Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane

p53 is a transcription factor that induces growth arrest or apoptosis in response to cellular stress. To identify new p53-inducible proapoptotic genes, we compared, by differential display, the expression of genes in spleen or thymus of normal and p53 nullizygote mice after γ-irradiation of whole animals. We report the identification and characterization of human and mouse Scotin homologues, a novel gene directly transactivated by p53. The Scotin protein is localized to the ER and the nuclear membrane. Scotin can induce apoptosis in a caspase-dependent manner. Inhibition of endogenous Scotin expression increases resistance to p53-dependent apoptosis induced by DNA damage, suggesting that Scotin plays a role in p53-dependent apoptosis. The discovery of Scotin brings to light a role of the ER in p53-dependent apoptosis

A VALIDATED STABILITY INDICATING RP-HPLC METHOD FOR ESTIMATION OF TOLFENAMIC ACID IN PRESENCE OF ITS PHARMACOPOEIAL IMPURITIES

Objective: The proposed research work was conducted to develop a single reverse-phase high-performance chromatography (RP-HPLC) method capable of separating two Pharmacopoeial related impurities as well as degradation product of Tolfenamic acid (TA). The drug was subjected to various stress conditions recommended under ICH Q1A (R2) guidelines. Methods: The desired separation of two Pharmacopoeial impurities and one degradant generated under oxidative stress was carried out using Sunfire ODS C-18 (250 x 4.6 mm, 5 µm) column maintained at 40 °C. Isocratic elution was carried out using acetonitrile and ammonium dihydrogen orthophosphate buffer (10 mmol, pH 2.5) in the ratio of 80:20 v/v. The detection was carried out at 205 nm using flow rate of 1 ml/min. The developed method was validated as per ICH Q2 (R1) guidelines for specificity, linearity, accuracy, precision, Limit of detection (LOD), Limit of Quantification (LOQ) and robustness. Results: Linearity response of TA was found at a concentration range of 10-100µg/ml, with a correlation coefficient of 0.9987. The Pharmacopoeial impurity A and impurity B showed linearity results at concentration of 0.1-1µg/ml, with correlation coefficient of 0.9984 for Impurity A and 0.9989 for Impurity B. The % recovery during accuracy studies for TA and the two impurities were within the acceptance range of 95-105%. LOD and LOQ for TA were found to be 4.561µg/ml and 133.771µg/ml respectively. For impurity A, LOD and LOQ were found to be 0.035 µg/ml and 0.106 µg/ml and for Impurity B, LOD and LOQ were 0.042 µg/ml and 0.128 µg/ml. With slight variation of organic phase in mobile phase and flow rate the method exhibited good robustness. Under forced degradation studies the drug was found stable under hydrolytic, photolytic and thermal stress conditions, but was found susceptible for degradation under oxidative stress with appearance of a degradant peak. From on the RRT values of Pharmacopoeial impurities and the formed degradant it was inferred that the developed method is selective for the drug in the presence of impurities or degradants. Conclusion: The developed stability-indicating method is found to be simple, rapid, accurate, precise and robust as compared to other proposed methods while determining TA in presence of its Pharmacopoeial impurities and degradation products. Hence the developed method can be used for analysis of stability samples of TA in presence of its related impurities

Numerical experiments with a continuous L_2-exponential merit function for semi-infinite programming

Here, we present some numerical experiments with a reduction method for solving nonlinear semi-infinite programming (SIP) problems. The method relies on a line search technique to ensure a sufficient decrease of a L_2-exponential merit function. The proposed merit function is continuous for SIP and improves the algorithm efficiency when compared with other previously tested merit functions. A comparison with other reduction methods is also included.Algoritmi Research CenterFundação para a Ciência e a Tecnologia (FCT) - POCl/MAT/58957/200

Avaliação de impacto ambiental em estabelecimentos de pecuária de leite com manejo orgânico e convencional.

Este trabalho teve por objetivo avaliar o impacto ambiental da pecuária de leite convencional e orgânica em dois estabelecimentos representativos do município de Serra Negra, SP, utilizando o sistema APOIA ? Novo Rural. A pecuária orgânica apresentou um índice geral de impacto ambiental (0,77)superior ao da pecuária convencional (0,67), sendo que as dimensões Ecologia da Paisagem, Qualidade da Água, Valores Econômicos e Gestão e Administração foram as que melhor qualificaram essa atividade em termos de sua contribuição para o desenvolvimento local sustentável

Identificação, caracterização e inserção no mercado de produtos orgânicos na região da Barreira do Andirá.

A pesquisa objetivou caracterizar as principais cadeias de produtos orgânicos da agricultura familiar e sua inserção no mercado. Foi realizada na comunidade Barreira do Andirá, município de Barreirinha - AM e poderá vir a subsidiar propostas de desenvolvimento local sustentável. Como ferramenta de pesquisa utilizou-se o método estudo de caso. Identificando-se duas importantes cadeias produtivas: a da mandioca e a do guaraná e, a importância da organização social para alcançar o desenvolvimento rural com base na agroecologia

On a reduction line search filter method for nonlinear semi-Infinite programming problems

In this paper, a reduction-type method combined with a line search filter method to solve nonlinear semi-infinite programming problems is presented. The algorithm uses the simulated annealing method equipped with a function stretching technique to compute the maximizers of the constraint, and a penalty technique to solve the reduced finite optimization problem. The filter method is used as an alternative to merit functions to guarantee convergence from poor starting points. Preliminary numerical results with a problems test set are shown.Fundação para a Ciência e a Tecnologia (FCT) - POCI/MAT/58957/2004Algoritmi R & D Centr

A hyperbolic penalty filter method for semi-infinite programming

This paper presents a new reduction-type method for solving semi-infinite programming problems, where the multi-local optimization is carried out with a sequential simulated annealing algorithm, and the finite reduced problem is solved by a penalty technique based on an hyperbolic function. Global convergence is ensured by a line search filter method. Numerical experiments with a set of known problems show that the algorithm is promising