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The article presents the investigation of the seismic behaviour of a modern URM building located in the municipality of Finale Emilia in province of Modena, Northern Italy. The building is situated in the centre of the series of the 2012 Northern Italy earthquakes and has not suffered any damage during the earthquake series in 2012. The observed earthquake resistance of the building is compared with predicted resistances based on linear and nonlinear design approaches according to Eurocode. Furthermore, probabilistic analyses based on nonlinear calculation models taking into account scattering of the most relevant input parameters are carried out to identify their influence to the results and to derive fragility curves.
Seismic excited liquid filled tanks are subjected to extreme loading due to hydrodynamic pressures, which can lead to nonlinear stability failure of the thinwalled cylindrical tanks, as it is known from past earthquakes. A significant reduction of the seismically induced loads can be obtained by the application of base isolation systems, which have to be designed carefully with respect to the modified hydrodynamic behaviour of the tank in interaction with the liquid. For this reason a highly sophisticated fluid-structure interaction model has to be applied for a realistic simulation of the overall dynamic system. In the following, such a model is presented and compared with the results of simplified mathematical models for rigidly supported tanks. Finally, it is examined to what extent a simple mechanical model can represent the behaviour of a base isolated tank in case of seismic excitation
Ross, Jillian ; Plummer, Simon M. ; Rode, Anja ; Scheer, Nico ; Bower, Conrad C. ; Vogel, Ortwin ; Henderson, Colin J. ; Wolf, C. Roland ; Elcombe, Clifford R.
Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained.
Ross-Jones, J. ; Teumer, T. ; Capitain, C. ; Tippkötter, Nils ; Krause, M. J. ; Methner, F.-J. ; Rädle, M.
In most beers, producers strive to minimize haze to maximize visual appeal. To detect the formation of particulates, a measurement system for sub-micron particles is required. Beer haze is naturally occurring, composed of protein or polyphenol particles; in their early stage of growth their size is smaller than 2 µm. Microscopy analysis is time and resource intensive; alternatively, backscattering is an inexpensive option for detecting particle sizes of interest.
Rossi, Leonardo ; Parisi, Davide ; Casari, Chiara ; Montanari, Luca ; Ruggieri, Gabriella ; Holtschoppen, Britta ; Butenweg, Christoph
Rossi, Leonardo ; Stupazzini, Marco ; Parisi, Davide ; Holtschoppen, Britta ; Ruggieri, Gabriella ; Butenweg, Christoph
The 2012 Emilia-Romagna earthquake, that mainly struck the homonymous Italian region provoking 28 casualties and damage to thousands of structures and infrastructures, is an exceptional source of information to question, investigate, and challenge the validity of seismic fragility functions and loss curves from an empirical standpoint. Among the most recent seismic events taking place in Europe, that of Emilia-Romagna is quite likely one of the best documented, not only in terms of experienced damages, but also for what concerns occurred losses and necessary reconstruction costs. In fact, in order to manage the compensations in a fair way both to citizens and business owners, soon after the seismic sequence, the regional administrative authority started (1) collecting damage and consequence-related data, (2) evaluating information sources and (3) taking care of the cross-checking of various reports. A specific database—so-called Sistema Informativo Gestione Europa (SFINGE)—was devoted to damaged business activities. As a result, 7 years after the seismic events, scientists can rely on a one-of-a-kind, vast and consistent database, containing information about (among other things): (1) buildings’ location and dimensions, (2) occurred structural damages, (3) experienced direct economic losses and (4) related reconstruction costs. The present work is focused on a specific data subset of SFINGE, whose elements are Long-Span-Beam buildings (mostly precast) deployed for business activities in industry, trade or agriculture. With the available set of data, empirical fragility functions, cost and loss ratio curves are elaborated, that may be included within existing Performance Based Earthquake Engineering assessment toolkits.
