European Spallation Source (ESS), the next-generation neutron source facility, is expected to pro... more European Spallation Source (ESS), the next-generation neutron source facility, is expected to produce an immense amount of data. Various working groups mostly associated with the EU project BrightnESS aim at developing solutions for its data-intensive challenges. The real-time data management and aggregation is among the top priorities. The Apache KAFKA framework will be the base for ESS real-time distributed data streaming. One of the major challenges is the simulation of data streams from experimental data generation to data analysis and storage. This presentation outlines a simulation approach based on the DonkiOrchestra data acquisition and experiment control framework, re-purposed as a data streaming simulation system compatible with the ESS-KAFKA infrastructure.
RODRIGUES, A. M., F. I. PITACAS, C. M. G. REIS and M. BLASCO, 2016. Nutritional value of Opuntia ... more RODRIGUES, A. M., F. I. PITACAS, C. M. G. REIS and M. BLASCO, 2016. Nutritional value of Opuntia ficusindica cladodes from Portuguese ecotypes. Bulg. J. Agric. Sci., 22: 40–45 The use of Opuntia ficus-indica cladodes as a forage for ruminants has been very important in the semi-arid and arid regions of the world. O. ficus-indica cladodes can be fed to small ruminants especially in periods of the year when there is low quality and quantity of pasture. In Mediterranean regions like South of Portugal during the rainy season the availability of pasture is quantitatively and qualitatively satisfactory, but in critical times of the year the shortage and low nutritive value of forages causes decreased productivity in the ruminant’s production of milk and meat. The aim of this study was to evaluate the nutritional profile of the cladodes from five different Portuguese ecotypes of O. ficus-indica, in comparison with cultivar “Gialla”, and also evaluate its potential use as a feed for ruminan...
Bone is a dynamic tissue that is maintained by continuous renewal. An imbalance in bone resorptio... more Bone is a dynamic tissue that is maintained by continuous renewal. An imbalance in bone resorption and bone formation can lead to a range of disorders, such as osteoporosis. The receptor activator of NF-κB (RANK)-RANK-ligand (RANKL) pathway plays a major role in bone remodeling. Here, we investigated the effect of mutations at position I248 in the DE-loop of murine RANKL on the interaction of RANKL with RANK, and subsequent activation of osteoclastogenesis. Two single mutants, RANKL I248Y and I248K, were found to maintain binding and have the ability to reduce wild-type RANKL-induced osteoclastogenesis. The generation of RANK-antagonists is a promising strategy for the exploration of new therapeutics against osteoporosis.
Inferior vena cava leiomyosarcoma is a very rare tumor, accounting for only 0.5% of all soft tiss... more Inferior vena cava leiomyosarcoma is a very rare tumor, accounting for only 0.5% of all soft tissue sarcomas. As the other leyomiosarcomas of vascular origin, they have a poor prognosis, and radical resection with surgical margins free of tumor is the only potentially curative treatment. We present a case of a 46 year-old woman with metastatic inferior vena cava leiomyosarcoma who progressed after anthracyclines and ifosfamide and achieved a complete and sustained response with trabectedin. Beyond progression, the patient started third line treatment with pazopanib. A brief review of literature is also given. This case supports the efectiveness of a recent therapeutic agent, with an impressive progression-free survival in a recurrent metastatic inferior vena cava leiomyosarcoma.
