@article{HaegerBongaertsSiegert2022, author = {Haeger, Gerrit and Bongaerts, Johannes and Siegert, Petra}, title = {A convenient ninhydrin assay in 96-well format for amino acid-releasing enzymes using an air-stable reagent}, series = {Analytical Biochemistry}, journal = {Analytical Biochemistry}, number = {624}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1096-0309}, doi = {10.1016/j.ab.2022.114819}, pages = {Artikel 114819}, year = {2022}, abstract = {An improved and convenient ninhydrin assay for aminoacylase activity measurements was developed using the commercial EZ Nin™ reagent. Alternative reagents from literature were also evaluated and compared. The addition of DMSO to the reagent enhanced the solubility of Ruhemann's purple (RP). Furthermore, we found that the use of a basic, aqueous buffer enhances stability of RP. An acidic protocol for the quantification of lysine was developed by addition of glacial acetic acid. The assay allows for parallel processing in a 96-well format with measurements microtiter plates.}, language = {en} } @article{EilmannDobbertinRigling2013, author = {Eilmann, Britta and Dobbertin, Matthias and Rigling, Andreas}, title = {Growth response of Scots pine with different crown transparency status to drought release}, series = {Annals of Forest Science}, volume = {70}, journal = {Annals of Forest Science}, number = {7}, publisher = {Springer}, address = {Cham}, issn = {1286-4560 (Print)}, doi = {10.1007/s13595-013-0310-z}, pages = {685 -- 693}, year = {2013}, language = {en} } @article{StiemerThomaBraun2023, author = {Stiemer, Luc Nicolas and Thoma, Andreas and Braun, Carsten}, title = {MBT3D: Deep learning based multi-object tracker for bumblebee 3D flight path estimation}, series = {PLoS ONE}, volume = {18}, journal = {PLoS ONE}, number = {9}, publisher = {PLOS}, address = {San Fancisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0291415}, pages = {e0291415}, year = {2023}, abstract = {This work presents the Multi-Bees-Tracker (MBT3D) algorithm, a Python framework implementing a deep association tracker for Tracking-By-Detection, to address the challenging task of tracking flight paths of bumblebees in a social group. While tracking algorithms for bumblebees exist, they often come with intensive restrictions, such as the need for sufficient lighting, high contrast between the animal and background, absence of occlusion, significant user input, etc. Tracking flight paths of bumblebees in a social group is challenging. They suddenly adjust movements and change their appearance during different wing beat states while exhibiting significant similarities in their individual appearance. The MBT3D tracker, developed in this research, is an adaptation of an existing ant tracking algorithm for bumblebee tracking. It incorporates an offline trained appearance descriptor along with a Kalman Filter for appearance and motion matching. Different detector architectures for upstream detections (You Only Look Once (YOLOv5), Faster Region Proposal Convolutional Neural Network (Faster R-CNN), and RetinaNet) are investigated in a comparative study to optimize performance. The detection models were trained on a dataset containing 11359 labeled bumblebee images. YOLOv5 reaches an Average Precision of AP = 53, 8\%, Faster R-CNN achieves AP = 45, 3\% and RetinaNet AP = 38, 4\% on the bumblebee validation dataset, which consists of 1323 labeled bumblebee images. The tracker's appearance model is trained on 144 samples. The tracker (with Faster R-CNN detections) reaches a Multiple Object Tracking Accuracy MOTA = 93, 5\% and a Multiple Object Tracking Precision MOTP = 75, 6\% on a validation dataset containing 2000 images, competing with state-of-the-art computer vision methods. The framework allows reliable tracking of different bumblebees in the same video stream with rarely occurring identity switches (IDS). MBT3D has much lower IDS than other commonly used algorithms, with one of the lowest false positive rates, competing with state-of-the-art animal tracking algorithms. The developed framework reconstructs the 3-dimensional (3D) flight paths of the bumblebees by triangulation. It also handles and compares two alternative stereo camera pairs if desired.