Monte Carlo Tree Search (MCTS) is a search technique that in the last decade emerged as a major breakthrough for Artificial Intelligence applications regarding board- and video-games. In 2016, AlphaGo, an MCTS-based software agent, outperformed the human world champion of the board game Go. This game was for long considered almost infeasible for machines, due to its immense search space and the need for a long-term strategy. Since this historical success, MCTS is considered as an effective new approach for many other scientific and technical problems. Interestingly, civil structural engineering, as a discipline, offers many tasks whose solution may benefit from intelligent search and in particular from adopting MCTS as a search tool. In this work, we show how MCTS can be adapted to search for suitable solutions of a structural engineering design problem. The problem consists of choosing the load-bearing elements in a reference reinforced concrete structure, so to achieve a set of specific dynamic characteristics. In the paper, we report the results obtained by applying both a plain and a hybrid version of single-agent MCTS. The hybrid approach consists of an integration of both MCTS and classic Genetic Algorithm (GA), the latter also serving as a term of comparison for the results. The study’s outcomes may open new perspectives for the adoption of MCTS as a design tool for civil engineers.
Characterization and evaluation of lignocellulosic biomass 130 hydrolysates for ABE fermentation
(2016)
Enzymatic hydrolysis of lignocellulosic material plays an important role in the classical biorefinery approach. Apart from the pretreatment of the raw material, hydrolysis is the basis for the conversion of the cellulose and hemicellulose fraction into fermentable sugars. After hydrolysis, usually a solid-liquid separation takes place, in order to separate the residual plant material from the sugar-rich fraction, which can be subsequently used in a fermentation step. In order to factor out the separation step, the usage of in alginate immobilized crude cellulose fiber beads (CFBs) were evaluated. Pretreated cellulose fibers are incorporated in an alginate matrix together with the relevant enzymes. In doing so, sugars diffuse trough the alginate matrix, allowing a simplified delivery into the surrounding fluid. This again reduces product inhibition of the glucose on the enzyme catalysts. By means of standardized bead production the hydrolysis in lab scale was possible. First results show that liberation of glucose and xylose is possible, allowing a maximum total sugar yield of 75 %.
Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium
(2016)
Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹.
Hydrogen is playing an increasingly important role in research and politics as an energy carrier of the future. Since hydrogen has commonly been produced from methane by steam reforming, the need for climate-friendly, alternative production routes is emerging. In addition to electrolysis, fermentative routes for the production of so-called biohydrogen are "green" alternatives. The application of microorganisms offers the advantage of sustainable production from renewable resources using easily manageable technologies. In this project, the hyperthermophilic, anaerobic microorganism Thermotoga neapolitana is used for the productio nof biohydrogen from renewable resources. The enzymatically hydrolyzed resources were used in fermentation leading to yield coefficients of 1.8 mole H₂ per mole glucose when using hydrolyzed straw and ryegrass supplemented with medium, respectively. These results are similar to the hydrogen yields when using Thermotoga basal medium with glucose (TBGY) as control group. In order to minimize the supplementation of the hydrolysate and thus increase the economic efficiency of the process, the essential media components were identified. The experiments revealed NaCl, KCl, and glucose as essential components for cell growth as well as biohydrogen production. When excluding NaCl, a decrease of 96% in hydrogen production occured.
The 2nd edition of the lightning risk management
standard (IEC 62305-2) considers structures, which may
endanger environment. In these cases, the loss is not limited to
the structure itself, which is valid for usual structures. In the past
(Edition 1) this danger was simply taken into account by a special
hazard factor, multiplying the existing risk for the structure with
a number. Now, in the edition 2, we add to the risk for the
structure itself a “second risk” due to the losses outside the
structure. The losses outside can be treated independently from
what occurs inside. This is a major advantage to analyze the risk
for sensitive structures, like chemical plants, nuclear plants, or
structures containing explosives, etc. In this paper, the existing
procedure given by the European version EN 62305-2 Ed.2 is
further developed and applied to a few structures.
