In silico prediction of human carboxylesterase-1 (hCES1) metabolism combining docking analyses and MD simulations.

Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted in developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas little has been done to predict the hydrolytic activity of human hydrolases. The present study was undertaken to develop a computational approach able to predict the hydrolysis of novel esters by human carboxylesterase hCES1. The study involves both docking analyses of known substrates to develop predictive models, and molecular dynamics (MD) simulations to reveal the in situ behavior of substrates and products, with particular attention being paid to the influence of their ionization state. The results emphasize some crucial properties of the hCES1 catalytic cavity, confirming that as a trend with several exceptions, hCES1 prefers substrates with relatively smaller and somewhat polar alkyl/aryl groups and larger hydrophobic acyl moieties. The docking results underline the usefulness of the hydrophobic interaction score proposed here, which allows a robust prediction of hCES1 catalysis, while the MD simulations show the different behavior of substrates and products in the enzyme cavity, suggesting in particular that basic substrates interact with the enzyme in their unprotonated form.

Adubação N-P-K e o desenvolvimento, produtividade e qualidade dos frutos do abacaxi 'gold' (MD-2)

O abacaxi Gold (MD-2) tem atraído interesse no Brasil, visando à exportação. No entanto, há poucas informações científicas no País sobre o manejo nutricional dessa cultivar. O presente trabalho teve por objetivo determinar o efeito da adubação com N, P e K no estado nutricional da planta, no desenvolvimento, na produtividade e na qualidade dos frutos do abacaxi MD-2. Foram avaliados os efeitos de cinco doses de N, cinco de P2O5 e cinco de K 2O sobre as características de crescimento da folha D e do fruto, bem como sobre os teores de N, P e K das folhas D e as características de qualidade do fruto. Concluiu-se que as maiores produtividade e massa de fruto foram obtidas com a aplicação de 650,6 kg ha-1 de N e 735,9 kg ha-1 de K2O, correspondendo a 12,7 e 14,4 g/planta de N e K2O, respectivamente. Nesse caso, a indução floral deve ser recomendada quando a folha D apresentar comprimento > 75,5 cm. Os valores das características de qualidade do fruto diminuíram com a aplicação de N e aumentaram com a adição de P e K, sendo que as doses máximas de 205,8 kg ha-1 de P2O5 e 703,4 kg ha-1 de K2O corresponderam a 4,01 e 13,7 g/planta de N e K2O, respectivamente.

Dosimetria dos cones radiocirúrgicos Radionics de diâmetros de 5 mm a 50 mm para um feixe de 6 MV de um acelerador linear Mevatron MD digital

Os parâmetros dosimétricos de um feixe de raios X de pequeno diâmetro para um sistema de radiocirurgia comercial foram medidos em água com um detector de diodo de Si do tipo p. As razões tecido-máximo, o fator de espalhamento total e os perfis dos feixes a profundidades de 5 e 10 cm foram medidos para 17 feixes de diâmetros circulares de 5 mm a 50 mm, em incrementos de 2,5 mm. Os fatores de espalhamento totais caíram lentamente, de 0,947 para 0,888 entre os cones de 50 mm e 12,5 mm de diâmetro (variação de 7%); para os cones entre 10 mm e 5 mm de diâmetro, esta queda foi bem maior, de 0,854 para 0,666 (variação de 28%). Os valores obtidos para a relação tecido-máximo são consistentes com dados publicados. Os perfis dos feixes foram medidos nas direções x e y, e estão dentro de 0,2 mm para todos os cones entre as duas direções. A medida da largura à meia-altura se encontra dentro de 1 mm com o diâmetro nominal dos cones.

Quantificação do linalol no óleo essencial da Aniba duckei Korstermans utilizando uma nova coluna capilar POLYH4-MD em Cromatografia Gasosa

In the present work a polyurethane polymer derived from castor oil was used as stationary phase for capillary gas chromatography. The polymer was obtained by reaction of hydroxylated compound and isocynate (NCO), forming urethane. Columns of 7 m x 0,25 mm were then coated with this stationary phase (film thickness of 0,25 µm) using static coating method. The Grob test was also performed. Samples of essential oil of the Aniba duckei Korstermans was then analysed in POLYH4-MD capillary column in order to evaluate its chromatographic perfomance. The linalool was found to be the major component and has been used as compound of departure for many important syntheses. Results show that the experimental columns give higher resolution and can be employed for analysis of essentials oils.

An MD-PhD program in Brazil: students’ concepts of science and of common sense

In 1995, a pioneering MD-PhD program was initiated in Brazil for the training of medical scientists in experimental sciences at the Federal University of Rio de Janeiro. The program’s aim was achieved with respect to publication of theses in the form of papers with international visibility and also in terms of fostering the scientific careers of the graduates. The expansion of this type of program is one of the strategies for improving the preparation of biomedical researchers in Brazil. A noteworthy absence of interest in carrying out clinical research limits the ability of young Brazilian physicians to solve biomedical problems. To understand the students’ views of science, we used qualitative and quantitative triangulation methods, as well as participant observation to evaluate the students’ concepts of science and common sense. Subjective aspects were clearly less evident in their concepts of science. There was a strong concern about "methodology", "truth" and "usefulness". "Intuition", "creativity" and "curiosity" were the least mentioned thematic categories. Students recognized the value of intuition when it appeared as an explicit option but they did not refer to it spontaneously. Common sense was associated with "consensus", "opinion" and ideas that "require scientific validation". Such observations indicate that MD-PhD students share with their senior academic colleagues the same reluctance to consider common sense as a valid adjunct for the solution of scientific problems. Overcoming this difficulty may be an important step toward stimulating the interest of physicians in pursuing experimental research.

Speech of Com. Jesse Duncan Elliott, U.S.N. delivered in Hagerstown, Md. on 14th November, 1843.-

Published by the Committee of Arrangement of Washington County, Maryland.

Speech of Com. Jesse Duncan Elliott, U.S.N. delivered in Hagerstown, Md. on 14th November, 1843

Published by the Committee of Arrangement of Washington County, Maryland Printed by G.B. Zeiber and Co.

Estudi de les obres del Museo del Prado al MD'A: Estudi obres 2005 [versió comprimida]

Es presenta la primera part de l'Estudi del fons pictòric, en la major part, d'època barroca que procedeix del Museo del Prado. Fons dipositat a l'Antic Museu Provincial per Reial Ordre entre 1880 i 1882