@article{ValeroBung2016, author = {Valero, Daniel and Bung, Daniel Bernhard}, title = {Development of the interfacial air layer in the non-aerated region of high-velocity spillway flows: Instabilities growth, entrapped air and influence on the self-aeration onset}, series = {International Journal of Multiphase Flow}, volume = {84}, journal = {International Journal of Multiphase Flow}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0301-9322}, doi = {10.1016/j.ijmultiphaseflow.2016.04.012}, pages = {66 -- 74}, year = {2016}, abstract = {Self-aeration is traditionally explained by the water turbulent boundary layer outer edge intersection with the free surface. This paper presents a discussion on the commonly accepted hypothesis behind the computation of the critical point of self-aeration in spillway flows and a new formulation is proposed based on the existence of a developing air flow over the free surface. Upstream of the inception point of self-aeration, some surface roughening has been often reported in previous studies which consequently implies some entrapped air transport and air-water flows coupling. Such air flow is proven in this study by presenting measured air velocities and computing the air boundary layer thickness for a 1V:2H smooth chute flow. Additionally, the growth rate of free surface waves has been analysed by means of Ultrasonic Sensors measurements, obtaining also the entrapped air concentration. High-speed camera imaging has been used for qualitative study of the flow perturbations.}, language = {en} } @article{GhoschBaierSchuetzetal.2016, author = {Ghosch, S. and Baier, M. and Sch{\"u}tz, J. and Schneider, Felix and Scherer, Ulrich W.}, title = {Analysis of electronic autoradiographs by mathematical post-processing}, series = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, volume = {171}, journal = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, number = {1-2}, publisher = {Taylor \& Francis}, address = {London}, issn = {1029-4953}, doi = {10.1080/10420150.2016.1155587}, pages = {161 -- 172}, year = {2016}, abstract = {Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution.}, language = {en} } @article{KolditzAlbinAbeletal.2016, author = {Kolditz, Melanie and Albin, Thivaharan and Abel, Dirk and Fasse, Alessandro and Br{\"u}ggemann, Gert-Peter and Albracht, Kirsten}, title = {Evaluation of foot position and orientation as manipulated variables to control external knee adduction moments in leg extension training}, series = {Computer methods and programs in biomedicine}, volume = {171}, journal = {Computer methods and programs in biomedicine}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0169-2607}, doi = {10.1016/j.cmpb.2016.09.005}, pages = {81 -- 86}, year = {2016}, abstract = {Background and Objective Effective leg extension training at a leg press requires high forces, which need to be controlled to avoid training-induced damage. In order to avoid high external knee adduction moments, which are one reason for unphysiological loadings on knee joint structures, both training movements and the whole reaction force vector need to be observed. In this study, the applicability of lateral and medial changes in foot orientation and position as possible manipulated variables to control external knee adduction moments is investigated. As secondary parameters both the medio-lateral position of the center of pressure and the frontal-plane orientation of the reaction force vector are analyzed. Methods Knee adduction moments are estimated using a dynamic model of the musculoskeletal system together with the measured reaction force vector and the motion of the subject by solving the inverse kinematic and dynamic problem. Six different foot conditions with varying positions and orientations of the foot in a static leg press are evaluated and compared to a neutral foot position. Results Both lateral and medial wedges under the foot and medial and lateral shifts of the foot can influence external knee adduction moments in the presented study with six healthy subjects. Different effects are observed with the varying conditions: the pose of the leg is changed and the direction and center of pressure of the reaction force vector is influenced. Each effect results in a different direction or center of pressure of the reaction force vector. Conclusions The results allow the conclusion that foot position and orientation can be used as manipulated variables in a control loop to actively control knee adduction moments in leg extension training.}, language = {en} } @article{BelavyAlbrachtBruggemannetal.2016, author = {Belavy, Daniel L. and Albracht, Kirsten and Bruggemann, Gert-Peter and Vergroesen, Pieter-Paul A. and Dieen, Jaap H. van}, title = {Can exercise positively influence the intervertebral disc?}, series = {Sports Medicine}, volume = {46}, journal = {Sports Medicine}, number = {4}, publisher = {Springer}, address = {Berlin}, issn = {1179-2035}, doi = {10.1007/s40279-015-0444-2}, pages = {473 -- 485}, year = {2016}, abstract = {To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a 'critical period' for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.}, language = {en} } @article{FerreinSchifferBooysenetal.2016, author = {Ferrein, Alexander and Schiffer, Stefan and Booysen, T. and Stopforth, R.}, title = {Why it is harder to run RoboCup in South Africa: Experiences from German South African collaborations}, series = {International Journal of Advanced Robotic Systems}, volume = {13}, journal = {International Journal of Advanced Robotic Systems}, number = {5}, issn = {1729-8806}, doi = {10.1177/1729881416662789}, pages = {1 -- 13}, year = {2016}, abstract = {Robots are widely used as a vehicle to spark interest in science and technology in learners. A number of initiatives focus on this issue, for instance, the Roberta Initiative, the FIRST Lego League, the World Robot Olympiad and RoboCup Junior. Robotic competitions are valuable not only for school learners but also for university students, as the RoboCup initiative shows. Besides technical skills, the students get some project exposure and experience what it means to finish their tasks on time. But qualifying students for future high-tech areas should not only be for students from developed countries. In this article, we present our experiences with research and education in robotics within the RoboCup initiative, in Germany and South Africa; we report on our experiences with trying to get the RoboCup initiative in South Africa going. RoboCup has a huge support base of academic institutions in Germany; this is not the case in South Africa. We present our 'north-south' collaboration initiatives in RoboCup between Germany and South Africa and discuss some of the reasons why we think it is harder to run RoboCup in South Africa.}, language = {en} } @article{MiyamotoSatoAbeetal.2016, author = {Miyamoto, Ko-Ichiro and Sato, Takuya and Abe, Minami and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Yoshinobu, Tatsuo}, title = {Light-addressable potentiometric sensor as a sensing element in plug-based microfluidic devices}, series = {Micromachines}, volume = {7}, journal = {Micromachines}, number = {7}, publisher = {MDPI}, address = {Basel}, issn = {2072-666X}, doi = {10.3390/mi7070111}, pages = {111}, year = {2016}, abstract = {A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement.}, 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} } @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{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{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} }