Miguel Bombarda e as singularidades de uma época: 1851-1910, 2006
nada de SuStoS: repreSentaçõeS literáriaS da CiênCia e da mediCina. Nada de sustos: um professor ... more nada de SuStoS: repreSentaçõeS literáriaS da CiênCia e da mediCina. Nada de sustos: um professor de literatura também pode dar o seu contributo, limitado embora, a um congresso em que se discute a ciência e a medicina. Aceite-se, para que esse contributo possa acontecer, que à literatura nada escapa; nos mundos que constrói-e particularmente nos mundos ficcionais-tudo cabe, porque neles está a vida que a representação literária modela e refigura, recorrendo para tal aos instrumentos e aos procedimentos que por natureza (natureza estética, entenda-se) são os seus: personagens, intrigas, imagens, tempos narrativos, metáforas poéticas, pontos de vista, estratégias de narração, etc. De certa forma, o ponto de partida que escolhi e que está no título corresponde ao lugar de serena ponderação que é o de uma personagem queirosiana, médico e, por isso, aqui bem enquadrado, até mesmo por ser contemporâneo de Miguel Bombarda, patrono deste congresso. Cito um passo aparentemente inócuo d'O Crime do Padre Amaro: Amélia todo o dia pensou naquela história. De noite veio-lhe uma grande febre, com sonhos espessos, em que dominava a figura do frade franciscano, na sombra do órgão da Sé de Évora. (…) Ao outro dia a febre acalmou. O doutor Gouveia tranquilizou a S. Joaneira com uma simples palavra:-Nada de sustos, minha rica senhora, são os quinze anos da rapariga. Hão-de lhe vir amanhã as vertigens e os enjoos… Depois acabou-se. Temo-la mulher. A S. Joaneira compreendeu.-Esta rapariga tem o sangue vivo e há-de ter as paixões fortes! acrescentou o velho prático, sorrindo e sorvendo a sua pitada. 1
Partindo da análise da evolução dos meios de comunicação destacamos o significado do seu impacto ... more Partindo da análise da evolução dos meios de comunicação destacamos o significado do seu impacto no quotidiano daqueles que vivem no seio das sociedades ditas mediáticas, como a nossa, em que os media penetram todas as dimensões sociais: a economia, a política, a educação, mas também os valores, as atitudes, os costumes e os hábitos. São fornecidos alguns dados indicativos sobre o uso dos meios de modo a esclarecer o seu poder para se instituírem como uma força determinante da socialização dos indivíduos. A discussão do tema serve para derivar recomendações sobre o tipo de consumo que parece ser adequado a diferentes grupos etários, tendo em conta certos critérios desenvolvimentais.
There is strong interest in creating an enzyme that can deacylate natural cephalosporins such as ... more There is strong interest in creating an enzyme that can deacylate natural cephalosporins such as cephalosporin C in order to efficiently acquire the starting compound for the industrial production of semisynthetic cephalosporin antibiotics. In this study, the active site of the glutaryl acylase from Pseudomonas SY-77 was randomized rationally. Several mutations that were found in previous studies to enhance the activity of the enzyme towards adipyl-7-aminodesacetoxycephalosporanic acid (ADCA) and cephalosporin C have now been combined, and libraries have been made in which random amino acid substitutions at these positions are joined. The mutants were expressed in a leucine-deficient Escherichia coli strain and subjected to growth selection with adipyl-leucine or amino-adipyl-leucine as sole leucine source. The mutants growing on these media were selected and purified, and their hydrolysis activities towards adipyl-7-ADCA and cephalosporin C were tested. Several mutants with highly improved activities towards the desired substrates were found in these rationally randomized libraries. The best mutant was selected from a library of totally randomized residues: 178, 266, and 375. This mutant comprises two mutations, Y178F + F375H, which synergistically improve the catalytic efficiency towards adipyl-7-ADCA 36-fold. The activity of this mutant towards adipyl-7-ADCA is 50% of the activity of the wild-type enzyme towards the preferred substrate glutaryl-7-aminocephalosporanic acid, and therefore the characteristics of this mutant approach those needed for industrial application.
Proceedings of the National Academy of Sciences, 2014
Significance Resistance toward commonly used antibiotics is becoming a serious issue in the fight... more Significance Resistance toward commonly used antibiotics is becoming a serious issue in the fight against bacterial pathogens. One promising strategy lies in the interference of bacterial quorum sensing by the hydrolysis of the signaling molecules. In this study, we present a structure-aided computational design approach to alter the substrate specificity of the quorum-quenching acylase PvdQ. Introduction of two point mutations in residues lining the active site led to a switch in substrate specificity, rendering the enzyme highly active toward C8-HSL and thereby reducing virulence caused by Burkholderia cenocepacia . Thus, this work not only provides a structural insight into the substrate specificity of quorum-quenching acylases but also indicates their potential in the fight against specific bacterial pathogens.
The accelerated expansion of the universe has now been confirmed by several independent observati... more The accelerated expansion of the universe has now been confirmed by several independent observations including those of high redshift type Ia supernovae, and the cosmic microwave background combined with the large scale structure of the universe. Another way of presenting this kinematic property of the universe is to postulate the existence of a new and exotic entity, with negative pressure, the dark energy (DE). In spite of observationally well established, no single theoretical model provides an entirely compelling framework within which cosmic acceleration or DE can be understood. At present all existing observational data are in agreement with the simplest possibility that the cosmological constant be a candidate for DE. This case is internally self-consistent and noncontradictory. The extreme smallness of the cosmological constant expressed in either Planck, or even atomic units means only that its origin is not related to strong, electromagnetic, and weak interactions. Althoug...
