Functional genetic dropout screens and in vivo validation of candidate therapeutic targets using mouse mammary tumoroids

We have previously developed 3D tumoroids derived from genetically engineered mouse models (GEMMs) of BRCA1/2-deficient breast cancer. Here, we describe how to genetically modify tumoroids, use them for functional genetic dropout screens, and carry out orthotopic transplantation of modified tumoroids. The purpose of this protocol is to screen for therapeutic targets and allow rapid and straightforward in vivo validation of the candidate targets

Produzindo liberdade, escravidão e normas no Império português

Resenha do livro:  PINHEIRO, Fernanda Domingos. Em defesa da liberdade: libertos, coartados e livres de cor nos tribunais do Antigo Regime português (Mariana e Lisboa, 1720-1819). Belo Horizonte: Fino Traço Editora, 2018.Book review:  PINHEIRO, Fernanda Domingos. Em defesa da liberdade: libertos, coartados e livres de cor nos tribunais do Antigo Regime português (Mariana e Lisboa, 1720-1819). Belo Horizonte: Fino Traço Editora, 2018

Esclavos y tierras entre posesión y títulos

This book examines the social construction of legal relations between people and things in Brazil during the 19th century through the analysis of court cases discussing dominion and possession over slaves and land. The chapters address topics such as the role of social recognition in situations of possession, the process of delegitimizing acts of land usage from indigenous peoples, dependent persons and women, and the widespread illegal acquisition of slaves and land

La misoginia como arma política: cómo las fotografías publicadas en la prensa ayudaron a destruir la imagen de la presidenta de Brasil, Dilma Rousseff

Fac. de Ciencias Políticas y SociologíaFALSEunpu

Fatores associados à implantação de programas de prevenção ao uso de drogas nas escolas

OBJECTIVE To analyze if characteristics of managers, schools, and curriculum are associated with the implementation of programs for drug abuse prevention in elementary and high schools. METHODS Cross-sectional study, with random sample of 263 school managers. Data were collected between 2012 and 2013 by a program that sends forms via internet. A closed self-filling questionnaire was applied online. Statistical analysis included Chi-square tests and logistic regression models. The outcome variable was the presence of program for drug abuse prevention inserted in the daily life and educational program of the school. The explanatory variables were divided into: demographic data of the manager; characteristics of the school and of the curriculum; health education; and drug use in the school. RESULTS We found that 42.5% (95%CI 36.1–49.1) of the evaluated schools had programs for drug abuse prevention. With the multiple logistic regression model, we observed that the more time the manager has worked with education, the chance of the school having a program increased at about 4.0%. Experimenting with innovative teaching techniques also increased at about six times the chance of the school developing a program for drug abuse prevention. The difficulties in the implementation of the programs were more present in state and municipal schools, when compared with private schools, due to, for instance: lack of teaching materials, lack of money, and competing demands for teaching other subjects. CONCLUSIONS The implementation of programs for drug abuse prevention in the city of Sao Paulo is associated with the experience of the manager in education and with the teaching strategies of the school.OBJETIVO Analisar se características dos dirigentes, das escolas e do currículo escolar estão associadas à implantação de programas de prevenção ao uso de drogas nas escolas do ciclo fundamental II e médio. MÉTODOS Estudo transversal, com amostra aleatória sistemática de 263 dirigentes escolares. Os dados foram coletados nos anos de 2012 e 2013 por meio de um programa de envio de formulários pela internet. Aplicou-se questionário fechado, de autopreenchimento on-line. A análise estatística incluiu testes Qui-quadrado e modelos de regressão logística. A variável desfecho foi a presença de programa de prevenção ao uso de drogas inserido no cotidiano e no programa pedagógico da escola. As variáveis explicativas foram divididas em: dados demográficos do dirigente; características da escola e do currículo; educação em saúde; e consumo de drogas na escola. RESULTADOS Constatou-se que 42,5% (IC95% 36,1–49,1) das escolas avaliadas possuíam programa de prevenção ao uso de drogas. Com o modelo de regressão logística múltipla, observou-se que, a cada ano de atuação do dirigente na educação, a chance de a escola ter um programa aumentava em aproximadamente 4,0%. O fato de experimentar técnicas de ensino inovadoras também aumentou em cerca de seis vezes a chance de a escola desenvolver um programa de prevenção ao uso de drogas. As dificuldades na implantação dos programas foram mais presentes nas redes estadual e municipal, quando comparadas à rede privada, destacando-se: a falta de material didático, a falta de dinheiro e as demandas concorrentes para ensino de outras disciplinas. CONCLUSÕES A implantação de programas de prevenção ao uso de drogas no município de São Paulo está associada à experiência do dirigente escolar na educação e nas estratégias de ensino da escola

