubos de aço API 5CT N80 Tipo Q soldados via processo de indução magnética de alta frequência (HFIW)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

GuideMe: service for consulting, publication and recommendation of touristic locations

Trabalho de Projeto realizado para obtenção do grau de Mestre em Engenharia Informática e de Computadores

Desenvolvimento de uma aplicação móvel para apoio a pessoas com perturbações psicóticas

A presente dissertação tem como objectivo descrever o trabalho desenvolvido sobre o projecto iCOPE, uma plataforma dedicada ao auxilio do processo psicoterapêutico para pessoas com perturbações psicóticas. A sua concepção e motivada pela necessidade de fornecer um meio psicoterapêutico com base na portabilidade dos dispositivos móveis. O desenvolvimento foi conseguido através de uma colaboração multidisciplinar, orientada por especialistas de terapia ocupacional, e pela engenharia de software. O iCOPE é um sistema centralizado, no qual o progresso de um paciente é registado e monitorizado através de outra aplicação, por um terapeuta designado. Esta filosofia levou à criação de uma API baseada em REST, capaz de comunicar com uma base de dados. A construção da API concretizou-se com recurso a linguagem PHP, aliada a micro-framework Slim. O objectivo desta API passa não só pela necessidade de fornecer um sistema acessível, mas também com a ambição de conceber uma plataforma com um potencial escalável e expansível, para o caso de ser necessário implementar novas funcionalidades futuras (future-proof). O autor desta dissertação foi responsável pelo levantamento de requisitos, o desenvolvimento da aplicação móvel, o desenvolvimento colaborativo do modelo de dados e base de dados e da interface da API de comunicação. No fim do desenvolvimento foi feita uma apreciação funcional pelos utilizadores alvo, que realizaram uma avaliação sobre a utilização e integração da aplicação no seu tratamento. Face aos resultados obtidos foram tiradas conclusões sobre o futuro desenvolvimento da aplicação e que outros aspectos poderiam ser integrados para efectivamente chegar a mais pacientes.

Avaliação dos mecanismos de concorrência na API do Java 8

As plataformas com múltiplos núcleos tornaram a programação paralela/concorrente num tópico de interesse geral. Diversos modelos de programação têm vindo a ser propostos, facilitando aos programadores a identificação de regiões de código potencialmente paralelizáveis, deixando ao sistema operativo a tarefa de as escalonar dinamicamente em tempo de execução, explorando o maior grau possível de paralelismo. O Java não foge a esta tendência, disponibilizando ao programador um número crescente de bibliotecas de mecanismos de sincronização e paralelização de código. Neste contexto, esta tese apresenta e discute um conjunto de resultados obtidos através de testes intensivos à eficiência de algoritmos de ordenação implementados com recurso aos mecanismos de concorrência da API do Java 8 (Threads, Threadpools, ExecutorService, CountdownLach, ExecutorCompletionService e ForkJoinPools) em sistemas com um número de núcleos variável. Para cada um dos mecanismos, são apresentadas conclusões sobre o seu funcionamento e discutidos os cenários em que o seu uso pode ser rentabilizado de modo a serem obtidos melhores tempos de execução.

Noise traders, rational traders, and the rest: A new approach to efficient financial markets

A PhD Dissertation, presented as part of the requirements for the Degree of Doctor of Philosophy from the NOVA - School of Business and Economics

REST Regulates Oncogenic Properties of Glioblastoma Stem Cells.

Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor repressor element 1 silencing transcription factor (REST), suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM. STEM CELLS 2012;30:405-414.

The role of skeletal muscle PLIN proteins at rest and following lipolytic stimulation

This thesis investigated the subcellular location of skeletal muscle PLIN proteins (PLIN2, PLIN3, and PLIN5) as well as protein interactions with ATGL and HSL at rest and following lipolytic stimulation. In addition, the serine phosphorylation state of PLIN2, PLIN3, and PLIN5 was determined at rest and following lipolytic stimulation. An isolated whole muscle technique was used to study the effects of contraction and epinephrine-induced lipolysis. This method allowed for the examination of the effects of contraction and epinephrine alone and in combination. Further, the soleus was chosen for investigating the role of PLIN proteins in skeletal muscle lipolysis due to its suitability for isolated incubation, and the fact that it is primarily oxidative in nature (~80% type I fibres). It has also been previously shown to have the greatest reliance on lipid metabolism and for this reason is ideal for investigating the role of PLIN proteins in lipolysis. Immunofluorescence microscopy revealed that skeletal muscle lipid droplets are partially co-localized to both PLIN2 and PLIN5 and that contraction does not affect the amount of colocalization, indicating that PLIN5 is not recruited to lipid droplets with contraction (PLIN2 ~65%; PLIN5 ~56%). Results from the immunoprecipitation studies revealed that with lipolysis in skeletal muscle the interaction between ATGL and CGI-58 is increased (study 2: 128% with contraction, p<0.05; study 3: 50% with contraction, 25% epinephrine, 80% contraction + epinephrine, p>0.05). Further PLIN2, PLIN3, and PLIN5 all interact with ATGL and HSL, while only PLIN3 and PLIN5 interact with CGI-58. Among these interactions, the association between PLIN2 and ATGL decreases with lipolytic stimulation (study 2: 21% with contraction, p<0.05). Finally our results demonstrate that PLIN3 and PLIN5 are serine phosphorylated at rest and that the level of phosphorylation remains unchanged in the face of either contractile or adrenergic stimulation. In summary, the regulation of skeletal muscle lipolysis is a complex process involving multiple proteins and enzymes. The skeletal muscle PLIN proteins likely play a role in skeletal muscle lipid droplet dynamics, and the data from this thesis indicate that these proteins may work together in regulating lipolysis by interaction with both ATGL and HSL.

Estudio de la susceptibilidad a la corrosión bajo esfuerzos de uniones en tuberías de acero API 5L, X70 obtenidas por soldadura SMAW y MMA.

Tesis (Maestría en Ciencias de la Ingeniería Mecánica con Especialidad en Materiales) UANL, 2013.

Rest-activity cycle disturbances in the acute phase of moderate to severe traumatic brain injury

Background. Sleep-wake disturbances are among the most persistent sequelae after traumatic brain injury (TBI) and probably arise during the hospital stay following TBI. These disturbances are characterized by difficulties sleeping at night and staying awake during the day. Objective. The aim of the present study was to document rest-activity cycle consolidation in acute moderate/severe TBI using actigraphy and to assess its association with injury severity and outcome. Methods. In all, 16 hospitalized patients (27.1 ± 11.3 years) with moderate/severe TBI wore actigraphs for 10 days, starting in the intensive care unit (ICU) when continuous sedation was discontinued and patients had reached medical stability. Activity counts were summed for daytime (7:00-21:59 hours) and nighttime periods (22:00-6:59 hours). The ratio of daytime period activity to total 24-hour activity was used to quantify rest-activity cycle consolidation. An analysis of variance was carried out to characterize the evolution of the daytime activity ratio over the recording period. Results. Rest-activity cycle was consolidated only 46.6% of all days; however, a significant linear trend of improvement was observed over time. Greater TBI severity and longer ICU and hospital lengths of stay were associated with poorer rest-activity cycle consolidation and evolution. Patients with more rapid return to consolidated rest-activity cycle were more likely to have cleared posttraumatic amnesia and have lower disability at hospital discharge. Conclusions. Patients with acute moderate/ severe TBI had an altered rest-activity cycle, probably reflecting severe fragmentation of sleep and wake episodes, which globally improved over time. A faster return to rest-activity cycle consolidation may predict enhanced brain recovery.