}, language = {en} } @article{SchierenKleinschmidtSchmutzetal.2019, author = {Schieren, Mark and Kleinschmidt, Joris and Schmutz, Axel and Loop, Torsten and Gatzweiler, Karl-Heinz and Staat, Manfred and Wappler, Frank and Defosse, Jerome}, title = {Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study}, series = {Anaesthesia}, volume = {74}, journal = {Anaesthesia}, number = {12}, publisher = {Wiley-Blackwell}, address = {Oxford}, isbn = {1365-2044}, doi = {10.1111/anae.14815}, year = {2019}, language = {en} } @article{GrandeMeffertSchoenbergeretal.2012, author = {Grande, Marion and Meffert, Elisabeth and Schoenberger, Eva and Jung, Stefanie and Frauenrath, Tobias and Huber, Walter and Hussmann, Katja and Moormann, Mareike and Heim, Stefan}, title = {From a concept to a word in a syntactically complete sentence: An fMRI study on spontaneous language production in an overt picture description task}, series = {NeuroImage}, volume = {61}, journal = {NeuroImage}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1522-2586}, doi = {10.1016/j.neuroimage.2012.03.087}, pages = {702 -- 714}, year = {2012}, abstract = {Spontaneous language has rarely been subjected to neuroimaging studies. This study therefore introduces a newly developed method for the analysis of linguistic phenomena observed in continuous language production during fMRI. Most neuroimaging studies investigating language have so far focussed on single word or — to a smaller extent — sentence processing, mostly due to methodological considerations. Natural language production, however, is far more than the mere combination of words to larger units. Therefore, the present study aimed at relating brain activation to linguistic phenomena like word-finding difficulties or syntactic completeness in a continuous language fMRI paradigm. A picture description task with special constraints was used to provoke hesitation phenomena and speech errors. The transcribed speech sample was segmented into events of one second and each event was assigned to one category of a complex schema especially developed for this purpose. The main results were: conceptual planning engages bilateral activation of the precuneus. Successful lexical retrieval is accompanied - particularly in comparison to unsolved word-finding difficulties - by the left middle and superior temporal gyrus. Syntactic completeness is reflected in activation of the left inferior frontal gyrus (IFG) (area 44). In sum, the method has proven to be useful for investigating the neural correlates of lexical and syntactic phenomena in an overt picture description task. This opens up new prospects for the analysis of spontaneous language production during fMRI.}, language = {en} } @article{Staat2021, author = {Staat, Manfred}, title = {An extension strain type Mohr-Coulomb criterion}, series = {Rock mechanics and rock engineering}, volume = {54}, journal = {Rock mechanics and rock engineering}, number = {12}, publisher = {Springer Nature}, address = {Cham}, issn = {1434-453X}, doi = {10.1007/s00603-021-02608-7}, pages = {6207 -- 6233}, year = {2021}, abstract = {Extension fractures are typical for the deformation under low or no confining pressure. They can be explained by a phenomenological extension strain failure criterion. In the past, a simple empirical criterion for fracture initiation in brittle rock has been developed. In this article, it is shown that the simple extension strain criterion makes unrealistic strength predictions in biaxial compression and tension. To overcome this major limitation, a new extension strain criterion is proposed by adding a weighted principal shear component to the simple criterion. The shear weight is chosen, such that the enriched extension strain criterion represents the same failure surface as the Mohr-Coulomb (MC) criterion. Thus, the MC criterion has been derived as an extension strain criterion predicting extension failure modes, which are unexpected in the classical understanding of the failure of cohesive-frictional materials. In progressive damage of rock, the most likely fracture direction is orthogonal to the maximum extension strain leading to dilatancy. The enriched extension strain criterion is proposed as a threshold surface for crack initiation CI and crack damage CD and as a failure surface at peak stress CP. Different from compressive loading, tensile loading requires only a limited number of critical cracks to cause failure. Therefore, for tensile stresses, the failure criteria must be modified somehow, possibly by a cut-off corresponding to the CI stress. Examples show that the enriched extension strain criterion predicts much lower volumes of damaged rock mass compared to the simple extension strain criterion.