@article{PennerUsherovichNiedermeieretal.2022,
  author    = {Penner, Crystal and Usherovich, Samuel and Niedermeier, Jana and B{\´e}langer-Champagne, Camille and Trinczek, Michael and Paulßen, Elisabeth and Hoehr, Cornelia},
  title     = {Organic Scintillator-Fibre Sensors for Proton Therapy Dosimetry: SCSF-3HF and EJ-260},
  series = {electronics},
  volume    = {12},
  journal   = {electronics},
  number    = {1},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2079-9292},
  doi       = {10.3390/electronics12010011},
  pages     = {12 Seiten},
  year      = {2022},
  abstract  = {In proton therapy, the dose from secondary neutrons to the patient can contribute to side effects and the creation of secondary cancer. A simple and fast detection system to distinguish between dose from protons and neutrons both in pretreatment verification as well as potentially in vivo monitoring is needed to minimize dose from secondary neutrons. Two 3 mm long, 1 mm diameter organic scintillators were tested for candidacy to be used in a proton-neutron discrimination detector. The SCSF-3HF (1500) scintillating fibre (Kuraray Co. Chiyoda-ku, Tokyo, Japan) and EJ-260 plastic scintillator (Eljen Technology, Sweetwater, TX, USA) were irradiated at the TRIUMF Neutron Facility and the Proton Therapy Research Centre. In the proton beam, we compared the raw Bragg peak and spread-out Bragg peak response to the industry standard Markus chamber detector. Both scintillator sensors exhibited quenching at high LET in the Bragg peak, presenting a peak-to-entrance ratio of 2.59 for the EJ-260 and 2.63 for the SCSF-3HF fibre, compared to 3.70 for the Markus chamber. The SCSF-3HF sensor demonstrated 1.3 times the sensitivity to protons and 3 times the sensitivity to neutrons as compared to the EJ-260 sensor. Combined with our equations relating neutron and proton contributions to dose during proton irradiations, and the application of Birks' quenching correction, these fibres provide valid candidates for inexpensive and replicable proton-neutron discrimination detectors},
  language  = {en}
}
@article{MatoniBerndt1980,
  author    = {Matoni, Georg and Berndt, Heinz},
  title     = {Thermal synthesis of the optical pure pentapeptide derivative Z-(L)-Ala-(L)-Phe-Gly-(L)-Phe-Gly-OMe},
  series = {Tetrahedron letters},
  volume    = {21},
  journal   = {Tetrahedron letters},
  number    = {1},
  issn      = {0040-4039},
  doi       = {10.1016/S0040-4039(00)93618-9},
  pages     = {37 -- 40},
  year      = {1980},
  language  = {en}
}
@article{EilmannZweifelBuchmannetal.2009,
  author    = {Eilmann, Britta and Zweifel, Roman and Buchmann, Nina and Fonti, Patrick and Rigling, Andreas},
  title     = {Drought-induced adaptation of the xylem in Scots pine and pubescent oak},
  series = {Tree Physiology},
  volume    = {29},
  journal   = {Tree Physiology},
  number    = {8},
  publisher = {Heron},
  address   = {Victoria, BC},
  issn      = {0829-318X (Print)},
  doi       = {10.1093/treephys/tpp035},
  pages     = {1011 -- 1020},
  year      = {2009},
  language  = {en}
}
@article{ElBerguiAbouabdillahBouriougetal.2023,
  author    = {El Bergui, Omnia and Abouabdillah, Aziz and Bourioug, Mohamed and Schmitz, Dominik and Biel, Markus and Aboudrare, Abdellah and Krauss, Manuel and Jomaa, Ahlem and Romuli, Sebastian and M{\"u}ller, Joachim and Fagroud, Mustapha and Bouabid, Rachid},
  title     = {Innovative solutions for drought: Evaluating hydrogel application on onion cultivation (Allium cepa) in Morocco},
  series = {Water},
  volume    = {15},
  journal   = {Water},
  number    = {11},
  publisher = {MDPI},
  address   = {Basel},
  doi       = {10.3390/w15111972},
  pages     = {Artikel 1972},
  year      = {2023},
  abstract  = {Throughout the last decade, and particularly in 2022, water scarcity has become a critical concern in Morocco and other Mediterranean countries. The lack of rainfall during spring was worsened by a succession of heat waves during the summer. To address this drought, innovative solutions, including the use of new technologies such as hydrogels, will be essential to transform agriculture. This paper presents the findings of a study that evaluated the impact of hydrogel application on onion (Allium cepa) cultivation in Meknes, Morocco. The treatments investigated in this study comprised two different types of hydrogel-based soil additives (Arbovit® polyacrylate and