Investigating the Origins of Cancer in the Intestinal Crypt with a Gene Network Agent Based Hybrid Model

Colorectal cancer (CRC) is the second most common tumour in the world (Bray, 2018). It has been proposed that morbidity and mortality could be mitigated by screening methods that identify key genetic mutations in the DNA of a patient’s biosample (Traverso, 2002). However, for this to work, a theoretical understanding of the most likely mutations that initiate malignant transformation, and how they affect subsequent microevolution, is needed. Specifically, we hypothesise that there is a CRC-proliferative mutation that is more likely to be initially fixated in the crypt. To investigate this, we developed an agent-based model of cells in the colon crypt that shows emergent biological homeostasis at the tissue level from the cellular and molecular interactions. We equipped each of the cells with a molecular gene network which, in their wildtype state, regulates homeostasis in the crypt and recapitulates known behaviour. We identified and modelled key genes implicated in CRC which, when mutated, alter the rate of death and division of cells. We used this model to study the biological first principles of the fixation of mutations, offering key spatial and temporal understanding of this process. We discuss the impact and clinical relevance of proliferative genetic mutations in isolation, pointing to the KRAS gene as a likely mutation to be initially fixed in the crypt

Перспективы развития биотехнологий

В статье затронуты проблемы демографического кризиса. Рассмотрены вопросы развития биотехнологий, а так же существующие виды биотехнологий. Более глубоко рассмотрен такой вид биотехнологии как биомедицина, представлены существующие наработки ученых в этой сфере. При изучении был сделан вывод, что развитие биотехнологии, в честности биомедицины приведет к повышению продолжительности жизни, а вследствие решения демографической проблемы.The article touches upon the problems of the demographic crisis. The questions of development of biotechnologies, as well as existing types of biotechnologies are considered. Deeply considered this kind of biotechnology as biomedicine, presents the existing developments of scientists in this field. The study concluded that the development of biotechnology, in the honesty of biomedicine, will lead to an increase in life expectancy, and as a result of solving the demographic problem

Исследование влияния изменения конструкций топочной камеры ТЭС БКЗ -420 на распределения продуктов горения

Объектом исследования является топочная камера котла БКЗ-420 АТЭЦ-2. Цель работы – 3D моделирование процессов тепломасса переноса, исследование влияния изменения конструкций топочной камеры на распределения продуктов горения. В процессе исследования проводились вычислительные эксперименты по исследованию аэродинамических, тепловых и концентрационных характеристик топочной камеры, поля скоростей, температуры, турбулентных характеристик, концентраций всех вредных пылегазовых выбросов и энергии. В результате исследования разработана оптимальная технология сжигания энергетического высокозольного топлива и наилучшие конструкционные параметры топочной камеры.The object of research is the combustion chamber of the boiler BKZ-420 TPP-2. Objective - 3D modeling transfer processes, the study of influence of structural changes of the combustion chamber to the distribution of the products of combustion. The study carried out computational experiments on the aerodynamic, thermal and concentration characteristics of the combustion chamber, the velocity field, temperature, turbulent characteristics, concentrations of harmful dust and gas emissions and energy. The study developed the optimum combustion technology of high-energy fuel and best structural parameters of the combustion chamber

Application of conflictology methods for evaluating physical protection systems effectiveness

At present, physical protection of nuclear material and nuclear facilities is actual. For the implementation of physical protection, Physical Protection System (PPS) is created at nuclear facilities. We all know that the most important characteristic is effectiveness of physical protection systems. PPS effectiveness value is determined by the probability that reaction forces can stop and intercept the intruder. There are many methods to assess the effectiveness of PPS. However, not all methods can provide an accurate quantitative assessment of the effectiveness of security systems. This work presents an approach for assessing the resistance of PPS to emerging threat (that is, the intruder to act against items of physical protection).Based on the fact that different processes are subject to universal physical laws and principles of development, a parallel between the concepts of Conflictology field was established to describe the interaction in the system "intruder against PPS"

Epac inhibits migration and proliferation of human prostate carcinoma cells

BACKGROUND: It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells. METHODS: The effect of Epac activation was determined by [(3)H] thymidine incorporation and scratch assays in PC-3 and DU 145 cells. Furthermore, cytoskeletal integrity was analysed by phalloidin staining. The participation of intracellular Epac effectors such as mitogen-activated protein (MAP) kinases, Rap1- and Rho-GTPases was determined by immunoblotting and pull-down assay. RESULTS: The specific Epac activator 8-pCPT-2'-O-Me-cAMP (8-pCPT) interfered with cytoskeletal integrity, reduced DNA synthesis, and migration. Although 8-pCPT activated Rap1, it inhibited MAP kinase signalling and RhoA activation. These findings were translated into functional effects such as inhibition of mitogenesis, cytoskeletal integrity, and migration. CONCLUSION: In human prostate carcinoma cells, Epac inhibits proliferative and migratory responses likely because of inhibition of MAP kinase and RhoA signalling pathways. Therefore, Epac might represent an attractive therapeutic target in the treatment of prostate cancer. British Journal of Cancer (2009) 101, 2038-2042. doi: 10.1038/sj.bjc.6605439 www.bjcancer.com Published online 17 November 2009 (C) 2009 Cancer Research U