}, language = {en} } @article{YoshinobuMiyamotoWagneretal.2024, author = {Yoshinobu, Tatsuo and Miyamoto, Ko-ichiro and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Field-effect sensors combined with the scanned light pulse technique: from artificial olfactory images to chemical imaging technologies}, series = {Chemosensors}, volume = {12}, journal = {Chemosensors}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2227-9040}, doi = {10.3390/chemosensors12020020}, pages = {Artikel 20}, year = {2024}, abstract = {The artificial olfactory image was proposed by Lundstr{\"o}m et al. in 1991 as a new strategy for an electronic nose system which generated a two-dimensional mapping to be interpreted as a fingerprint of the detected gas species. The potential distribution generated by the catalytic metals integrated into a semiconductor field-effect structure was read as a photocurrent signal generated by scanning light pulses. The impact of the proposed technology spread beyond gas sensing, inspiring the development of various imaging modalities based on the light addressing of field-effect structures to obtain spatial maps of pH distribution, ions, molecules, and impedance, and these modalities have been applied in both biological and non-biological systems. These light-addressing technologies have been further developed to realize the position control of a faradaic current on the electrode surface for localized electrochemical reactions and amperometric measurements, as well as the actuation of liquids in microfluidic devices.}, language = {en} } @article{WeldenJablonskiWegeetal.2021, author = {Welden, Rene and Jablonski, Melanie and Wege, Christina and Keusgen, Michael and Wagner, Patrick Hermann and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Light-Addressable Actuator-Sensor Platform for Monitoring and Manipulation of pH Gradients in Microfluidics: A Case Study with the Enzyme Penicillinase}, series = {Biosensors}, volume = {11}, journal = {Biosensors}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2079-6374}, doi = {10.3390/bios11060171}, pages = {Artikel 171}, year = {2021}, abstract = {The feasibility of light-addressed detection and manipulation of pH gradients inside an electrochemical microfluidic cell was studied. Local pH changes, induced by a light-addressable electrode (LAE), were detected using a light-addressable potentiometric sensor (LAPS) with different measurement modes representing an actuator-sensor system. Biosensor functionality was examined depending on locally induced pH gradients with the help of the model enzyme penicillinase, which had been immobilized in the microfluidic channel. The surface morphology of the LAE and enzyme-functionalized LAPS was studied by scanning electron microscopy. Furthermore, the penicillin sensitivity of the LAPS inside the microfluidic channel was determined with regard to the analyte's pH influence on the enzymatic reaction rate. In a final experiment, the LAE-controlled pH inhibition of the enzyme activity was monitored by the LAPS.}, language = {en} } @article{AkimbekovDigelTastambeketal.2021, author = {Akimbekov, Nuraly S. and Digel, Ilya and Tastambek, Kuanysh T. and Sherelkhan, Dinara K. and Jussupova, Dariya B. and Altynbay, Nazym P.}, title = {Low-rank coal as a source of humic substances for soil amendment and fertility management}, series = {Agriculture}, volume = {11}, journal = {Agriculture}, number = {12}, publisher = {MDPI}, address = {Basel}, issn = {2077-0472}, doi = {10.3390/agriculture11121261}, pages = {25 Seiten}, year = {2021}, abstract = {Humic substances (HS), as important environmental components, are essential to soil health and agricultural sustainability. The usage of low-rank coal (LRC) for energy generation has declined considerably due to the growing popularity of renewable energy sources and gas. However, their potential as soil amendment aimed to maintain soil quality and productivity deserves more recognition. LRC, a highly heterogeneous material in nature, contains large quantities of HS and may effectively help to restore the physicochemical, biological, and ecological functionality of soil. Multiple emerging studies support the view that LRC and its derivatives can positively impact the soil microclimate, nutrient status, and organic matter turnover. Moreover, the phytotoxic effects of some pollutants can be reduced by subsequent LRC application. Broad geographical availability, relatively low cost, and good technical applicability of LRC offer the advantage of easy fulfilling soil amendment and conditioner requirements worldwide. This review analyzes and emphasizes the potential of LRC and its numerous forms/combinations for soil amelioration and crop production. A great benefit would be a systematic investment strategy implicating safe utilization and long-term application of LRC for sustainable agricultural production.