@inproceedings{5948, abstract = {We study the termination problem for nondeterministic probabilistic programs. We consider the bounded termination problem that asks whether the supremum of the expected termination time over all schedulers is bounded. First, we show that ranking supermartingales (RSMs) are both sound and complete for proving bounded termination over nondeterministic probabilistic programs. For nondeterministic probabilistic programs a previous result claimed that RSMs are not complete for bounded termination, whereas our result corrects the previous flaw and establishes completeness with a rigorous proof. Second, we present the first sound approach to establish lower bounds on expected termination time through RSMs.}, author = {Fu, Hongfei and Chatterjee, Krishnendu}, booktitle = {International Conference on Verification, Model Checking, and Abstract Interpretation}, location = {Cascais, Portugal}, pages = {468--490}, publisher = {Springer Nature}, title = {{Termination of nondeterministic probabilistic programs}}, doi = {10.1007/978-3-030-11245-5_22}, volume = {11388}, year = {2019}, } @article{6014, abstract = {Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity.}, author = {Varshney, Atul and Steinberg, Victor}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Elastic alfven waves in elastic turbulence}}, doi = {10.1038/s41467-019-08551-0}, volume = {10}, year = {2019}, } @article{6022, abstract = {The evolution of new species is made easier when traits under divergent ecological selection are also mating cues. Such ecological mating cues are now considered more common than previously thought, but we still know little about the genetic changes underlying their evolution or more generally about the genetic basis for assortative mating behaviors. Both tight physical linkage and the existence of large-effect preference loci will strengthen genetic associations between behavioral and ecological barriers, promoting the evolution of assortative mating. The warning patterns of Heliconius melpomene and H. cydno are under disruptive selection due to increased predation of nonmimetic hybrids and are used during mate recognition. We carried out a genome-wide quantitative trait locus (QTL) analysis of preference behaviors between these species and showed that divergent male preference has a simple genetic basis. We identify three QTLs that together explain a large proportion (approximately 60%) of the difference in preference behavior observed between the parental species. One of these QTLs is just 1.2 (0-4.8) centiMorgans (cM) from the major color pattern gene optix, and, individually, all three have a large effect on the preference phenotype. Genomic divergence between H. cydno and H. melpomene is high but broadly heterogenous, and admixture is reduced at the preference-optix color pattern locus but not the other preference QTLs. The simple genetic architecture we reveal will facilitate the evolution and maintenance of new species despite ongoing gene flow by coupling behavioral and ecological aspects of reproductive isolation.}, author = {Merrill, Richard M. and Rastas, Pasi and Martin, Simon H. and Melo Hurtado, Maria C and Barker, Sarah and Davey, John and Mcmillan, W. Owen and Jiggins, Chris D.}, journal = {PLoS Biology}, number = {2}, publisher = {Public Library of Science}, title = {{Genetic dissection of assortative mating behavior}}, doi = {10.1371/journal.pbio.2005902}, volume = {17}, year = {2019}, } @article{6023, abstract = {Multicellular development requires coordinated cell polarization relative to body axes, and translation to oriented cell division 1–3 . In plants, it is unknown how cell polarities are connected to organismal axes and translated to division. Here, we identify Arabidopsis SOSEKI proteins that integrate apical–basal and radial organismal axes to localize to polar cell edges. Localization does not depend on tissue context, requires cell wall integrity and is defined by a transferrable, protein-specific motif. A Domain of Unknown Function in SOSEKI proteins resembles the DIX oligomerization domain in the animal Dishevelled polarity regulator. The DIX-like domain self-interacts and is required for edge localization and for influencing division orientation, together with a second domain that defines the polar membrane domain. Our work shows that SOSEKI proteins locally interpret global polarity cues and can influence cell division orientation. Furthermore, this work reveals that, despite fundamental differences, cell polarity mechanisms in plants and animals converge on a similar protein domain.}, author = {Yoshida, Saiko and Van Der Schuren, Alja and Van Dop, Maritza and Van Galen, Luc and Saiga, Shunsuke and Adibi, Milad and Möller, Barbara and Ten Hove, Colette A. and Marhavy, Peter and Smith, Richard and Friml, Jiří and Weijers, Dolf}, journal = {Nature Plants}, number = {2}, pages = {160--166}, publisher = {Springer Nature}, title = {{A SOSEKI-based coordinate system interprets global polarity cues in arabidopsis}}, doi = {10.1038/s41477-019-0363-6}, volume = {5}, year = {2019}, } @article{6025, abstract = {Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.