The synthesis of new 6-hydrazinopurines as potential anticancer agents

[Excerpt] Purines, such as adenine, are one of the most important naturally occurring nitrogen heterocycles and they are frequently used as bioactive agents.[1,2] The increasing number of synthetic purines reveals the great potential of these compounds as enzyme inhibitors. Protein Kinases have an important regulatory role in cell proliferation, differentiation and signalling processes. Abnormal signal transduction is responsible for devastating diseases such as cancer. All of the protein kinases identified have in common the cofactor ATP indicating that the adenine nucleus is a very important scaffold for discovery of new anti-cancer agents.[3,4] Previous work identified a modest anticancer activity in a family of 6-arylaminopurines. In the view of these results, it seemed reasonable to assume that some interesting anticancer agents might result by replacement of the phenyl group by a secondary amino group linked to the N-6 atom of the adenine moiety. (...)

Volumetric alterations in the nucleus accumbens and caudate nucleus in bulimia nervosa: a structural magnetic resonance imaging study

Bulimia nervosa (BN) is an eating disorder characterized by recurrent episodes of binge eating and inappropriate compensatory behaviors (such as purging, fasting, or excessive exercise) to prevent weight gain. BN has been associated with deficits in inhibitory control processes. The basal ganglia specifically, the nucleus accumbens (NAc) and the caudate nucleus (CN) are part of the frontostriatal circuits involved in inhibitory control. The main goal of this study was to investigate the presence of morphological alterations in the NAc and the CN in a sample of patients diagnosed with BN.

Galanin-mediated behavioural hyperalgesia from the dorsomedial nucleus of the hypothalamus involves two independent descending pronociceptive pathways

Activation of the dorsomedial nucleus of the hypothalamus (DMH) by galanin (GAL) induces behavioural hyperalgesia. Since DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt), a pronociceptive region projecting to the spinal dorsal horn (SDH) and/or the serotoninergic raphe-spinal pathway acting on the spinal 5-HT3 receptor (5HT3R) could relay descending nociceptive facilitation induced by GAL in the DMH. Heat-evoked paw-withdrawal latency (PWL) and activity of SDH neurones were assessed in monoarthritic (ARTH) and control (SHAM) animals after pharmacological manipulations of the DMH, DRt and spinal cord. The results showed that GAL in the DMH and glutamate in the DRt lead to behavioural hyperalgesia in both SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of pain behaviour induced by GAL in the DMH was reversed by lidocaine in the DRt and by ondansetron, a 5HT3R antagonist, in the spinal cord. However, the hyperalgesia induced by glutamate in the DRt was not blocked by spinal ondansetron. In addition, in ARTH but not SHAM animals PWL was increased after lidocaine in the DRt and ondansetron in the spinal cord. Our data demonstrate that GAL in the DMH activates two independent descending facilitatory pathways: (i) one relays in the DRt and (ii) the other one involves 5-HT neurones acting on spinal 5HT3Rs. In experimental ARTH, the tonic pain-facilitatory action is increased in both of these descending pathways.

Study of the retinoic acid regulated genes in the rodent hypothalamus controlling growth and appetite and the potential for the epigenetic control

Dissertação de mestrado em Bioquímica (área de especialização em Biomedicina)

Experimental procedures for the identification of material properties of intervertebal disc - a contribution for the development of biomimetic substitutes for the nucleus pulposus

Tese de Doutoramento em Engenharia Mecânica.

Generic system for human-computer gesture interaction: applications on sign language recognition and robotic soccer refereeing

Hand gestures are a powerful way for human communication, with lots of potential applications in the area of human computer interaction. Vision-based hand gesture recognition techniques have many proven advantages compared with traditional devices, giving users a simpler and more natural way to communicate with electronic devices. This work proposes a generic system architecture based in computer vision and machine learning, able to be used with any interface for human-computer interaction. The proposed solution is mainly composed of three modules: a pre-processing and hand segmentation module, a static gesture interface module and a dynamic gesture interface module. The experiments showed that the core of visionbased interaction systems could be the same for all applications and thus facilitate the implementation. For hand posture recognition, a SVM (Support Vector Machine) model was trained and used, able to achieve a final accuracy of 99.4%. For dynamic gestures, an HMM (Hidden Markov Model) model was trained for each gesture that the system could recognize with a final average accuracy of 93.7%. The proposed solution as the advantage of being generic enough with the trained models able to work in real-time, allowing its application in a wide range of human-machine applications. To validate the proposed framework two applications were implemented. The first one is a real-time system able to interpret the Portuguese Sign Language. The second one is an online system able to help a robotic soccer game referee judge a game in real time.