}, language = {en} } @article{AkimbekovDigelTastambeketal.2022, author = {Akimbekov, Nuraly S. and Digel, Ilya and Tastambek, Kuanysh T. and Marat, Adel K. and Turaliyeva, Moldir A. and Kaiyrmanova, Gulzhan K.}, title = {Biotechnology of Microorganisms from Coal Environments: From Environmental Remediation to Energy Production}, series = {Biology}, volume = {11}, journal = {Biology}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {2079-7737}, doi = {10.3390/biology11091306}, pages = {47 Seiten}, year = {2022}, abstract = {It was generally believed that coal sources are not favorable as live-in habitats for microorganisms due to their recalcitrant chemical nature and negligible decomposition. However, accumulating evidence has revealed the presence of diverse microbial groups in coal environments and their significant metabolic role in coal biogeochemical dynamics and ecosystem functioning. The high oxygen content, organic fractions, and lignin-like structures of lower-rank coals may provide effective means for microbial attack, still representing a greatly unexplored frontier in microbiology. Coal degradation/conversion technology by native bacterial and fungal species has great potential in agricultural development, chemical industry production, and environmental rehabilitation. Furthermore, native microalgal species can offer a sustainable energy source and an excellent bioremediation strategy applicable to coal spill/seam waters. Additionally, the measures of the fate of the microbial community would serve as an indicator of restoration progress on post-coal-mining sites. This review puts forward a comprehensive vision of coal biodegradation and bioprocessing by microorganisms native to coal environments for determining their biotechnological potential and possible applications.}, language = {en} } @article{NiedermeierPennerUsherovichetal.2023, author = {Niedermeier, Jana and Penner, Crystal and Usherovich, Samuel and B{\´e}langer-Champagne, Camille and Paulßen, Elisabeth and Hoehr, Cornelia}, title = {Optical Fibers as Dosimeter Detectors for Mixed Proton/Neutron Fields - A Biological Dosimeter}, series = {electronics}, volume = {12}, journal = {electronics}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2079-9292}, doi = {10.3390/electronics12020324}, pages = {11 Seiten}, year = {2023}, abstract = {In recent years, proton therapy has gained importance as a cancer treatment modality due to its conformality with the tumor and the sparing of healthy tissue. However, in the interaction of the protons with the beam line elements and patient tissues, potentially harmful secondary neutrons are always generated. To ensure that this neutron dose is as low as possible, treatment plans could be created to also account for and minimize the neutron dose. To monitor such a treatment plan, a compact, easy to use, and inexpensive dosimeter must be developed that not only measures the physical dose, but which can also distinguish between proton and neutron contributions. To that end, plastic optical fibers with scintillation materials (Gd₂O₂S:Tb, Gd₂O₂S:Eu, and YVO₄:Eu) were irradiated with protons and neutrons. It was confirmed that sensors with different scintillation materials have different sensitivities to protons and neutrons. A combination of these three scintillators can be used to build a detector array to create a biological dosimeter.}, language = {en} } @article{BiewendtBoehnertBlaschke2020, author = {Biewendt, Marcel and B{\"o}hnert, Arno and Blaschke, Florian}, title = {The repercussions of the digital twin in the automotive industry on the new marketing logic}, series = {European Journal of Marketing and Economics}, volume = {4}, journal = {European Journal of Marketing and Economics}, number = {1}, publisher = {Revistia}, address = {London}, issn = {2601-8659}, doi = {10.26417/229eim64f}, pages = {68 -- 73}, year = {2020}, abstract = {Rapid development of virtual and data acquisition technology makes Digital Twin Technology (DT) one of the fundamental areas of research, while DT is one of the most promissory developments for the achievement of Industry 4.0. 