}, author = {Capek, Daniel and Smutny, Michael and Tichy, Alexandra Madelaine and Morri, Maurizio and Janovjak, Harald L and Heisenberg, Carl-Philipp J}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration}}, doi = {10.7554/eLife.42093}, volume = {8}, year = {2019}, } @article{6028, abstract = {We give a construction allowing us to build local renormalized solutions to general quasilinear stochastic PDEs within the theory of regularity structures, thus greatly generalizing the recent results of [1, 5, 11]. Loosely speaking, our construction covers quasilinear variants of all classes of equations for which the general construction of [3, 4, 7] applies, including in particular one‐dimensional systems with KPZ‐type nonlinearities driven by space‐time white noise. In a less singular and more specific case, we furthermore show that the counterterms introduced by the renormalization procedure are given by local functionals of the solution. The main feature of our construction is that it allows exploitation of a number of existing results developed for the semilinear case, so that the number of additional arguments it requires is relatively small.}, author = {Gerencser, Mate and Hairer, Martin}, journal = {Communications on Pure and Applied Mathematics}, number = {9}, pages = {1983--2005}, publisher = {Wiley}, title = {{A solution theory for quasilinear singular SPDEs}}, doi = {10.1002/cpa.21816}, volume = {72}, year = {2019}, } @inproceedings{6035, abstract = {We present JuliaReach, a toolbox for set-based reachability analysis of dynamical systems. JuliaReach consists of two main packages: Reachability, containing implementations of reachability algorithms for continuous and hybrid systems, and LazySets, a standalone library that implements state-of-the-art algorithms for calculus with convex sets. The library offers both concrete and lazy set representations, where the latter stands for the ability to delay set computations until they are needed. The choice of the programming language Julia and the accompanying documentation of our toolbox allow researchers to easily translate set-based algorithms from mathematics to software in a platform-independent way, while achieving runtime performance that is comparable to statically compiled languages. Combining lazy operations in high dimensions and explicit computations in low dimensions, JuliaReach can be applied to solve complex, large-scale problems.}, author = {Bogomolov, Sergiy and Forets, Marcelo and Frehse, Goran and Potomkin, Kostiantyn and Schilling, Christian}, booktitle = {Proceedings of the 22nd International Conference on Hybrid Systems: Computation and Control}, isbn = {9781450362825}, keywords = {reachability analysis, hybrid systems, lazy computation}, location = {Montreal, QC, Canada}, pages = {39--44}, publisher = {ACM}, title = {{JuliaReach: A toolbox for set-based reachability}}, doi = {10.1145/3302504.3311804}, volume = {22}, year = {2019}, } @inproceedings{6042, abstract = {Static program analyzers are increasingly effective in checking correctness properties of programs and reporting any errors found, often in the form of error traces. However, developers still spend a significant amount of time on debugging. This involves processing long error traces in an effort to localize a bug to a relatively small part of the program and to identify its cause. In this paper, we present a technique for automated fault localization that, given a program and an error trace, efficiently narrows down the cause of the error to a few statements. These statements are then ranked in terms of their suspiciousness. Our technique relies only on the semantics of the given program and does not require any test cases or user guidance. In experiments on a set of C benchmarks, we show that our technique is effective in quickly isolating the cause of error while out-performing other state-of-the-art fault-localization techniques.}, author = {Christakis, Maria and Heizmann, Matthias and Mansur, Muhammad Numair and Schilling, Christian and Wüstholz, Valentin}, booktitle = {25th International Conference on Tools and Algorithms for the Construction and Analysis of Systems }, location = {Prague, Czech Republic}, pages = {226--243}, publisher = {Springer Nature}, title = {{Semantic fault localization and suspiciousness ranking}}, doi = {10.1007/978-3-030-17462-0_13}, volume = {11427}, year = {2019}, } @article{6046, abstract = {Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses.