Philip Morris International R and D


Philip Morris International R and D


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Marx U.,TissUse GmbH | Andersson T.B.,Astrazeneca | Andersson T.B.,Karolinska Institutet | Bahinski A.,Wyss Institute for Biologically Inspired Engineering | And 34 more authors.
Altex | Year: 2016

The recent advent of microphysiological systems-microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro-promises to enable a global paradigm shift in drug development. An extraordinary US government initiative and various dedicated research programs in Europe and Asia recently have led to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis will model various disease stages and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus replacing the use of laboratory animal models. Here, thirty-six experts from academia, industry and regulatory bodies present the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies as well as various national and international programs are highlighted. Finally, a roadmap into the future towards more predictive and regulatory-accepted substance testing on a global scale is outlined.

Gregg E.,ENI S.p.A | Bachmann T.,Philip Morris International R and D | Bito R.,Japan Tobacco Inc. | Cahours X.,Imperial Tobacco Group | And 5 more authors.
Beitrage zur Tabakforschung International/ Contributions to Tobacco Research | Year: 2013

In recent years, the increased availability of tobacco products other than conventional cigarettes, the use of puffing topography devices for smoking behaviour studies and the use of biomarkers to study smoke constituents exposure have generated the need for a more comprehensive set of definitions concerning smoking behaviour and exposure to smoke. The definitions offered in this paper are based on many years of practical experience and on consensus within a broad group of scientists working in these areas. It is intended that, with wider and more consistent usage, these definitions should reduce any misunderstandings and facilitate interpretation of future studies.

Meskauskiene R.,NEBION AG | Laule O.,ETH Zurich | Laule O.,NEBION AG | Ivanov N.V.,Philip Morris International R and D | And 5 more authors.
Plant Methods | Year: 2013

Background: It is generally accepted that controlled vocabularies are necessary to systematically integrate data from various sources. During the last decade, several plant ontologies have been developed, some of which are community specific or were developed for a particular purpose. In most cases, the practical application of these ontologies has been limited to systematically storing experimental data. Due to technical constraints, complex data structures and term redundancies, it has been difficult to apply them directly into analysis tools.Results: Here, we describe a simplified and cross-species compatible set of controlled vocabularies for plant anatomy, focussing mainly on monocotypledonous and dicotyledonous crop and model plants. Their content was designed primarily for their direct use in graphical visualization tools. Specifically, we created annotation vocabularies that can be understood by non-specialists, are minimally redundant, simply structured, have low tree depth, and we tested them practically in the frame of Genevestigator.Conclusions: The application of the proposed ontologies enabled the aggregation of data from hundreds of experiments to visualize gene expression across tissue types. It also facilitated the comparison of expression across species. The described controlled vocabularies are maintained by a dedicated curation team and are available upon request. © 2013 Meskauskiene et al.; licensee BioMed Central Ltd.

Zimmermann P.,NEBION AG | Bleuler S.,NEBION AG | Laule O.,NEBION AG | Martin F.,Philip Morris International R and D | And 7 more authors.
BioData Mining | Year: 2014

Reference datasets are often used to compare, interpret or validate experimental data and analytical methods. In the field of gene expression, several reference datasets have been published. Typically, they consist of individual baseline or spike-in experiments carried out in a single laboratory and representing a particular set of conditions.Here, we describe a new type of standardized datasets representative for the spatial and temporal dimensions of gene expression. They result from integrating expression data from a large number of globally normalized and quality controlled public experiments. Expression data is aggregated by anatomical part or stage of development to yield a representative transcriptome for each category. For example, we created a genome-wide expression dataset representing the FDA tissue panel across 35 tissue types. The proposed datasets were created for human and several model organisms and are publicly available at. © 2014Zimmermann et al.; licensee BioMed Central Ltd.

Ivanov N.V.,Philip Morris International R and D | Poussin C.,Philip Morris International R and D | Boue S.,Philip Morris International R and D | Martin F.,Philip Morris International R and D | And 4 more authors.
BCB 2015 - 6th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics | Year: 2015

Risk assessment in the context of 21st century toxicology relies on the elucidation and understanding of mechanisms of toxicity. For that purpose, datasets generated by high-throughput technologies (e.g., high-throughput/content screening) combined with various omics data types are now generated in vitro to test large and diverse set of chemicals (e.g. ToxCast). The development of relevant computational approaches for the analysis and integration of these big data remains challenging and requires qualitative and quantitative evaluation. The current scope of sbv IMPROVER (Industrial Methodology for Process Verification in Research; is the verification of methods and concepts in systems biology research via challenges opened to the scientific community. Previous challenges brought new insights on methods and their associated results that address questions about diagnostic signatures, the translatability of biological responses/processes across species, and the relevance of biological causal network models. A new sbv IMPROVER challenge will be introduced aiming at evaluating (i) methodologies for the identification of specific biomarkers of exposure and (ii) the predictability by omics data of toxicity mechanisms when cells/tissues in vitro or whole organisms are exposed to individual chemical molecules or mixtures. Participants will be provided with high quality data sets to develop predictive models/classifiers. For this challenge, the integration of a priori biological knowledge in the development of computational approaches may be required to enable biological interpretability/understanding of the predictions. The results and post-challenge analyses will be shared with the scientific community, and will open new avenues in the field of systems toxicology. Copyright is held by the author/owner(s).