48\% percent of organisations implementing the Internet of Things are already using DT or plan to use DT in 2020. The global market for DT is expected to grow by 38 percent annually, reaching USD16 billion by 2023. In addition, the number of participating organisations using digital twins is expected to triple by 2022. DTs are characterised by the integration between physical and virtual spaces. The driving idea for DT is to develop, test and build our devices in a virtual environment. The objective of this paper is to study the impact of DT in the automotive industry on the new marketing logic. This paper outlines the current challenges and possible directions for the future DT in marketing. This paper will be helpful for managers in the industry to use the advantages and potentials of DT.}, language = {en} } @article{BaringhausGaigall2017, author = {Baringhaus, Ludwig and Gaigall, Daniel}, title = {On Hotelling's T² test in a special paired sample case}, series = {Communications in Statistics - Theory and Methods}, volume = {48}, journal = {Communications in Statistics - Theory and Methods}, number = {2}, publisher = {Taylor \& Francis}, address = {London}, issn = {1532-415X}, doi = {10.1080/03610926.2017.1408828}, pages = {257 -- 267}, year = {2017}, abstract = {In a special paired sample case, Hotelling's T² test based on the differences of the paired random vectors is the likelihood ratio test for testing the hypothesis that the paired random vectors have the same mean; with respect to a special group of affine linear transformations it is the uniformly most powerful invariant test for the general alternative of a difference in mean. We present an elementary straightforward proof of this result. The likelihood ratio test for testing the hypothesis that the covariance structure is of the assumed special form is derived and discussed. Applications to real data are given.}, language = {en} } @article{LuisierLempiaeinenScherbichleretal.2014, author = {Luisier, Rapha{\"e}lle and Lempi{\"a}inen, Harri and Scherbichler, Nina and Braeuning, Albert and Geissler, Miriam and Dubost, Valerie and M{\"u}ller, Arne and Scheer, Nico and Chibout, Salah-Dine and Hara, Hisanori and Picard, Frank and Theil, Diethilde and Couttet, Philippe and Vitobello, Antonio and Grenet, Olivier and Grasl-Kraupp, Bettina and Ellinger-Ziegelbauer, Heidrung and Thomson, John P. and Meehan, Richard R. and Elcombe, Clifford R. and Henderson, Colin J. and Wolf, C. Roland and Schwarz, Michael and Moulin, Pierre and Terranova, Remi and Moggs, Jonathan G.}, title = {Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors}, series = {Toxicological Sciences}, volume = {139}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {https://doi.org/10.1093/toxsci/kfu038}, pages = {501 -- 511}, year = {2014}, abstract = {The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.}, language = {en} } @article{BlockViebahnJungbluth2024, author = {Block, Simon and Viebahn, Peter and Jungbluth, Christian}, title = {Analysing direct air capture for enabling negative emissions in Germany: an assessment of the resource requirements and costs of a potential rollout in 2045}, series = {Frontiers in Climate}, volume = {6}, journal = {Frontiers in Climate}, publisher = {Frontiers}, address = {Lausanne}, issn = {2624-9553}, doi = {10.3389/fclim.2024.1353939}, pages = {18 Seiten}, year = {2024}, abstract = {Direct air capture (DAC) combined with subsequent storage (DACCS) is discussed as one promising carbon dioxide removal option. The aim of this paper is to analyse and comparatively classify the resource consumption (land use, renewable energy and water) and costs of possible DAC implementation pathways for Germany. The paths are based on a selected, existing climate neutrality scenario that requires the removal of 20 Mt of carbon dioxide (CO2) per year by DACCS from 2045. The analysis focuses on the so-called "low-temperature" DAC process, which might be more advantageous for Germany than the "high-temperature" one. In four case studies, we examine potential sites in northern, central and southern Germany, thereby using the most suitable renewable energies for electricity and heat generation. We show that the deployment of DAC results in large-scale land use and high energy needs. The land use in the range of 167-353 km2 results mainly from the area required for renewable energy generation. The total electrical energy demand of 14.4 TWh per year, of which 46\% is needed to operate heat pumps to supply the heat demand of the DAC process, corresponds to around 1.4\% of Germany's envisaged electricity demand in 2045. 