}, author = {Mitosch, Karin and Rieckh, Georg and Bollenbach, Mark Tobias}, journal = {Molecular systems biology}, number = {2}, publisher = {Embo Press}, title = {{Temporal order and precision of complex stress responses in individual bacteria}}, doi = {10.15252/msb.20188470}, volume = {15}, year = {2019}, } @article{6049, abstract = {In this article it is shown that large systems with many interacting units endowing multiple phases display self-oscillations in the presence of linear feedback between the control and order parameters, where an Andronov–Hopf bifurcation takes over the phase transition. This is simply illustrated through the mean field Landau theory whose feedback dynamics turn out to be described by the Van der Pol equation and it is then validated for the fully connected Ising model following heat bath dynamics. Despite its simplicity, this theory accounts potentially for a rich range of phenomena: here it is applied to describe in a stylized way (i) excess demand-price cycles due to strong herding in a simple agent-based market model; (ii) congestion waves in queuing networks triggered by user feedback to delays in overloaded conditions; and (iii) metabolic network oscillations resulting from cell growth control in a bistable phenotypic landscape.}, author = {De Martino, Daniele}, journal = {Journal of Physics A: Mathematical and Theoretical}, number = {4}, publisher = {IOP Publishing}, title = {{Feedback-induced self-oscillations in large interacting systems subjected to phase transitions}}, doi = {10.1088/1751-8121/aaf2dd}, volume = {52}, year = {2019}, } @article{6050, abstract = {We answer a question of David Hilbert: given two circles it is not possible in general to construct their centers using only a straightedge. On the other hand, we give infinitely many families of pairs of circles for which such construction is possible. }, author = {Akopyan, Arseniy and Fedorov, Roman}, journal = {Proceedings of the American Mathematical Society}, pages = {91--102}, publisher = {AMS}, title = {{Two circles and only a straightedge}}, doi = {10.1090/proc/14240}, volume = {147}, year = {2019}, } @article{6052, abstract = {Expansion microscopy is a relatively new approach to super-resolution imaging that uses expandable hydrogels to isotropically increase the physical distance between fluorophores in biological samples such as cell cultures or tissue slices. The classic gel recipe results in an expansion factor of ~4×, with a resolution of 60–80 nm. We have recently developed X10 microscopy, which uses a gel that achieves an expansion factor of ~10×, with a resolution of ~25 nm. Here, we provide a step-by-step protocol for X10 expansion microscopy. A typical experiment consists of seven sequential stages: (i) immunostaining, (ii) anchoring, (iii) polymerization, (iv) homogenization, (v) expansion, (vi) imaging, and (vii) validation. The protocol presented here includes recommendations for optimization, pitfalls and their solutions, and detailed guidelines that should increase reproducibility. Although our protocol focuses on X10 expansion microscopy, we detail which of these suggestions are also applicable to classic fourfold expansion microscopy. We exemplify our protocol using primary hippocampal neurons from rats, but our approach can be used with other primary cells or cultured cell lines of interest. This protocol will enable any researcher with basic experience in immunostainings and access to an epifluorescence microscope to perform super-resolution microscopy with X10. The procedure takes 3 d and requires ~5 h of actively handling the sample for labeling and expansion, and another ~3 h for imaging and analysis.}, author = {Truckenbrodt, Sven M and Sommer, Christoph M and Rizzoli, Silvio O and Danzl, Johann G}, journal = {Nature Protocols}, number = {3}, pages = {832–863}, publisher = {Nature Publishing Group}, title = {{A practical guide to optimization in X10 expansion microscopy}}, doi = {10.1038/s41596-018-0117-3}, volume = {14}, year = {2019}, } @article{6053, abstract = {Recent technical developments in the fields of quantum electromechanics and optomechanics have spawned nanoscale mechanical transducers with the sensitivity to measure mechanical displacements at the femtometre scale and the ability to convert electromagnetic signals at the single photon level. A key challenge in this field is obtaining strong coupling between motion and electromagnetic fields without adding additional decoherence. Here we present an electromechanical transducer that integrates a high-frequency (0.42 GHz) hypersonic phononic crystal with a superconducting microwave circuit. The use of a phononic bandgap crystal enables quantum-level transduction of hypersonic mechanical motion and concurrently eliminates decoherence caused by acoustic radiation. Devices with hypersonic mechanical frequencies provide a natural pathway for integration with Josephson junction quantum circuits, a leading quantum computing technology, and nanophotonic systems capable of optical networking and distributing quantum information.