In many cities, diesel buses are being replaced by electric buses with the aim of reducing local emissions and thus improving air quality. The protection of the environment and the health of the population is the highest priority of our society. For the transport companies that operate these buses, not only ecological issues but also economic issues are of great importance. Due to the high purchase costs of electric buses compared to conventional buses, operators are forced to use electric vehicles in a targeted manner in order to ensure amortization over the service life of the vehicles. A compromise between ecology and economy must be found in order to both protect the environment and ensure economical operation of the buses.
In this study, we present a new methodology for optimizing the vehicles’ charging time as a function of the parameters CO₂eq emissions and electricity costs. Based on recorded driving profiles in daily bus operation, the energy demands of conventional and electric buses are calculated for the passenger transportation in the city of Aachen in 2017. Different charging scenarios are defined to analyze the influence of the temporal variability of CO₂eq intensity and electricity price on the environmental impact and economy of the bus. For every individual day of a year, charging periods with the lowest and highest costs and emissions are identified and recommendations for daily bus operation are made. To enable both the ecological and economical operation of the bus, the parameters of electricity price and CO₂ are weighted differently, and several charging periods are proposed, taking into account the priorities previously set. A sensitivity analysis is carried out to evaluate the influence of selected parameters and to derive recommendations for improving the ecological and economic balance of the battery-powered electric vehicle.
In all scenarios, the optimization of the charging period results in energy cost savings of a maximum of 13.6% compared to charging at a fixed electricity price. The savings potential of CO₂eq emissions is similar, at 14.9%. From an economic point of view, charging between 2 a.m. and 4 a.m. results in the lowest energy costs on average. The CO₂eq intensity is also low in this period, but midday charging leads to the largest savings in CO₂eq emissions. From a life cycle perspective, the electric bus is not economically competitive with the conventional bus. However, from an ecological point of view, the electric bus saves on average 37.5% CO₂eq emissions over its service life compared to the diesel bus. The reduction potential is maximized if the electric vehicle exclusively consumes electricity from solar and wind power.
Heavy-duty trucks are one of the main contributors to greenhouse gas emissions in German traffic. Drivetrain electrification is an option to reduce tailpipe emissions by increasing energy conversion efficiency. To evaluate the vehicle’s environmental impacts, it is necessary to consider the entire life cycle. In addition to the daily use, it is also necessary to include the impact of production and disposal. This study presents the comparative life cycle analysis of a parallel hybrid and a conventional heavy-duty truck in long-haul operation. Assuming a uniform vehicle glider, only the differing parts of both drivetrains are taken into account to calculate the environmental burdens of the production. The use phase is modeled by a backward simulation in MATLAB/Simulink considering a characteristic driving cycle. A break-even analysis is conducted to show at what mileage the larger CO2eq emissions due to the production of the electric drivetrain are compensated. The effect of parameter variation on the break-even mileage is investigated by a sensitivity analysis. The results of this analysis show the difference in CO2eq/t km is negative, indicating that the hybrid vehicle releases 4.34 g CO2eq/t km over a lifetime fewer emissions compared to the diesel truck. The break-even analysis also emphasizes the advantages of the electrified drivetrain, compensating the larger emissions generated during production after already a distance of 15,800 km (approx. 1.5 months of operation time). The intersection coordinates, distance, and CO2eq, strongly depend on fuel, emissions for battery production and the driving profile, which lead to nearly all parameter variations showing an increase in break-even distance.
