@article{AimenovaDigelEshibaev2016, author = {Aimenova, Zh. E. and Digel, Ilya and Eshibaev, А. А.}, title = {Dynamics of accumulation of lagochirzin in Lagochilus setulosus phytomass during the growing season and also features of its cultivation in the conditions of a typical sierozem}, series = {KazNU Bulletin. Biology series}, volume = {69}, journal = {KazNU Bulletin. Biology series}, number = {4}, publisher = {Al-Farabi Kazakh National University}, address = {Almaty}, issn = {1563-0218}, pages = {4 -- 11}, year = {2016}, abstract = {L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen - lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 \% higher than in the wild-growing species.}, language = {en} } @article{TuraliyevaYeshibaevSaparbekovaetal.2016, author = {Turaliyeva, M. and Yeshibaev, A. and Saparbekova, A. and Akynova, L. and Abildayeva, R. and Sadenova, M. and Sartayeva, K. and Schieffer, Andre and Digel, Ilya}, title = {Species composition and injuriousness of stranger xylophilous fauna affecting indigenous urban dendroflora of Central Asia}, series = {Asian journal of microbiology, biotechnology \& environmental sciences : AJMBES}, volume = {18}, journal = {Asian journal of microbiology, biotechnology \& environmental sciences : AJMBES}, number = {2}, publisher = {EM International}, issn = {0972-3005}, pages = {359 -- 366}, year = {2016}, abstract = {At the present time, one of the most serious environmental problems of Central Asia and South Kazakhstan is the ongoing large-scale deterioration of principal urban tree populations. Several major centers of massive spread of invasive plant pests have been found in urban dendroflora of this region. The degree of damage of seven most wide-spread aboriginal tree species was found to range from 21.4±1.1 to 85.4±1.8\%. In particular, the integrity of the native communities of sycamore (Platanus spp.), willow (Salix spp.), poplar (Populus spp.) and elm (Ulmus spp.) is highly endangered. Our taxonomic analysis of the most dangerous tree pests of the region has revealed them as neobiontic xylophilous insects such as Cossus cossus L. (Order: Lepidoptera L.) Monochamus urussovi Fisch., Monochamus sutor L., Acanthocinus aedelis L. and {\~N}etonia aureate L. (Order: Coleoptera L.). We relate the origin of this threatening trend with the import of industrial wood in the mid 90’s of the last century that was associated with high degree of the constructional work in the region. Because of the absence of efficient natural predators of the pest species, the application of microbiological methods of the pest control and limitation is suggested.}, language = {en} } @inproceedings{Matcha2016, author = {Matcha, Heike}, title = {From Designing Buildings from Systems to Designing Systems for Buildings}, series = {Complexity \& Simplicity - Proceedings of the 34th eCAADe Conference - Volume 1}, booktitle = {Complexity \& Simplicity - Proceedings of the 34th eCAADe Conference - Volume 1}, editor = {Herneoja, Aulikki and {\"O}sterlund, Toni and Markkanen, Piia}, publisher = {ECAADe}, address = {Oulu, Finland}, doi = {10.52842/conf.ecaade.2016.1.237}, pages = {237 -- 240}, year = {2016}, abstract = {We study the novel possibilities computer aided design and production open up for the design of building systems. Such systems today can, via individualized mass production, consist of a larger number and more complex parts than previously and therefore be assembled into more complex wholes. This opens up the possibility of designing specialized systems specifically for single buildings. The common order of starting with a building system and designing a building using this system can be reversed to designing a building first and then developing a system specifically for that building. We present and discuss research that incorporates students design projects into research work and fosters links between research and teaching.}, language = {en} } @phdthesis{Frotscher2016, author = {Frotscher, Ralf}, title = {Electromechanical modeling and simulation of thin cardiac tissue constructs - smoothed FEM applied to a biomechanical plate problem}, year = {2016}, language = {en} } @inproceedings{HoevelerJanser2016, author = {Hoeveler, Bastian and Janser, Frank}, title = {The aerodynamically optimized design of a fan-in-wing duct}, series = {Applied Aerodynamics Research Conference 2016, Bristol, GB, Jul 19-21, 2016}, booktitle = {Applied Aerodynamics Research Conference 2016, Bristol, GB, Jul 19-21, 2016}, isbn = {1-85768-371-4}, pages = {1 -- 10}, year = {2016}, language = {en} } @inproceedings{RieperGebhardtStucker2016, author = {Rieper, Harald and Gebhardt, Andreas and Stucker, Brent}, title = {Process parameters for Selective Laser Melting of AgCu7}, series = {DDMC, Fraunhofer Direct Digital Manufacturing Conference, 3}, booktitle = {DDMC, Fraunhofer Direct Digital Manufacturing Conference, 3}, publisher = {Fraunhofer-Verlag}, address = {Stuttgart}, isbn = {978-3-8396-1001-5}, pages = {171 -- 176}, year = {2016}, language = {en} } @incollection{ScheerChuSalphatietal.2016, author = {Scheer, Nico and Chu, Xiaoyan and Salphati, Laurent and Zamek-Gliszczynski, Maciej J.}, title = {Knockout and humanized animal models to study membrane transporters in drug development}, series = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development}, booktitle = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development}, editor = {Nicholls, Glynis}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, isbn = {978-1-78262-379-3}, doi = {10.1039/9781782623793-00298}, pages = {298 -- 332}, year = {2016}, language = {en} } @article{ScheerWilson2016, author = {Scheer, Nico and Wilson, Ian D.}, title = {A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity}, series = {Drug Discovery Today}, volume = {21}, journal = {Drug Discovery Today}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2015.09.002}, pages = {250 -- 263}, year = {2016}, abstract = {Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug-drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.}, language = {en} } @article{DallasSalphatiGomezZepedaetal.2016, author = {Dallas, Shannon and Salphati, Laurent and Gomez-Zepeda, David and Wanek, Thomas and Chen, Liangfu and Chu, Xiaoyan and Kunta, Jeevan and Mezler, Mario and Menet, Marie-Claude and Chasseigneaux, Stephanie and Decl{\`e}ves, Xavier and Langer, Oliver and Pierre, Esaie and DiLoreto, Karen and Hoft, Carolin and Laplanche, Loic and Pang, Jodie and Pereira, Tony and Andonian, Clara and Simic, Damir and Rode, Anja and Yabut, Jocelyn and Zhang, Xiaolin and Scheer, Nico}, title = {Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model}, series = {Molecular Pharmacology}, volume = {89}, journal = {Molecular Pharmacology}, number = {5}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.115.102079}, pages = {492 -- 504}, year = {2016}, abstract = {Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp-/-) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.}, language = {en} } @article{ZhangHeimbachScheeretal.2016, author = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan}, title = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling}, series = {Journal of Pharmaceutical Sciences}, volume = {Volume 105}, journal = {Journal of Pharmaceutical Sciences}, number = {Issue 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-3549}, doi = {doi.org/10.1016/j.xphs.2016.01.021}, pages = {1398 -- 1404}, year = {2016}, abstract = {NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.}, language = {en} }