Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis

Members of the transforming growth factor β (TGF-β) family have been genetically linked to vascular formation during embryogenesis. However, contradictory studies about the role of TGF-β and other family members with reported vascular functions, such as bone morphogenetic protein (BMP) 9, in physiological and pathological angiogenesis make the need for mechanistic studies apparent. We demonstrate, by genetic and pharmacological means, that the TGF-β and BMP9 receptor activin receptor-like kinase (ALK) 1 represents a new therapeutic target for tumor angiogenesis. Diminution of ALK1 gene dosage or systemic treatment with the ALK1-Fc fusion protein RAP-041 retarded tumor growth and progression by inhibition of angiogenesis in a transgenic mouse model of multistep tumorigenesis. Furthermore, RAP-041 significantly impaired the in vitro and in vivo angiogenic response toward vascular endothelial growth factor A and basic fibroblast growth factor. In seeking the mechanism for the observed effects, we uncovered an unexpected signaling synergy between TGF-β and BMP9, through which the combined action of the two factors augmented the endothelial cell response to angiogenic stimuli. We delineate a decisive role for signaling by TGF-β family members in tumor angiogenesis and offer mechanistic insight for the forthcoming clinical development of drugs blocking ALK1 in oncology

Teachers' use of mathematics textbooks in their teaching of mathematics

A research report submitted to the School of Education in partial fulfilment of the requirements for the degree of Master of Education. University of the Witwatersrand Johannesburg, 2017.This is a baseline descriptive case study on the use of mathematics textbooks by Grade 9 teachers in the Johannesburg East district. Three research methods were used to collect data, namely, a survey, direct observation and interviews. Responses from the survey and transcripts of lesson observations and those of interviews were analysed to establish how individual teachers use textbooks to mediate mathematics concepts to their learners and to find out whether teachers adhere to Curriculum and Assessment Policy Statement (CAPS) requirements with regard to the use of the four Mathematics CAPS cognitive levels. Findings from the study highlighted different approaches in teachers’ use of textbooks. Some of the aspects in Nicol and Crespo’s (2009) argument relating to different ways in which teachers use textbooks are perceptible in the findings. Contrary to Nicol and Crespo’s (2009) findings the study revealed that experience and level of qualification do not play a significant role in the use of textbook by individual teachers. The study also revealed that when selecting examples to demonstrate concepts, for learners’ classroom practice and for homework, teachers do not consciously select questions according to the four Mathematics CAPS cognitive levels but use questions as presented in various textbooks without necessarily rating them accordingly. The study reveals through a sample used that the majority of teachers would rather use prescribed textbooks than any other resource when preparing lessons, when teaching lessons, for learners’ classroom practice exercises, for homework and assessment.LG201

Designing a demand-driven supply chain dashboard

M.Com.The aim of this study was to design a demand-driven supply chain dashboard geared towards improving performance measurement in a medical technology company. In this case study, Becton Dickinson (BD) was used as an example of a medical technology company. Document analysis of BD supply chain documents was performed. Underpinning the qualitative content analysis construct was the SCOR® model supply chain performance attribute and a dashboard design framework. The combined strength of all the BD respondents’ documents reviewed in this study was used to map design elements for constructing a demand-driven supply chain dashboar

Gender, identity and institutional culture : women students' constructions of success at three South African universities

The Carnegie-South Africa Undergraduate Women's Scholarship Programme was set up in 2002 as a national scholarship programme targeted at young women wishing to study primarily in the fields of science and engineering at the undergraduate level. The study provides case studies of the diverse experiences of a selection of these young women at 3 universities: University of Cape Town, Kwa-Zulu-Natal and Pretoria. The chapters reflect on the university institutional cultures from the perspective of these young women and, through analysis of context, voice and discourse, attempt to cast light on their experiences and constructions of academic and social integration and success

Expression of human bone morphogenetic protein (BMP-2 and BMP-4) genes in transgenic bovine fibroblasts Expressão dos genes bone morphogenetic protein (BMP-2 e BMP-4) em fibroblastos bovinos transgênicos

<abstract language="por">cDNAs dos genes bone morphogenetic protein-2 (BMP-2) e bone morphogenetic protein-4 (BMP-4) foram sintetizados a partir de RNA total extraído de tecidos ósseos de pacientes que apresentavam trauma facial (fraturas do maxilar entre o 7º e o 10º dia pós-trauma) e clonados num vetor para expressão em células mamíferas, sob controle do promotor de citomegalovírus (CMV). Os vetores contendo os genes BMP-2 e o BMP-4 foram utilizados para a transfecção de fibroblastos bovinos. mRNAs foram indiretamente detectados por RT-PCR nas células transfectadas. As proteínas BMP-2 e BMP-4 foram detectadas mediante análises de Western blot. Os resultados demonstram a possibilidade de produção desses fatores de crescimento celular em fibroblastos bovinos. Essas células poderão ser utilizadas como fontes doadoras de material genético para a técnica de transferência nuclear na geração de animais transgênicos