Gene Expression Analysis of the Hepatotoxicant Methapyrilene in Primary Rat Hepatocytes: An Interlaboratory Study

Genomics technologies are used in several disciplines, including toxicology. However, these technologies are relatively new, and their applications require further investigations. When investigators apply these technologies to in vitro experiments, two major issues need to be clarified: a) can in vitro toxicity studies, in combination with genomics analyses, be used to predict the toxicity of a compound; and b) are the generated toxicogenomics data reproducible between laboratories? These questions were addressed by an interlaboratory study with laboratories of four pharmaceutical companies. We evaluated gene expression patterns from cultured rat primary hepatocytes after a 24-hr incubation with methapyrilene (MP). Extensive data analysis showed that comparison of genomics data from different sources is complex because both experimental and statistical variability are important confounding factors. However, appropriate statistical tools allowed us to use gene expression profiles to distinguish high-dose–treated cells from vehicle-treated cells. Moreover, we correctly identified MP in an independently generated in vitro database, underlining that in vitro toxicogenomics could be a predictive tool for toxicity. From a mechanistic point of view, despite the observed site-to-site variability, there was good concordance regarding the affected biologic processes. Several subsets of regulated genes were obtained by analyzing the data sets with one method or using different statistical analysis methods. The identified genes are involved in cellular processes that are associated to the exposure of primary hepatocytes to MP. Whether they are specific for MP and are cause or consequence of the toxicity requires further investigations

Зміст та основні цілі стимулювання збуту на підприємстві

Стаття присвячена висвітленню сутності стимулювання підприємства, як важливої складової для забезпечення ефективного його функціонування, а також проаналізовано головні завдання, та основні переваги та недоліки заходів, які використовуються у системі стимулювання збуту. У статті розглянуто зміст стимулювання збуту продукції підприємства, його цілі та завдання. Виявлено, що стимулювання збуту ‒ це система короткострокових спонукальних заходів на тимчасовій або територіальній основі, що чинить вплив на трьох учасників ринку (споживачів, торгових посередників, торговий персонал), яка покликана стимулювати негайне здійснення покупки і прискорений збут продукції. Наведена характеристика сучасних засобів і прийомів стимулювання збуту. Розглянуто класифікацію стимулювання збуту продукції підприємства за виникненням і впливом на покупців. Дістали подальшого розвитку теоретичні положе ння стимулювання збуту, в тому числі визначення його основних напрямків.The article is devoted to highlighting the essence of stimulating the enterprise as an important component for ensuring its effective functioning, and also analyzed the main tasks and the main advantages and disadvantages of those used in the sales promotion system. The article deals with the content of sales’ promotion in the complex of product promotion, its goals and tasks. It is found that sales promotion is a system of short-term incentives on a temporary or territorial basis, affects three market part icipants (consumers, resellers, sales personnel), which is designed to stimulate immediate purchase and accelerated sales. The characteristic of modern means and methods of sales’ promotion is given. The classification of sales promotion in the work on occurrence and influence on buyers is described. The theoretical positions of sales’ promotion were furt her developed, the main directions of sales promotion were established

Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene.

Several studies using microarrays have shown that changes in gene expression provide information about the mechanism of toxicity induced by xenobiotic agents. Nevertheless, the issue of whether gene expression profiles are reproducible across different laboratories remains to be determined. To address this question, several members of the Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute evaluated the liver gene expression profiles of rats treated with methapyrilene (MP). Animals were treated at one facility, and RNA was distributed to five different sites for gene expression analysis. A preliminary evaluation of the number of modulated genes uncovered striking differences between the five different sites. However, additional data analysis demonstrated that these differences had an effect on the absolute gene expression results but not on the outcome of the study. For all users, unsupervised algorithms showed that gene expression allows the distinction of the high dose of MP from controls and low dose. In addition, the use of a supervised analysis method (support vector machines) made it possible to correctly classify samples. In conclusion, the results show that, despite some variability, robust gene expression changes were consistent between sites. In addition, key expression changes related to the mechanism of MP-induced hepatotoxicity were identified. These results provide critical information regarding the consistency of microarray results across different laboratories and shed light on the strengths and limitations of expression profiling in drug safety analysis

Performance Verification of the FlashCam Prototype Camera for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is a future gamma-ray observatory that is planned to significantly improve upon the sensitivity and precision of the current generation of Cherenkov telescopes. The observatory will consist of several dozens of telescopes with different sizes and equipped with different types of cameras. Of these, the FlashCam camera system is the first to implement a fully digital signal processing chain which allows for a traceable, configurable trigger scheme and flexible signal reconstruction. As of autumn 2016, a prototype FlashCam camera for the medium-sized telescopes of CTA nears completion. First results of the ongoing system tests demonstrate that the signal chain and the readout system surpass CTA requirements. The stability of the system is shown using long-term temperature cycling.Comment: 5 pages, 13 figures, Proceedings of the 9th International Workshop on Ring Imaging Cherenkov Detectors (RICH 2016), Lake Bled, Sloveni

FlashCam: a fully-digital camera for the medium-sized telescopes of the Cherenkov Telescope Array

The FlashCam group is currently preparing photomultiplier-tube based cameras proposed for the medium-sized telescopes (MST) of the Cherenkov Telescope Array (CTA). The cameras are designed around the FlashCam readout concept which is the first fully-digital readout system for Cherenkov cameras, based on commercial FADCs and FPGAs as key components for the front-end electronics modules and a high performance camera server as back-end. This contribution describes the progress of the full-scale FlashCam camera prototype currently under construction, as well as performance results also obtained with earlier demonstrator setups. Plans towards the production and implementation of FlashCams on site are also briefly presented.Comment: 8 pages, 6 figures. In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

On the Economics of Decarbonization in an Imperfect World

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