20 Mt of water are provided yearly, corresponding to 40\% of the city of Cologne's water demand (1.1 million inhabitants). The capture of CO2 (DAC) incurs levelised costs of 125-138 EUR per tonne of CO2, whereby the provision of the required energy via photovoltaics in southern Germany represents the lowest value of the four case studies. This does not include the costs associated with balancing its volatility. Taking into account transporting the CO2 via pipeline to the port of Wilhelmshaven, followed by transporting and sequestering the CO2 in geological storage sites in the Norwegian North Sea (DACCS), the levelised costs increase to 161-176 EUR/tCO2. Due to the longer transport distances from southern and central Germany, a northern German site using wind turbines would be the most favourable.}, language = {en} } @article{BhattaraiStaat2018, author = {Bhattarai, Aroj and Staat, Manfred}, title = {Computational comparison of different textile implants to correct apical prolapse in females}, series = {Current Directions in Biomedical Engineering}, volume = {4}, journal = {Current Directions in Biomedical Engineering}, number = {1}, publisher = {De Gruyter}, address = {Berlin}, doi = {10.1515/cdbme-2018-0159}, pages = {661 -- 664}, year = {2018}, abstract = {Prosthetic textile implants of different shapes, sizes and polymers are used to correct the apical prolapse after hysterectomy (removal of the uterus). The selection of the implant before or during minimally invasive surgery depends on the patient's anatomical defect, intended function after reconstruction and most importantly the surgeon's preference. Weakness or damage of the supporting tissues during childbirth, menopause or previous pelvic surgeries may put females in higher risk of prolapse. Numerical simulations of reconstructed pelvic floor with weakened tissues and organ supported by textile product models: DynaMesh®-PRS soft, DynaMesh®-PRP soft and DynaMesh®-CESA from FEG Textiletechnik mbH, Germany are compared.}, language = {en} } @article{BragardConradvanHoeketal.2011, author = {Bragard, Michael and Conrad, M. and van Hoek, H. and De Doncker, R. W.}, title = {The integrated emitter turn-off thyristor (IETO) : an innovative thyristor-based high power semiconductor device using MOS assisted turn-off}, series = {IEEE transactions on industry applications}, volume = {47}, journal = {IEEE transactions on industry applications}, number = {5}, publisher = {IEEE}, address = {New York}, issn = {0093-9994}, doi = {10.1109/TIA.2011.2161432}, pages = {2175 -- 2182}, year = {2011}, language = {en} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {In humans, 75\% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80\% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15\%) and larger livers (20\%). Changes in hepatic morphology and a decreased blood glucose (30\%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.}, language = {en} } @article{Kleefeld2021, author = {Kleefeld, Andreas}, title = {The hot spots conjecture can be false: some numerical examples}, series = {Advances in Computational Mathematics}, volume = {47}, journal = {Advances in Computational Mathematics}, publisher = {Springer}, address = {Dordrecht}, issn = {1019-7168}, doi = {10.1007/s10444-021-09911-5}, year = {2021}, abstract = {The hot spots conjecture is only known to be true for special geometries. This paper shows numerically that the hot spots conjecture can fail to be true for easy to construct bounded domains with one hole. The underlying eigenvalue problem for the Laplace equation with Neumann boundary condition is solved with boundary integral equations yielding a non-linear eigenvalue problem. Its discretization via the boundary element collocation method in combination with the algorithm by Beyn yields highly accurate results both for the first non-zero eigenvalue and its corresponding eigenfunction which is due to superconvergence. Additionally, it can be shown numerically that the ratio between the maximal/minimal value inside the domain and its maximal/minimal value on the boundary can be larger than 1 + 10- 3. Finally, numerical examples for easy to construct domains with up to five holes are provided which fail the hot spots conjecture as well.}, language = {en} } @article{ScheerHendersonKapelyukhetal.2019, author = {Scheer, Nico and Henderson, Colin James and Kapelyukh, Yury and Rode, Anja and Mclaren, Aileen W. and MacLeod, Alastair Kenneth and Lin, De and Wright, Jayne and Stanley, Lesley and Wolf, C. Roland}, title = {An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials}, series = {Drug Metabolism and Disposition}, journal = {Drug Metabolism and Disposition}, number = {Early view}, doi = {10.1124/dmd.119.086397}, pages = {69 Seiten}, year = {2019}, language = {en} }