Röhlen, Desiree ; Pilas, Johanna ; Dahmen, Markus ; Keusgen, Michael ; Selmer, Thorsten ; Schöning, Michael Josef
Monitoring of organic acids (OA) and volatile fatty acids (VFA) is crucial for the control of anaerobic digestion. In case of unstable process conditions, an accumulation of these intermediates occurs. In the present work, two different enzyme-based biosensor arrays are combined and presented for facile electrochemical determination of several process-relevant analytes. Each biosensor utilizes a platinum sensor chip (14 × 14 mm²) with five individual working electrodes. The OA biosensor enables simultaneous measurement of ethanol, formate, d- and l-lactate, based on a bi-enzymatic detection principle. The second VFA biosensor provides an amperometric platform for quantification of acetate and propionate, mediated by oxidation of hydrogen peroxide. The cross-sensitivity of both biosensors toward potential interferents, typically present in fermentation samples, was investigated. The potential for practical application in complex media was successfully demonstrated in spiked sludge samples collected from three different biogas plants. Thereby, the results obtained by both of the biosensors were in good agreement to the applied reference measurements by photometry and gas chromatography, respectively. The proposed hybrid biosensor system was also used for long-term monitoring of a lab-scale biogas reactor (0.01 m³) for a period of 2 months. In combination with typically monitored parameters, such as gas quality, pH and FOS/TAC (volatile organic acids/total anorganic carbonate), the amperometric measurements of OA and VFA concentration could enhance the understanding of ongoing fermentation processes.
Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.
Rösch, C. ; Kratz, F. ; Hering, T. ; Trautmann, S. ; Umanskaya, N. ; Tippkötter, Nils ; Müller-Renno, C.M. ; Ulber, Roland ; Hannig, M. ; Ziegler, C.
The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase.
Röthenbacher, Annika ; Cesari, Matteo ; Doppler, Christopher E.J. ; Okkels, Niels ; Willemsen, Nele ; Sembowski, Nora ; Seger, Aline ; Lindner, Marie ; Brune, Corinna ; Stefani, Ambra ; Högl, Birgit ; Bialonski, Stephan ; Borghammer, Per ; Fink, Gereon R. ; Schober, Martin ; Sommerauer, Michael
REM sleep without atonia (RSWA) is a key feature for the diagnosis of rapid eye movement (REM) sleep behaviour disorder (RBD). We introduce RBDtector, a novel open-source software to score RSWA according to established SINBAR visual scoring criteria. We assessed muscle activity of the mentalis, flexor digitorum superficialis (FDS), and anterior tibialis (AT) muscles. RSWA was scored manually as tonic, phasic, and any activity by human scorers as well as using RBDtector in 20 subjects. Subsequently, 174 subjects (72 without RBD and 102 with RBD) were analysed with RBDtector to show the algorithm’s applicability. We additionally compared RBDtector estimates to a previously published dataset. RBDtector showed robust conformity with human scorings. The highest congruency was achieved for phasic and any activity of the FDS. Combining mentalis any and FDS any, RBDtector identified RBD subjects with 100% specificity and 96% sensitivity applying a cut-off of 20.6%. Comparable performance was obtained without manual artefact removal. RBD subjects also showed muscle bouts of higher amplitude and longer duration. RBDtector provides estimates of tonic, phasic, and any activity comparable to human scorings. RBDtector, which is freely available, can help identify RBD subjects and provides reliable RSWA metrics.
Ambitious climate targets affect the competitiveness of industries in the international market. To prevent such industries from moving to other countries in the wake of increased climate protection efforts, cost adjustments may become necessary. Their design requires knowledge of country-specific production costs. Here, we present country-specific cost figures for different production routes of steel, paying particular attention to transportation costs. The data can be used in floor price models aiming to assess the competitiveness of different steel production routes in different countries (Rübbelke, 2022).
