Family rivalry in the testis: Retinoblastoma protein and E2F transcription factors in testicular development and adult spermatogenesis

Disorders of male reproductive health are becoming increasingly prevalent globally. These defects, ranging from decreasing sperm counts to an increasing rate of infertility and testicular cancer, have a common origin in the early phases of testicular development, but the exact mechanisms that cause them remain unknown. Testicular development and adult spermatogenesis are complex processes in which different cell types undergo mitosis, meiosis, differentiation and apoptosis. The retinoblastoma protein family and its associated E2F transcription factors are key regulators of these cellular events. In the present study, the functions of these factors in postnatal testicular development and adult spermatogenesis were explored using different animal models. In addition, a new application of flow cytometry to study testicular cell dynamics was developed. An ablation of retinoblastoma protein in mouse Sertoli cells resulted in their cell cycle re-entry in adult testes, dedifferentiation and a severe spermatogenic defect. We showed that deregulated E2F3 contributed to these changes. Our results indicated that the E2F1 transcription factor is critical for the control of apoptosis in the developing postnatal testis. In the adult testis, E2F1 controls the maintenance of the spermatogonial stem cell pool, in addition to inhibiting apoptosis of spermatocytes. In summary, this study elucidated the complex interdependencies of the RB and E2F transcription factor families in the control of postnatal testicular development and adult spermatogenesis. Furthermore, this study provided a new methodology for the analysis of testicular cells.

Development of Project Logistics in Engineering, Procurement and Construction Projects

The aim of this Master’s Thesis is to develop project logistics functions in large scale en-gineering, procurement and construction projects. The background of the research topic is compounded from two separate subjects; OPAL Program and case study of an actual EPC project. The purpose is to examine Project Logistics process in accordance with OPAL Program as well as logistics process in focus EPC project. Both entities are researched by using the case study research methodology. Logistics process of the focus EPC project is described as well as presented and in addi-tion, logistics related findings and observations are introduced. Significant findings and observations are found from logistics costs as well as shipment volume estimations in the early phase of the focus ECP project. A notable finding is also that because goods were transported as readily assembled as possible it caused expensive oversized cargo deliveries. From findings and observation of the focus EPC project it can be derived that logistics has to be involved in the early sales phase in order to receive more accurate logistics cost esti-mations for project deliveries. It is also noticed that in order to obtain savings in logistics costs, oversized deliveries must be avoided.