Huminsorb® polyacrylate), applied at two rates (30 and 20 kg/ha), and irrigated at two levels of water supply (100\% and 50\% of daily crop evapotranspiration; ETc). Two control treatments were included, without hydrogel application and with both water amounts. The experiment was conducted in an open field using a completely randomized design. The results indicated a significant impact of both hydrogel-type dose and water dose on onion plant growth, as evidenced by various vegetation parameters. Among the hydrogels tested, Huminsorb® Polyacrylate produced the most favorable outcomes, with treatment T9 (100\%, HP, 30 kg/ha) yielding 70.55 t/ha; this represented an increase of 11 t/ha as compared to the 100\% ETc treatment without hydrogel application. Moreover, the combination of hydrogel application with 50\% ETc water stress showed promising results, with treatment T4 (HP, 30 kg, 50\%) producing almost the same yield as the 100\% ETc treatment without hydrogel while saving 208 mm of water.},
  language  = {en}
}
@article{BaringhausGaigallThiele2018,
  author    = {Baringhaus, Ludwig and Gaigall, Daniel and Thiele, Jan Philipp},
  title     = {Statistical inference for L²-distances to uniformity},
  series = {Computational Statistics},
  volume    = {2018},
  journal   = {Computational Statistics},
  number    = {33},
  publisher = {Springer},
  address   = {Berlin},
  issn      = {1613-9658},
  doi       = {10.1007/s00180-018-0820-0},
  pages     = {1863 -- 1896},
  year      = {2018},
  abstract  = {The paper deals with the asymptotic behaviour of estimators, statistical tests and confidence intervals for L²-distances to uniformity based on the empirical distribution function, the integrated empirical distribution function and the integrated empirical survival function. Approximations of power functions, confidence intervals for the L²-distances and statistical neighbourhood-of-uniformity validation tests are obtained as main applications. The finite sample behaviour of the procedures is illustrated by a simulation study.},
  language  = {en}
}
@article{AbbasHedwigBalcetal.2023,
  author    = {Abbas, Karim and Hedwig, Lukas and Balc, Nicolae and Bremen, Sebastian},
  title     = {Advanced FFF of PEEK: Infill strategies and material characteristics for rapid tooling},
  series = {Polymers},
  volume    = {2023},
  journal   = {Polymers},
  number    = {15},
  publisher = {MDPI},
  address   = {Basel},
  doi       = {10.3390/polym15214293},
  pages     = {Artikel 4293},
  year      = {2023},
  abstract  = {Traditional vulcanization mold manufacturing is complex, costly, and under pressure due to shorter product lifecycles and diverse variations. Additive manufacturing using Fused Filament Fabrication and high-performance polymers like PEEK offer a promising future in this industry. This study assesses the compressive strength of various infill structures (honeycomb, grid, triangle, cubic, and gyroid) when considering two distinct build directions (Z, XY) to enhance PEEK's economic and resource efficiency in rapid tooling. A comparison with PETG samples shows the behavior of the infill strategies. Additionally, a proof of concept illustrates the application of a PEEK mold in vulcanization. A peak compressive strength of 135.6 MPa was attained in specimens that were 100\% solid and subjected to thermal post-treatment. This corresponds to a 20\% strength improvement in the Z direction. In terms of time and mechanical properties, the anisotropic grid and isotropic cubic infill have emerged for use in rapid tooling. Furthermore, the study highlights that reducing the layer thickness from 0.15 mm to 0.1 mm can result in a 15\% strength increase. The study unveils the successful utilization of a room-temperature FFF-printed PEEK mold in vulcanization injection molding. The parameters and infill strategies identified in this research enable the resource-efficient FFF printing of PEEK without compromising its strength properties. Using PEEK in rapid tooling allows a cost reduction of up to 70\% in tool production.},
  language  = {en}
}
@article{SchoeningBronderWuetal.2017,
  author    = {Sch{\"o}ning, Michael Josef and Bronder, Thomas and Wu, Chunsheng and Scheja, Sabrina and Jessing, Max and Metzger-Boddien, Christoph and Keusgen, Michael and Poghossian, Arshak},
  title     = {Label-Free DNA Detection with Capacitive Field-Effect Devices—Challenges and Opportunities},