The European Union's aim to become climate neutral by 2050 necessitates ambitious efforts to reduce carbon emissions. Large reductions can be attained particularly in energy intensive sectors like iron and steel. In order to prevent the relocation of such industries outside the EU in the course of tightening environmental regulations, the establishment of a climate club jointly with other large emitters and alternatively the unilateral implementation of an international cross-border carbon tax mechanism are proposed. This article focuses on the latter option choosing the steel sector as an example. In particular, we investigate the financial conditions under which a European cross border mechanism is capable to protect hydrogen-based steel production routes employed in Europe against more polluting competition from abroad. By using a floor price model, we assess the competitiveness of different steel production routes in selected countries. We evaluate the climate friendliness of steel production on the basis of specific GHG emissions. In addition, we utilize an input-output price model. It enables us to assess impacts of rising cost of steel production on commodities using steel as intermediates. Our results raise concerns that a cross-border tax mechanism will not suffice to bring about competitiveness of hydrogen-based steel production in Europe because the cost tends to remain higher than the cost of steel production in e.g. China. Steel is a classic example for a good used mainly as intermediate for other products. Therefore, a cross-border tax mechanism for steel will increase the price of products produced in the EU that require steel as an input. This can in turn adversely affect competitiveness of these sectors. Hence, the effects of higher steel costs on European exports should be borne in mind and could require the cross-border adjustment mechanism to also subsidize exports.
The Inverted Rotary Pendulum: Facilitating Practical Teaching in Advanced Control Engineering
(2024)
This paper outlines a practical approach to teach control engineering principles, with an inverted rotary pendulum, serving as an illustrative example. It shows how the pendulum is embedded in an advanced course of control engineering. This approach is incorporated into a flipped-classroom concept, as well as classical teaching concepts, offering students practical experience in control engineering. In addition, the design of the pendulum is shown, using a Raspberry Pi as the target platform for Matlab Simulink. This pendulum can be used in the classroom to evaluate the controller design mentioned above. It is analysed if the use of the pendulum generates a deeper understanding of the learning contents.
Sabitova, A. ; Ebert, Ph. ; Lenz, A. ; Schaafhausen, S. ; Ivanova, L. ; Dähne, M. ; Hoffmann, A. ; Dunin-Borkowski, R. E. ; Förster, Arnold ; Grandidier, B. ; Eisele, H.
Design and Development of a Novel Self-Igniting Microwave Plasma Jet for Industrial Applications
(2019)
Sadykov, Rustam ; Digel, Ilya ; Temiz Artmann, Aysegül ; Porst, Dariusz ; Linder, Peter ; Kayser, Peter ; Artmann, Gerhard ; Savitskaya, Irina ; Zhubanova, Azhar
Sajatovic, Miodrag ; Rihacek, Christoph ; Haindl, Bernhard ; Schnell, Michael ; Brandes, Sinja ; Gligorevic, Snjezana
A solid-state amperometric hydrogen sensor based on a protonated Nafion membrane and catalytic active electrode operating at room temperature was fabricated and tested. Ionic conducting polymer-metal electrode interfaces were prepared chemically by using the impregnation-reduction method. The polymer membrane was impregnated with tetra-ammine platinum chloride hydrate and the metal ions were subsequently reduced by using either sodium tetrahydroborate or potassium tetrahydroborate. The hydrogen sensing characteristics with air as reference gas is reported. The sensors were capable of detecting hydrogen concentrations from 10 ppm to 10% in nitrogen. The response time was in the range of 10-30 s and a stable linear current output was observed. The thin Pt films were characterized by XRD, Infrared Spectroscopy, Optical Microscopy, Atomic Force Microscopy, Scanning Electron Microscopy and EDAX.
Salpati, Laurent ; Chu, Xiaoyan ; Chen, Liangfu ; Prasad, Bhagwat ; Dallas, Shannon ; Evers, Raymond ; Mamaril-Fishman, Donna ; Geier, Ethan G. ; Kehler, Jonathan ; Kunta, Jeevan ; Mezler, Mario ; Laplanche, Loic ; Pang, Jodie ; Soars, Matthew G. ; Unadkat, Jashvant D. ; van Waterschoot, Robert A.B. ; Yabut, Jocelyn ; Schinkel, Alfred H. ; Scheer, Nico ; Rode, Anja
Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.
Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.