Aydin N.,Philip Morris International R and D | Chardonnens F.,Philip Morris International R and D | Rotach M.,Philip Morris International R and D
Beitrage zur Tabakforschung International/ Contributions to Tobacco Research | Year: 2012

Because many physicochemical properties of tobacco are highly sensitive to its moisture content, the determination of water level is an important parameter for tobacco characterization. A headspace volumetric Karl Fischer titration (HS-V-KFT) method is presented for the quantification of water content in different finished tobacco materials. The parameters affecting the extraction of water from the tobacco materials were the sample size and the oven temperature which have been optimized. The extraction of water from the samples was achieved within a reasonable time (<25 min) with a sample size of 200 mg and an optimum temperature of between 90 °C and 100 °C. The results of the water determination by HS-V-KFT at the optimized parameters were in good agreement with those obtained by standard volumetric Karl Fischer titration. HS-V-KFT showed very good repeatability (RSD r 0.9%) and intermediate precision (RSD iR 1.1%). With respect to a considerable time saving, solvent consumption reduction, precision and accuracy, HS-V-KFT can therefore be suggested as the method of choice to determine water amount in finished tobacco products.

Boue S.,Philip Morris International R and D | Tarasov K.,Zora Biosciences Oy | Janis M.,Zora Biosciences Oy | Lebrun S.,Philip Morris International R and D | And 9 more authors.
Atherosclerosis | Year: 2012

Objective: Although relationships between smoking and cardiovascular diseases (CVD), and between CVD and lipids are established, the direct impact of smoking on lipidomes is not well understood. We investigated the effect of mainstream cigarette smoke (CS) exposure on plasma, liver, and aorta molecular lipid profiles, and liver transcriptome in the ApoE-/- mouse, a well-established mouse model for human atherogenesis. Methods: Plasma, liver, and aorta samples from ApoE-/- mice exposed to CS or fresh air (sham) for six months were extracted for lipids using robotic-assisted method and analyzed by mass spectrometry. Gene expression in the liver was obtained on microarrays. Development of atherosclerosis in the aorta was further assessed by plaque size in the aortic arch and lipoprotein concentration in plasma and plaque. Results: CS increased most lipid classes and molecular lipid species. In plasma, free cholesterol, ceramides, cerebrosides, and most phospholipids were increased in CS-exposed mice. In the liver, several lipid species including free and esterified cholesterol, triacylglycerols, phospholipids, sphingomyelins, and ceramides were elevated. In the aorta, more than 2-fold higher cholesteryl ester (CE), lysophosphatidylcholine, and glucosyl/galactosylceramide levels were seen. Moreover, CS exposure induced a significant decrease in several plasma CE and phosphatidylcholine species that contained polyunsaturated fatty acids. Genes involved in amino acid and lipid metabolism showed perturbed transcription profiles in the liver. Conclusion: We have quantified some of the molecular changes that accompany the increase of plaque size that is accelerated by CS exposure in the aortae of ApoE-/- mice. These results suggest that specific changes in the lipidome and transcriptome, for example in ceramide and polyunsaturated fatty acid species, may be associated with atherosclerosis. © 2012 Elsevier Ireland Ltd.

Laino T.,IBM | Tuma C.,IBM | Moor P.,Philip Morris International R and D | Martin E.,Philip Morris International R and D | And 3 more authors.
Journal of Physical Chemistry A | Year: 2012

Propylene glycol and triacetin are chemical compounds, commonly used as food additives. Though the usage of the pure chemicals is not considered harmful when used as dietary supplements, little is known about the nature of their thermal degradation products and the impact they may have on human health. For these reasons, in this manuscript we investigate the thermal decomposition mechanisms of both neutral propylene glycol and triacetin in the gas phase by a novel simulation framework. This is based on a free energy sampling methodology followed by an accurate energy refinement. Structures, Gibbs free energy barriers, and rate constants at 800 K were computed for the different steps involved in the two pyrolytic processes. The thermal decomposition mechanisms found theoretically for propylene glycol and triacetin were validated by a qualitative experimental investigation using gas-phase chromatography-mass spectroscopy, with excellent agreement. The results provide a validation of the novel simulation framework and shed light on the potential hazard to the health that propylene glycol and triacetin may have when exposed to high temperatures. © 2012 American Chemical Society.

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