  series = {Proceedings},
  volume    = {1},
  journal   = {Proceedings},
  number    = {8},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2504-3900},
  doi       = {10.3390/proceedings1080719},
  pages     = {Artikel 719},
  year      = {2017},
  abstract  = {Field-effect EIS (electrolyte-insulator-semiconductor) sensors modified with a positively charged weak polyelectrolyte layer have been applied for the electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge. The EIS sensors are able to detect the existence of target DNA amplicons in PCR (polymerase chain reaction) samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process. Due to their miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge, those sensors can serve as possible platform for the development of label-free DNA chips. Possible application fields as well as challenges and limitations will be discussed.},
  language  = {en}
}
@article{Gaigall2020,
  author    = {Gaigall, Daniel},
  title     = {Testing marginal homogeneity of a continuous bivariate distribution with possibly incomplete paired data},
  series = {Metrika},
  volume    = {2020},
  journal   = {Metrika},
  number    = {83},
  publisher = {Springer},
  issn      = {1435-926X},
  doi       = {10.1007/s00184-019-00742-5},
  pages     = {437 -- 465},
  year      = {2020},
  abstract  = {We discuss the testing problem of homogeneity of the marginal distributions of a continuous bivariate distribution based on a paired sample with possibly missing components (missing completely at random). Applying the well-known two-sample Cr{\´a}mer-von-Mises distance to the remaining data, we determine the limiting null distribution of our test statistic in this situation. It is seen that a new resampling approach is appropriate for the approximation of the unknown null distribution. We prove that the resulting test asymptotically reaches the significance level and is consistent. Properties of the test under local alternatives are pointed out as well. Simulations investigate the quality of the approximation and the power of the new approach in the finite sample case. As an illustration we apply the test to real data sets.},
  language  = {en}
}
@article{ScheerKapelyukhRodeetal.2015,
  author    = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland},
  title     = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model},
  series = {Drug Metabolism and Disposition},
  volume    = {43},
  journal   = {Drug Metabolism and Disposition},
  number    = {11},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-009x},
  doi       = {10.1124/dmd.115.065656},
  pages     = {1679 -- 1690},
  year      = {2015},
  language  = {en}
}
@article{RichterBraunsteinWinnardetal.2017,
  author    = {Richter, Charlotte and Braunstein, Bjoern and Winnard, Andrew and Nasser, Mona and Weber, T.},
  title     = {Human Biomechanical and Cardiopulmonary Responses to Partial Gravity - A Systematic Review},
  series = {Frontiers in physiology},
  journal   = {Frontiers in physiology},
  number    = {8, article 583},
  doi       = {10.3389/fphys.2017.00583},
  pages     = {22 Seiten},
  year      = {2017},
  language  = {en}
}
@article{FredebeulKreinSteingroever2014,
  author    = {Fredebeul-Krein, Markus and Steingr{\"o}ver, Markus},
  title     = {Wholesale broadband access to IPTV in an NGA environment : how to deal with it from a regulatory perspective?},
  series = {Telecommunications Policy},
  volume    = {38},
  journal   = {Telecommunications Policy},
  number    = {3},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0308-5961 (Print)},
  doi       = {doi:10.1016/j.telpol.2013.04.002},
  pages     = {264 -- 277},
  year      = {2014},
  language  = {en}
}
@article{PoghossianWeldenBuniatyanetal.2021,
  author    = {Poghossian, Arshak and Welden, Rene and Buniatyan, Vahe V. and Sch{\"o}ning, Michael Josef},
  title     = {An Array of On-Chip Integrated, Individually Addressable Capacitive Field-Effect Sensors with Control Gate: Design and Modelling},
  series = {Sensors},
  volume    = {21},
  journal   = {Sensors},
  number    = {18},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1424-8220},
  doi       = {10.3390/s21186161},
  pages     = {17},
  year      = {2021},