European Spallation Source (ESS), the next-generation neutron source facility, is expected to pro... more European Spallation Source (ESS), the next-generation neutron source facility, is expected to produce an immense amount of data. Various working groups mostly associated with the EU project BrightnESS aim at developing solutions for its data-intensive challenges. The real-time data management and aggregation is among the top priorities. The Apache KAFKA framework will be the base for ESS real-time distributed data streaming. One of the major challenges is the simulation of data streams from experimental data generation to data analysis and storage. This presentation outlines a simulation approach based on the DonkiOrchestra data acquisition and experiment control framework, re-purposed as a data streaming simulation system compatible with the ESS-KAFKA infrastructure.
RODRIGUES, A. M., F. I. PITACAS, C. M. G. REIS and M. BLASCO, 2016. Nutritional value of Opuntia ... more RODRIGUES, A. M., F. I. PITACAS, C. M. G. REIS and M. BLASCO, 2016. Nutritional value of Opuntia ficusindica cladodes from Portuguese ecotypes. Bulg. J. Agric. Sci., 22: 40–45 The use of Opuntia ficus-indica cladodes as a forage for ruminants has been very important in the semi-arid and arid regions of the world. O. ficus-indica cladodes can be fed to small ruminants especially in periods of the year when there is low quality and quantity of pasture. In Mediterranean regions like South of Portugal during the rainy season the availability of pasture is quantitatively and qualitatively satisfactory, but in critical times of the year the shortage and low nutritive value of forages causes decreased productivity in the ruminant’s production of milk and meat. The aim of this study was to evaluate the nutritional profile of the cladodes from five different Portuguese ecotypes of O. ficus-indica, in comparison with cultivar “Gialla”, and also evaluate its potential use as a feed for ruminan...
Bone is a dynamic tissue that is maintained by continuous renewal. An imbalance in bone resorptio... more Bone is a dynamic tissue that is maintained by continuous renewal. An imbalance in bone resorption and bone formation can lead to a range of disorders, such as osteoporosis. The receptor activator of NF-κB (RANK)-RANK-ligand (RANKL) pathway plays a major role in bone remodeling. Here, we investigated the effect of mutations at position I248 in the DE-loop of murine RANKL on the interaction of RANKL with RANK, and subsequent activation of osteoclastogenesis. Two single mutants, RANKL I248Y and I248K, were found to maintain binding and have the ability to reduce wild-type RANKL-induced osteoclastogenesis. The generation of RANK-antagonists is a promising strategy for the exploration of new therapeutics against osteoporosis.
Inferior vena cava leiomyosarcoma is a very rare tumor, accounting for only 0.5% of all soft tiss... more Inferior vena cava leiomyosarcoma is a very rare tumor, accounting for only 0.5% of all soft tissue sarcomas. As the other leyomiosarcomas of vascular origin, they have a poor prognosis, and radical resection with surgical margins free of tumor is the only potentially curative treatment. We present a case of a 46 year-old woman with metastatic inferior vena cava leiomyosarcoma who progressed after anthracyclines and ifosfamide and achieved a complete and sustained response with trabectedin. Beyond progression, the patient started third line treatment with pazopanib. A brief review of literature is also given. This case supports the efectiveness of a recent therapeutic agent, with an impressive progression-free survival in a recurrent metastatic inferior vena cava leiomyosarcoma.