Generic system for human-computer gesture interaction

Hand gestures are a powerful way for human communication, with lots of potential applications in the area of human computer interaction. Vision-based hand gesture recognition techniques have many proven advantages compared with traditional devices, giving users a simpler and more natural way to communicate with electronic devices. This work proposes a generic system architecture based in computer vision and machine learning, able to be used with any interface for humancomputer interaction. The proposed solution is mainly composed of three modules: a pre-processing and hand segmentation module, a static gesture interface module and a dynamic gesture interface module. The experiments showed that the core of vision-based interaction systems can be the same for all applications and thus facilitate the implementation. In order to test the proposed solutions, three prototypes were implemented. For hand posture recognition, a SVM model was trained and used, able to achieve a final accuracy of 99.4%. For dynamic gestures, an HMM model was trained for each gesture that the system could recognize with a final average accuracy of 93.7%. The proposed solution as the advantage of being generic enough with the trained models able to work in real-time, allowing its application in a wide range of human-machine applications.

The synthesis of novel 5-aminoimidazoles derivatives with anticancer activity

[Excerpt] The imidazole nucleus is present in a significant number of biomolecules and the inclusion of this moiety in organic scaffolds is considered an important synthetic strategy in drug discovery.[1] 5-Aminoimidazoles are interesting building blocks in medicinal chemistry since they are key components in many bioactive molecules and their derivatives showed a wide pharmacological potential as anticancer drugs.[1] The hydrazones constitute an important class of biological active drug molecules due to their wide range of pharmacological properties that include antitumoral activities.[2] Amidrazone derivatives could be considered very promising in the perspective of new drug discovery, because they are very effective as building blocks to obtain various heterocycles.[2,3] The α-hydrazononitriles are a special case of compounds belonging to the family of hydrazones that is less common in the literature, but has a great interest due to their pharmacological applications.[4] (...)

Estudo de validação do Partner Interaction Questionnaire para fumantes e ex-fumantes

O presente artigo tem por objetivo validar uma versão adaptada do Partner Interaction Questionnaire (PIQ), instrumento que avalia o suporte para deixar de fumar dado pelo parceiro. É apresentada uma versão adaptada do PIQ para fumantes e abstinentes. Participaram no estudo 224 fumantes (52.7% do sexo feminino e 47.3% do sexo masculino; média de idades=28.6 anos; DP=8.69) e 169 ex-fumantes (68.6% do sexo masculino e 31.4% do sexo feminino; média de idades= 43.1 anos; DP=13.02). O instrumento apresentou boa fidelidade (alfa de Cronbach: 0.73) para a subescala positiva e para a subescala negativa (alfa de Cronbach: 0.77). O estudo de validade revelou a presença de dois fatores que explicam 43.36% da variância. O instrumento apresenta boa validade de construto, correlacionando-se positivamente com o ajustamento de casais e a qualidade de vida mental, e negativamente com a depressão. Esta versão adaptada do PIQ reuniu as condições necessárias para a sua aplicação em fumantes e ex-fumantes, podendo ser uma escala útil em programas de intervenção de cessação tabágica e de manutenção da abstinência.

Analysis of physicochemical interaction between the components of asphalt mixtures with rubber

Tese de Doutoramento em Engenharia Civil

Careers, identities and professionalization. A study on doctors about their social representations related to the labor market today and its foreseeable future

This study is in line with the analyses of university and working career in their interaction in relation with conditioning factors. It comprises two central issues: the issue of identity bound to the issue of professionalization within the domain of training and employment. Nowadays, professionalization of the individuals, inside a troubled occupational world, demands the implementation of mechanisms favoring the development of both the individuals and the institution in which they work. All this has an impact at the local, regional and even national levels. Three levels of analysis interplay from a sui generis perspective: macro-meso-micro-macro (Aparicio, 2005; 2007a; 2007b, 2013a, 2014, 2015 b, d – See the Three- Dimensional Spiral of Sense Theory). The aim was to be aware of the doctors’ representations regarding the value of such degree under the present “degree devaluation”, and its impact on the professional future as well as on the core issues of the labor market which need urgent measures with a view to a belter interaction between the two systems. The methodology used was quanti-qualitative (semi-structured questionnaires, interviews, and hierarchical evocations). The population consisted of doctors (2005-2012) from the National University of Cuyo, in Argentina. The results helped us understand the nucleus of such representations and the peripheral aspects by career and institution, thus revealing professional and disciplinary identities. The professional identities show the situated needs in terms of professionalization within the different contexts and, particularly, within the labor market.