  abstract  = {The on-chip integration of multiple biochemical sensors based on field-effect electrolyte-insulator-semiconductor capacitors (EISCAP) is challenging due to technological difficulties in realization of electrically isolated EISCAPs on the same Si chip. In this work, we present a new simple design for an array of on-chip integrated, individually electrically addressable EISCAPs with an additional control gate (CG-EISCAP). The existence of the CG enables an addressable activation or deactivation of on-chip integrated individual CG-EISCAPs by simple electrical switching the CG of each sensor in various setups, and makes the new design capable for multianalyte detection without cross-talk effects between the sensors in the array. The new designed CG-EISCAP chip was modelled in so-called floating/short-circuited and floating/capacitively-coupled setups, and the corresponding electrical equivalent circuits were developed. In addition, the capacitance-voltage curves of the CG-EISCAP chip in different setups were simulated and compared with that of a single EISCAP sensor. Moreover, the sensitivity of the CG-EISCAP chip to surface potential changes induced by biochemical reactions was simulated and an impact of different parameters, such as gate voltage, insulator thickness and doping concentration in Si, on the sensitivity has been discussed.},
  language  = {en}
}
@article{VahidpourGuthmanArreolaetal.2022,
  author    = {Vahidpour, Farnoosh and Guthman, Eric and Arreola, Julia and Alghazali, Yousef H. M. and Wagner, Torsten and Sch{\"o}ning, Michael Josef},
  title     = {Assessment of Various Process Parameters for Optimized Sterilization Conditions Using a Multi-Sensing Platform},
  series = {Foods},
  volume    = {11},
  journal   = {Foods},
  number    = {5},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2304-8158},
  doi       = {10.3390/foods11050660},
  pages     = {Artikel 660},
  year      = {2022},
  abstract  = {In this study, an online multi-sensing platform was engineered to simultaneously evaluate various process parameters of food package sterilization using gaseous hydrogen peroxide (H₂O₂). The platform enabled the validation of critical aseptic parameters. In parallel, one series of microbiological count reduction tests was performed using highly resistant spores of B. atrophaeus DSM 675 to act as the reference method for sterility validation. By means of the multi-sensing platform together with microbiological tests, we examined sterilization process parameters to define the most effective conditions with regards to the highest spore kill rate necessary for aseptic packaging. As these parameters are mutually associated, a correlation between different factors was elaborated. The resulting correlation indicated the need for specific conditions regarding the applied H₂O₂ gas temperature, the gas flow and concentration, the relative humidity and the exposure time. Finally, the novel multi-sensing platform together with the mobile electronic readout setup allowed for the online and on-site monitoring of the sterilization process, selecting the best conditions for sterility and, at the same time, reducing the use of the time-consuming and costly microbiological tests that are currently used in the food package industry.},
  language  = {en}
}
@article{PoghossianKarschuckWagneretal.2022,
  author    = {Poghossian, Arshak and Karschuck, Tobias and Wagner, Patrick and Sch{\"o}ning, Michael Josef},
  title     = {Field-Effect Capacitors Decorated with Ligand-Stabilized Gold Nanoparticles: Modeling and Experiments},
  series = {Biosensors},
  volume    = {12},
  journal   = {Biosensors},
  number    = {5},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2079-6374},
  doi       = {10.3390/bios12050334},
  pages     = {Artikel 334},
  year      = {2022},
  abstract  = {Nanoparticles are recognized as highly attractive tunable materials for designing field-effect biosensors with enhanced performance. In this work, we present a theoretical model for electrolyte-insulator-semiconductor capacitors (EISCAP) decorated with ligand-stabilized charged gold nanoparticles. The charged AuNPs are taken into account as additional, nanometer-sized local gates. The capacitance-voltage (C-V) curves and constant-capacitance (ConCap) signals of the AuNP-decorated EISCAPs have been simulated. The impact of the AuNP coverage on the shift of the C-V curves and the ConCap signals was also studied experimentally on Al-p-Si-SiO₂ EISCAPs decorated with positively charged aminooctanethiol-capped AuNPs. In addition, the surface of the EISCAPs, modified with AuNPs, was characterized by scanning electron microscopy for different immobilization times of the nanoparticles.},