A constructivist model of bank branch front-office employee evaluation: an FCM-SD-based approach

The banking sector is one of the primary drivers of economic development. This sector has been affected by various crises throughout its history – most recently, the 2008 financial and economic crisis. In response, banking institutions have had to make diverse changes to their procedures and deal with new concerns related to changes within markets. One of the main recent developments in this sector is the new commercial function assigned to bank branch front-office employees, who have become responsible for selling financial products and services, as well as recruiting and retaining clients. As a result, the sector needs new employee performance evaluation methods in line with banks and staff members’ requirements. This study combined fuzzy cognitive mapping techniques and the system dynamics (SD) approach to develop a well-informed performance analysis system for assessing bank branch front-office employees. The proposed system was validated by the Business Process Management Competence Center director at Millennium BCP – a Portuguese private banking corporation. The main difference between the model constructed in the present research and current evaluation practices is that the criteria were collected directly from multiple specialists working at different commercial banks, who deal daily with this decision problem. The model’s theoretical and practical implications are also discussed.info:eu-repo/semantics/publishedVersio

Factors associated with the implementation of programs for drug abuse prevention in schools

OBJECTIVE: To analyze if characteristics of managers, schools, and curriculum are associated with the implementation of programs for drug abuse prevention in elementary and high schools. METHODS: Cross-sectional study, with random sample of 263 school managers. Data were collected between 2012 and 2013 by a program that sends forms via internet. A closed self-filling questionnaire was applied online. Statistical analysis included Chi-square tests and logistic regression models. The outcome variable was the presence of program for drug abuse prevention inserted in the daily life and educational program of the school. The explanatory variables were divided into: demographic data of the manager characteristics of the school and of the curriculum health education and drug use in the school. RESULTS: We found that 42.5% (95% CI 36.1-49.1) of the evaluated schools had programs for drug abuse prevention. With the multiple logistic regression model, we observed that the more time the manager has worked with education, the chance of the school having a program increased at about 4.0%. Experimenting with innovative teaching techniques also increased at about six times the chance of the school developing a program for drug abuse prevention. The difficulties in the implementation of the programs were more present in state and municipal schools, when compared with private schools, due to, for instance: lack of teaching materials, lack of money, and competing demands for teaching other subjects. CONCLUSIONS: The implementation of programs for drug abuse prevention in the city of Sao Paulo is associated with the experience of the manager in education and with the teaching strategies of the school.OBJETIVO: Analisar se características dos dirigentes, das escolas e do currículo escolar estão associadas à implantação de programas de prevenção ao uso de drogas nas escolas do ciclo fundamental II e médio. MÉTODOS: Estudo transversal, com amostra aleatória sistemática de 263 dirigentes escolares. Os dados foram coletados nos anos de 2012 e 2013 por meio de um programa de envio de formulários pela internet. Aplicou-se questionário fechado, de autopreenchimento on-line. A análise estatística incluiu testes Qui-quadrado e modelos de regressão logística. A variável desfecho foi a presença de programa de prevenção ao uso de drogas inserido no cotidiano e no programa pedagógico da escola. As variáveis explicativas foram divididas em: dados demográficos do dirigente; características da escola e do currículo; educação em saúde; e consumo de drogas na escola. RESULTADOS: Constatou-se que 42,5% (IC95% 36,1–49,1) das escolas avaliadas possuíam programa de prevenção ao uso de drogas. Com o modelo de regressão logística múltipla, observou-se que, a cada ano de atuação do dirigente na educação, a chance de a escola ter um programa aumentava em aproximadamente 4,0%. O fato de experimentar técnicas de ensino inovadoras também aumentou em cerca de seis vezes a chance de a escola desenvolver um programa de prevenção ao uso de drogas. As dificuldades na implantação dos programas foram mais presentes nas redes estadual e municipal, quando comparadas à rede privada, destacando-se: a falta de material didático, a falta de dinheiro e as demandas concorrentes para ensino de outras disciplinas. CONCLUSÕES: A implantação de programas de prevenção ao uso de drogas no município de São Paulo está associada à experiência do dirigente escolar na educação e nas estratégias de ensino da escola.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES)Programa de Pós-Graduação em Saúde Coletiva. Universidade Federal de São Paulo. São Paulo, SP, BrasilSetor de Estatística Aplicada. Pró-reitoria de Pós-Graduação e Pesquisa. Universidade Federal de São Paulo. São Paulo, SP, BrasilDepartamento de Medicina Preventiva. Centro Brasileiro de Informações Sobre Drogas Psicotrópicas. Universidade Federal de São Paulo. São Paulo, SP, BrasilPrograma de Pós-Graduação em Saúde Coletiva. Universidade Federal de São Paulo. São Paulo, SP, BrasilSetor de Estatística Aplicada. Pró-reitoria de Pós-Graduação e Pesquisa. Universidade Federal de São Paulo. São Paulo, SP, BrasilDepartamento de Medicina Preventiva. Centro Brasileiro de Informações Sobre Drogas Psicotrópicas. Universidade Federal de São Paulo, Rua Botucatu 740,4 Andar, BR-04023900 Sao Paulo, SP, BrazilCNPq: 472991/2012-4Web of Scienc