Miguel Bombarda e as singularidades de uma época: 1851-1910, 2006
nada de SuStoS: repreSentaçõeS literáriaS da CiênCia e da mediCina. Nada de sustos: um professor ... more nada de SuStoS: repreSentaçõeS literáriaS da CiênCia e da mediCina. Nada de sustos: um professor de literatura também pode dar o seu contributo, limitado embora, a um congresso em que se discute a ciência e a medicina. Aceite-se, para que esse contributo possa acontecer, que à literatura nada escapa; nos mundos que constrói-e particularmente nos mundos ficcionais-tudo cabe, porque neles está a vida que a representação literária modela e refigura, recorrendo para tal aos instrumentos e aos procedimentos que por natureza (natureza estética, entenda-se) são os seus: personagens, intrigas, imagens, tempos narrativos, metáforas poéticas, pontos de vista, estratégias de narração, etc. De certa forma, o ponto de partida que escolhi e que está no título corresponde ao lugar de serena ponderação que é o de uma personagem queirosiana, médico e, por isso, aqui bem enquadrado, até mesmo por ser contemporâneo de Miguel Bombarda, patrono deste congresso. Cito um passo aparentemente inócuo d'O Crime do Padre Amaro: Amélia todo o dia pensou naquela história. De noite veio-lhe uma grande febre, com sonhos espessos, em que dominava a figura do frade franciscano, na sombra do órgão da Sé de Évora. (…) Ao outro dia a febre acalmou. O doutor Gouveia tranquilizou a S. Joaneira com uma simples palavra:-Nada de sustos, minha rica senhora, são os quinze anos da rapariga. Hão-de lhe vir amanhã as vertigens e os enjoos… Depois acabou-se. Temo-la mulher. A S. Joaneira compreendeu.-Esta rapariga tem o sangue vivo e há-de ter as paixões fortes! acrescentou o velho prático, sorrindo e sorvendo a sua pitada. 1
Partindo da análise da evolução dos meios de comunicação destacamos o significado do seu impacto ... more Partindo da análise da evolução dos meios de comunicação destacamos o significado do seu impacto no quotidiano daqueles que vivem no seio das sociedades ditas mediáticas, como a nossa, em que os media penetram todas as dimensões sociais: a economia, a política, a educação, mas também os valores, as atitudes, os costumes e os hábitos. São fornecidos alguns dados indicativos sobre o uso dos meios de modo a esclarecer o seu poder para se instituírem como uma força determinante da socialização dos indivíduos. A discussão do tema serve para derivar recomendações sobre o tipo de consumo que parece ser adequado a diferentes grupos etários, tendo em conta certos critérios desenvolvimentais.
There is strong interest in creating an enzyme that can deacylate natural cephalosporins such as ... more There is strong interest in creating an enzyme that can deacylate natural cephalosporins such as cephalosporin C in order to efficiently acquire the starting compound for the industrial production of semisynthetic cephalosporin antibiotics. In this study, the active site of the glutaryl acylase from Pseudomonas SY-77 was randomized rationally. Several mutations that were found in previous studies to enhance the activity of the enzyme towards adipyl-7-aminodesacetoxycephalosporanic acid (ADCA) and cephalosporin C have now been combined, and libraries have been made in which random amino acid substitutions at these positions are joined. The mutants were expressed in a leucine-deficient Escherichia coli strain and subjected to growth selection with adipyl-leucine or amino-adipyl-leucine as sole leucine source. The mutants growing on these media were selected and purified, and their hydrolysis activities towards adipyl-7-ADCA and cephalosporin C were tested. Several mutants with highly improved activities towards the desired substrates were found in these rationally randomized libraries. The best mutant was selected from a library of totally randomized residues: 178, 266, and 375. This mutant comprises two mutations, Y178F + F375H, which synergistically improve the catalytic efficiency towards adipyl-7-ADCA 36-fold. The activity of this mutant towards adipyl-7-ADCA is 50% of the activity of the wild-type enzyme towards the preferred substrate glutaryl-7-aminocephalosporanic acid, and therefore the characteristics of this mutant approach those needed for industrial application.
Proceedings of the National Academy of Sciences, 2014
Significance Resistance toward commonly used antibiotics is becoming a serious issue in the fight... more Significance Resistance toward commonly used antibiotics is becoming a serious issue in the fight against bacterial pathogens. One promising strategy lies in the interference of bacterial quorum sensing by the hydrolysis of the signaling molecules. In this study, we present a structure-aided computational design approach to alter the substrate specificity of the quorum-quenching acylase PvdQ. Introduction of two point mutations in residues lining the active site led to a switch in substrate specificity, rendering the enzyme highly active toward C8-HSL and thereby reducing virulence caused by Burkholderia cenocepacia . Thus, this work not only provides a structural insight into the substrate specificity of quorum-quenching acylases but also indicates their potential in the fight against specific bacterial pathogens.
The accelerated expansion of the universe has now been confirmed by several independent observati... more The accelerated expansion of the universe has now been confirmed by several independent observations including those of high redshift type Ia supernovae, and the cosmic microwave background combined with the large scale structure of the universe. Another way of presenting this kinematic property of the universe is to postulate the existence of a new and exotic entity, with negative pressure, the dark energy (DE). In spite of observationally well established, no single theoretical model provides an entirely compelling framework within which cosmic acceleration or DE can be understood. At present all existing observational data are in agreement with the simplest possibility that the cosmological constant be a candidate for DE. This case is internally self-consistent and noncontradictory. The extreme smallness of the cosmological constant expressed in either Planck, or even atomic units means only that its origin is not related to strong, electromagnetic, and weak interactions. Althoug...
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