  language  = {en}
}
@article{FrohbergAnik1985,
  author    = {Frohberg, Martin G. and Anik, Sabri},
  title     = {The calculation of component activities of binary metallic melts from their gas solubilities},
  series = {Zeitschrift f{\"u}r Metallkunde},
  volume    = {76},
  journal   = {Zeitschrift f{\"u}r Metallkunde},
  number    = {2},
  issn      = {0044-3093},
  pages     = {135 -- 137},
  year      = {1985},
  language  = {en}
}
@article{DieringerRenzLindeletal.2011,
  author    = {Dieringer, Matthias A. and Renz, Wolfgang and Lindel, Tomasz D. and Seifert, Frank and Frauenrath, Tobias and von Knobelsdorf-Brenkenhoff, Florian and Waiczies, Helmar and Hoffmann, Werner and Rieger, Jan and Pfeiffer, Harald and Ittermann, Bernd and Schulz-Menger, Jeanette and Niendorf, Thoralf},
  title     = {Design and application of a four-channel transmit/receive surface coil for functional cardiac imaging at 7T},
  series = {Journal of Magnetic Resonance Imaging},
  volume    = {33},
  journal   = {Journal of Magnetic Resonance Imaging},
  number    = {3},
  publisher = {Wiley-Liss},
  address   = {New York},
  issn      = {1522-2586},
  doi       = {10.1002/jmri.22451},
  pages     = {736 -- 741},
  year      = {2011},
  abstract  = {Purpose To design and evaluate a four-channel cardiac transceiver coil array for functional cardiac imaging at 7T. Materials and Methods A four-element cardiac transceiver surface coil array was developed with two rectangular loops mounted on an anterior former and two rectangular loops on a posterior former. specific absorption rate (SAR) simulations were performed and a Burn:x-wiley:10531807:media:JMRI22451:tex2gif-stack-1 calibration method was applied prior to obtain 2D FLASH CINE (mSENSE, R = 2) images from nine healthy volunteers with a spatial resolution of up to 1 × 1 × 2.5 mm3. Results Tuning and matching was found to be better than 10 dB for all subjects. The decoupling (S21) was measured to be >18 dB between neighboring loops, >20 dB for opposite loops, and >30 dB for other loop combinations. SAR values were well within the limits provided by the IEC. Imaging provided clinically acceptable signal homogeneity with an excellent blood-myocardium contrast applying the Burn:x-wiley:10531807:media:JMRI22451:tex2gif-stack-2 calibration approach. Conclusion A four-channel cardiac transceiver coil array for 7T was built, allowing for cardiac imaging with clinically acceptable signal homogeneity and an excellent blood-myocardium contrast. Minor anatomic structures, such as pericardium, mitral, and tricuspid valves and their apparatus, as well as trabeculae, were accurately delineated.},
  language  = {en}
}
@article{FayyaziSardarThomasetal.2023,
  author    = {Fayyazi, Mojgan and Sardar, Paramjotsingh and Thomas, Sumit Infent and Daghigh, Roonak and Jamali, Ali and Esch, Thomas and Kemper, Hans and Langari, Reza and Khayyam, Hamid},
  title     = {Artificial intelligence/machine learning in energy management systems, control, and optimization of hydrogen fuel cell vehicles},
  volume    = {15},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  doi       = {10.3390/su15065249},
  pages     = {38},
  year      = {2023},
  abstract  = {Environmental emissions, global warming, and energy-related concerns have accelerated the advancements in conventional vehicles that primarily use internal combustion engines. Among the existing technologies, hydrogen fuel cell electric vehicles and fuel cell hybrid electric vehicles may have minimal contributions to greenhouse gas emissions and thus are the prime choices for environmental concerns. However, energy management in fuel cell electric vehicles and fuel cell hybrid electric vehicles is a major challenge. Appropriate control strategies should be used for effective energy management in these vehicles. On the other hand, there has been significant progress in artificial intelligence, machine learning, and designing data-driven intelligent controllers. These techniques have found much attention within the community, and state-of-the-art energy management technologies have been developed based on them. This manuscript reviews the application of machine learning and intelligent controllers for prediction, control, energy management, and vehicle to everything (V2X) in hydrogen fuel cell vehicles. The effectiveness of data-driven control and optimization systems are investigated to evolve, classify, and compare, and future trends and directions for sustainability are discussed.},
