A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention

Application of combinatorial testing techniques in complex event processing engines

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Testing practice has a critical place during the design, implementation and integration of software, hardware and complex systems composed of these. Cost of failures caused by bugs that could not be detected and fixed early in the process increase in a multiplicative way and adversely affect the overall projects costs. However, trying to do comprehensive tests generating correct outputs is also costly both time-wise and money-wise. Combinatorial Testing Techniques (CTT) have been a preferred method in software testing due to their quantifiable case coverage guarantees and appropriateness for automation. We observed that, Complex Event Processing (CEP) engines - commonly used today for real-time analysis over critical, high-volume signal processing applications (e.g. mobile communication, sensors, radar) - are NOT being systematically tested with approaches such as CTT. In this paper, we uniquely show applicability of CTT to CEP for fast creation of continuous query test suites and obtain promising results.TÜBİTAK ; European Commissio

The Energy-Navigator -A Web Based Platform for Quality Management in Buildings

Energy efficient buildings require high quality standards for all their technical equipment to enable their efficient and successful operation and management. Building simulations enable engineers to design integrated HVAC systems with complex building automation systems to control all their technical functions. Numerous studies show that especially these supposedly innovative buildings often do not reach their energy efficiency targets when in operation. Key reasons for the suboptimal performance are imprecise functional descriptions and a lack of commissioning and monitoring of the technical systems that leave suboptimal operation undetected. In the research project 'Energy Navigator' we create a web-based platform that enables engineers to create a comprehensive and precise functional description for the buildings services. The system reuses this functional description - written in an appropriate domain specific language - to control the building operation, to signal malfunctions or faults, and in particular to measure energy efficiency over time. The innovative approach of the platform is the combination of design and control within one artifact linking the phases of design and operation and improving the cost effectiveness for both services. The paper will describe the concept of the platform, the technical innovation and first application examples of the research project