Por “Estudio multicéntrico no intervencional en pacientes con artritis reumatoidea tratados con tocilizumab”

Estimado Editor: uno de los paradigmas en el tratamiento de la Artritis Reumatoidea (AR) ha sido la introducción de los agentes biológicos.

Projeto de uma fonte chaveada baseada no conversor push-pull

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. Engenharia Elétrica.Este trabalho apresenta uma metodologia de projeto de fontes chaveadas baseadas no conversor Push-Pull. Além disso, exploram-se técnicas de controle com o intuito de garantir que as especificações de saída sejam satisfeitas. Desse modo, o trabalho é composto por três capítulos, os quais analisam os principais circuitos contidos neste projeto. Devido a simplicidade do circuito retificador, escolheu-se omiti-lo do texto, entretanto seu dimensionamento é apresentado no Apêndice A. No Capítulo 2 é analisado detalhadamente o circuito do conversor Push-Pull, cuja função é controlar o fluxo de energia entre a fonte e a carga. Ao longo do capítulo são descritas as etapas de operação, o equacionamento, as formas de onda das grandezas presentes no circuito e principalmente seus os valores máximo, médio, eficaz. O conversor é dimensionado e todos estes valores são calculados. Por fim, para validar o dimensionamento, o conversor é simulado em malha aberta considerando todos os parâmetros calculados. No Capítulo 3, é feita a especificação de componentes. Ela consiste, essencialmente, em definir uma sugestão de quais componentes disponíveis no mercado poderiam utilizados para implementar um protótipo deste projeto. Para isso, será necessário realizar o cálculo de perdas e o cálculo térmico. No Capítulo 4, é realizado todo o projeto de controle do sistema. Além disso, é definida a estratégia de controle a ser utilizada para este sistema e principalmente qual topologia de controlador será empregada. A escolha da melhor estratégia de controle é um dos itens mais importantes do trabalho, pois proporciona algumas propriedades desejadas ao sistema, tais como, imunidade a perturbações na tensão de entrada, na tensão de referência e imunidades a variações de carga. Finalmente, no Capítulo 5 são realizadas as considerações finais do trabalho apresentando os pontos principais, as escolhas de projeto, suas vantagens e desvantagens, e possíveis melhorias a serem feitas.This work presents a methodology for the design of a switched-mode power supply based on the Push-Pull power converter. In addition, control techniques are explored to ensure the output specifications. Thereby, this work is composed by three chapters and in each of them is analysed the main components of the block diagram that model the power supply. Due to the simplicity of the rectifier circuit, it was decided to omit it from the main text, although the calculations needed to design this circuit are presented in Appendix A. In Chapter 2, the Push-Pull power converter circuit is studied in detail, especially because of the main function of this circuit, which is to control the flow of energy between source and load. Throughout the chapter the stages of operation of the power converter, main equations and waveforms are presented in detail as is the peak, average and RMS values. The entire power converter is designed and all of these magnitudes are calculated. Next, to ensure that the power converter was analysed correctly, it is simulated in open loop conditions using the paramaters previously calculated. In Chapter 3, is presented the specifications of the components that could be used in this project which is basicaly a suggestion of which components available in the market could be used to implement a prototype of this power supply. To achieve this, it is necessary to perform the power losses and termal calculations. In Chapter 4, the control loop is closed and the compensator design calculations are done. At this stage, the main points addressed are defining a control loop strategy and mainly which compensator type is going to be designed. Choosing the best control loop strategy is the most important item of this text because the closed loop provides the entire power supply system some interesting properties like input voltage, output load and reference voltage pertubations rejection. At Chapter 5, the final considerations are presented as well as the benefits and disadvantages of the main design choices. Also, some possible improvements to the models and circutry used are suggested

Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

Background: This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7) in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13) did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12). The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere) and the affectation (or not) of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods: The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories), Digits span (WISC-R verbal scale) and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74) years from surgery in CE group and at 6.47 (SD = 2.77) in CE+ group. Results: The Medulloblastoma group showed severe executive deficit (</= 1.5 SD below normal mean) in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category) and moderate to slight deficit in Stroop (word and colour) tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables. Conclusion: Results suggest a differential prefrontal-like deficit due to cerebellar lesions and/or cerebellar-frontal diaschisis, as indicate the results in astrocytoma group (without treatments), that also can be generated and/or increased by treatments in the medulloblastoma group. The need for differential rehabilitation strategies for specific clinical groups is remarked. The results are also discussed in the context of the Cerebellar Cognitive Affective Syndrome.4:18; pags: 1-16 doi: 10.1186/1744-9081-4-18

Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities

Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton. In this work, we developed the hemisynthesis of trichodermin and trichodermol derivatives in order to evaluate their antimicrobial and cytotoxic activities and to study the chemo-modulation of their bioactivity. Some derivatives with a short chain at the C-4 position displayed selective antimicrobial activity against Candida albicans and they showed MIC values similar to those displayed by trichodermin. It is important to highlight the cytotoxic selectivity observed for compounds 9, 13, and 15, which presented average IC50 values of 2 g/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes)

Targeted Inactivation of the mecB Gene, Encoding Cystathionine-γ-Lyase, Shows that the Reverse Transsulfuration Pathway Is Required for High-Level Cephalosporin Biosynthesis inAcremonium chrysogenum C10 but Not for Methionine Induction of the Cephalosporin Genes

[EN] Targeted gene disruption efficiency in Acremonium chrysogenum was increased 10-fold by applying the double-marker enrichment technique to this filamentous fungus. Disruption of themecB gene by the double-marker technique was achieved in 5% of the transformants screened. Mutants T6 and T24, obtained by gene replacement, showed an inactive mecB gene by Southern blot analysis and no cystathionine-γ-lyase activity. These mutants exhibited lower cephalosporin production than that of the control strain, A. chrysogenum C10, in MDFA medium supplemented with methionine. However, there was no difference in cephalosporin production between parental strain A. chrysogenum C10 and the mutants T6 and T24 in Shen's defined fermentation medium (MDFA) without methionine. These results indicate that the supply of cysteine through the transsulfuration pathway is required for high-level cephalosporin biosynthesis but not for low-level production of this antibiotic in methionine-unsupplemented medium. Therefore, cysteine for cephalosporin biosynthesis in A. chrysogenum derives from the autotrophic (SH2) and the reverse transsulfuration pathways. Levels of methionine induction of the cephalosporin biosynthesis gene pcbC were identical in the parental strain and the mecB mutants, indicating that the induction effect is not mediated by cystathionine-γ-lyase.SIThis work was supported by a grant of the CICYT (BIO97-0289-C02-01). We thank A. Paszewski for providing Aspergillus nidulansstrains M63 and C47 and M. Mediavilla, B. Martı́n, R. Barrientos, and M. Corrales for excellent technical assistance

Algorithms applied for monitoring pelagic Sargassum

Massive arrivals of pelagic Sargassum to the coasts of several countries in the Atlantic Ocean began in 2011. Monitoring the abundance and distribution of Sargassum in the ocean and along the coasts is necessary to understand the phenomena better and develop forecasting products and management protocols. Most Sargassum monitoring has been conducted in the open ocean through traditional remote sensing techniques. However, since the most significant ecologic and socioeconomic impacts occur on the coasts, it is necessary to monitor these macroalgae on nearshore waters and beaches. This manuscript reviews the remote sensing algorithms used in Sargassum observation reported in the last 17 years in more than sixty high-impact scientific publications. The discussion regarding the evolution of the methodologies used for monitoring these macroalgae allowed us to conclude that the synergy generated by incorporating new disciplines like artificial intelligence and citizen science has positively impacted the development of this field. Additionally, the current state-of-the-art methods, the fundamental challenges, and the directions for future research are also discussed

Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities

[EN] Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton. In this work, we developed the hemisynthesis of trichodermin and trichodermol derivatives in order to evaluate their antimicrobial and cytotoxic activities and to study the chemo-modulation of their bioactivity. Some derivatives with a short chain at the C-4 position displayed selective antimicrobial activity against Candida albicans and they showed MIC values similar to those displayed by trichodermin. It is important to highlight the cytotoxic selectivity observed for compounds 9, 13, and 15, which presented average IC50 values of 2 µg/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes)S

Deep Sequencing of Target Linkage Assay-Identified Regions in Familial Breast Cancer: Methods, Analysis Pipeline and Troubleshooting

Background: The classical candidate-gene approach has failed to identify novel breast cancer susceptibility genes. Nowadays, massive parallel sequencing technology allows the development of studies unaffordable a few years ago. However, analysis protocols are not yet sufficiently developed to extract all information from the huge amount of data obtained. Methodology/Principal Findings: In this study, we performed high throughput sequencing in two regions located on chromosomes 3 and 6, recently identified by linkage studies by our group as candidate regions for harbouring breast cancer susceptibility genes. In order to enrich for the coding regions of all described genes located in both candidate regions, a hybrid-selection method on tiling microarrays was performed. Conclusions/Significance: We developed an analysis pipeline based on SOAP aligner to identify candidate variants with a high real positive confirmation rate (0.89), with which we identified eight variants considered candidates for functiona