  language  = {en}
}
@article{EgliAyerPeteretal.2010,
  author    = {Egli, Simon and Ayer, Fran{\c{c}}ois and Peter, Martina and Eilmann, Britta and Rigling, Andreas},
  title     = {Is forest mushroom productivity driven by tree growth? Results from a thinning experiment},
  series = {Annals of Forest Science},
  volume    = {67},
  journal   = {Annals of Forest Science},
  number    = {5},
  publisher = {Springer},
  address   = {Paris},
  issn      = {1286-4560 (Print)},
  doi       = {10.1051/forest/2010011},
  pages     = {509},
  year      = {2010},
  abstract  = {• Most of the edible forest mushrooms are mycorrhizal and depend on carbohydrates produced by the associated trees. Fruiting patterns of these fungi are not yet fully understood since climatic factors alone do not completely explain mushroom occurrence. • The objective of this study was to retrospectively find out if changing tree growth following an increment thinning has influenced the diversity patterns and productivity of associated forest mushrooms in the fungus reserve La Chan{\´e}az, Switzerland. • The results reveal a clear temporal relationship between the thinning, the growth reaction of trees and the reaction of the fungal community, especially for the ectomycorrhizal species. The tree-ring width of the formerly suppressed beech trees and the fruit body number increased after thinning, leading to a significantly positive correlation between fruit body numbers and tree-ring width. • Fruit body production was influenced by previous annual tree growth, the best accordance was found between fruit body production and the tree-ring width two years previously. • The results support the hypothesis that ectomycorrhizal fruit body production must be linked with the growth of the associated host trees. Moreover, the findings indicate the importance of including mycorrhizal fungi as important players when discussing a tree as a carbon source or sink.},
  language  = {en}
}
@article{DrummEmhardtKoketal.2020,
  author    = {Drumm, Christian and Emhardt, Selina N. and Kok, Ellen M. and Jarodzka, Halzka and Brand-Gruwel, Saskia and van Gog, Tamara},
  title     = {How Experts Adapt Their Gaze Behavior When Modeling a Task to Novices},
  series = {Cognitive science},
  volume    = {44},
  journal   = {Cognitive science},
  number    = {9},
  publisher = {Wiley},
  address   = {Weinheim},
  issn      = {1551-6709},
  doi       = {10.1111/cogs.12893},
  pages     = {26},
  year      = {2020},
  abstract  = {Domain experts regularly teach novice students how to perform a task. This often requires them to adjust their behavior to the less knowledgeable audience and, hence, to behave in a more didactic manner. Eye movement modeling examples (EMMEs) are a contemporary educational tool for displaying experts' (natural or didactic) problem-solving behavior as well as their eye movements to learners. While research on expert-novice communication mainly focused on experts' changes in explicit, verbal communication behavior, it is as yet unclear whether and how exactly experts adjust their nonverbal behavior. This study first investigated whether and how experts change their eye movements and mouse clicks (that are displayed in EMMEs) when they perform a task naturally versus teach a task didactically. Programming experts and novices initially debugged short computer codes in a natural manner. We first characterized experts' natural problem-solving behavior by contrasting it with that of novices. Then, we explored the changes in experts' behavior when being subsequently instructed to model their task solution didactically. Experts became more similar to novices on measures associated with experts' automatized processes (i.e., shorter fixation durations, fewer transitions between code and output per click on the run button when behaving didactically). This adaptation might make it easier for novices to follow or imitate the expert behavior. In contrast, experts became less similar to novices for measures associated with more strategic behavior (i.e., code reading linearity, clicks on run button) when behaving didactically.},
  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}
}