The Role of Trust, Knowledge Diffusion and Contracts in Sunflower Production Chains in Brazil

The replacement of animal protein by plant protein is a trend in human nutrition and sunflower appears as a promising raw material. Dealing with innovation in the food industry requires attention not only to the product development process, but to the whole production chain related to it. Within this context and in face of the potential participation of Brazil in the business of sunflower protein food ingredients, this study aims to describe and analyze the operational dynamics of sunflower production chains in Brazil. To deal with this issue, we adopted the multiple-case study approach based on three production chains of sunflower oil in Brazil. Transaction cost economics and social network are the theoretical background for the analysis. Our findings suggest an environment with high transaction costs in the operation of the production chains of sunflower oil in Brazil. The processing company is the chain coordinator agent, being responsible to attract the farmers to the business of sunflower, using the strategies of crop promotion and verticalization. Crop promotion is in some degree the pattern of chain operation for all cases. It refers to a set of actions generally coordinated by the processing company aiming to encourage and assist farmers in the growing of sunflower. Moreover, it serves as a trust building and supervision strategy. Regional features influence the chain operation in terms of crop promotion applied by the processing company and the role of agents from farm supply retail stores (FSRS). The strategies of crop promotion and verticalization have not been sufficient to easily guarantee the provision of sunflower to the processing companies. Our findings show that if investments in the production of sunflower protein food ingredients are to be made in Brazil, it is necessary to consider the complex institutional arrangements in which the sunflower production chains operate, seeking to guarantee the necessary provision of raw material for the processing company

Using functional genetic screens to understand and overcome PARP inhibitor resistance

Heterozygous germ-line mutations in BRCA1 and BRCA2 predispose to several types of cancer. Owing to their roles in the error-free repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), lack of BRCA1/2 in these tumors results in DNA damage defects that can be specifically targeted by the inhibition of Poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is a key sensor of DNA damage and its inhibition has been shown to be synthetically lethal with deficiencies in HR, resulting in the selective killing of BRCA1/2-deficient tumor cells, while sparing BRCA1/2-proficient non-tumor cells. The success of this approach has resulted in the approval of four PARP1 inhibitors (PARPi) for the treatment of ovarian, breast, prostate and pancreatic cancers. However, drug resistance poses a major obstacle as, despite initial responses, patients receiving PARPi often develop resistance to the treatment. Understanding the molecular mechanisms behind PARPi resistance is therefore crucial to identify key determinants of PARPi response and to find combination treatment strategies to overcome resistance to PARPi by preventing, delaying or targeting resistant clones. In this thesis, we expanded our insights into the molecular mechanisms underlying PARPi resistance by conducting functional genetic screens in PARPi-resistance cell lines. Toxicolog