}, author = {Kalaee, Mahmoud and Mirhosseini, Mohammad and Dieterle, Paul B. and Peruzzo, Matilda and Fink, Johannes M and Painter, Oskar}, issn = {1748-3395}, journal = {Nature Nanotechnology}, number = {4}, pages = {334–339}, publisher = {Springer Nature}, title = {{Quantum electromechanics of a hypersonic crystal}}, doi = {10.1038/s41565-019-0377-2}, volume = {14}, year = {2019}, } @misc{6060, author = {Vicoso, Beatriz}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary data for "Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome" (Huylman, Toups et al., 2019). }}, doi = {10.15479/AT:ISTA:6060}, year = {2019}, } @misc{6062, abstract = {Open the files in Jupyter Notebook (reccomended https://www.anaconda.com/distribution/#download-section with Python 3.7).}, author = {Nardin, Michele}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary Code and Data for the paper "The Entorhinal Cognitive Map is Attracted to Goals"}}, doi = {10.15479/AT:ISTA:6062}, year = {2019}, } @article{6069, abstract = {Electron transport in two-dimensional conducting materials such as graphene, with dominant electron–electron interaction, exhibits unusual vortex flow that leads to a nonlocal current-field relation (negative resistance), distinct from the classical Ohm’s law. The transport behavior of these materials is best described by low Reynolds number hydrodynamics, where the constitutive pressure–speed relation is Stoke’s law. Here we report evidence of such vortices observed in a viscous flow of Newtonian fluid in a microfluidic device consisting of a rectangular cavity—analogous to the electronic system. We extend our experimental observations to elliptic cavities of different eccentricities, and validate them by numerically solving bi-harmonic equation obtained for the viscous flow with no-slip boundary conditions. We verify the existence of a predicted threshold at which vortices appear. Strikingly, we find that a two-dimensional theoretical model captures the essential features of three-dimensional Stokes flow in experiments.}, author = {Mayzel, Jonathan and Steinberg, Victor and Varshney, Atul}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Stokes flow analogous to viscous electron current in graphene}}, doi = {10.1038/s41467-019-08916-5}, volume = {10}, year = {2019}, } @misc{6074, abstract = {This dataset contains the supplementary data for the research paper "Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition". The contained files have the following content: 'Supplementary Figures.pdf' Additional figures (as referenced in the paper). 'Supplementary Table 1. Statistics.xlsx' Details on statistical tests performed in the paper. 'Supplementary Table 2. Differentially expressed gene analysis.xlsx' Results for the differential gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro (ESCs, EBs, NPCs; analysis with DESeq2) samples. 'Supplementary Table 3. Gene Ontology (GO) term enrichment analysis.xlsx' Results for the GO term enrichment analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro (GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro samples were split into upregulated and downregulated genes (up/down) and the analysis was performed on each subset (e.g. GO ESC up / GO ESC down). 'Supplementary Table 4. Differentially expressed gene analysis for CFC samples.xlsx' Results for the differential gene expression analysis for samples from adult mice before (HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively). Each sheet shows the results for a different comparison. Sheets 1-3 show results for comparisons between timepoints for wild type (WT) samples only and sheets 4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results for comparisons between genotypes at each time point and sheet 10 contains the results for the analysis of differential expression trajectories between wild type and mutant. 'Supplementary Table 5. Cluster identification.xlsx' Results for k-means clustering of genes by expression. Sheet 1 shows clustering of just the genes with significantly different expression trajectories between genotypes. Sheet 2 shows clustering of all genes that are significantly differentially expressed in any of the comparisons (includes also genes with same trajectories). 'Supplementary Table 6. GO term cluster analysis.xlsx' Results for the GO term enrichment analysis and EWCE analysis for enrichment of cell type specific genes for each cluster identified by clustering genes with different expression trajectories (see Table S5, sheet 1). 'Supplementary Table 7. Setd5 mass spectrometry results.xlsx' Results showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet 1 shows protein protein interaction data generated from these results (combined with data from the STRING database. Sheet 2 shows the results of the statistical analysis with limma. 'Supplementary Table 8. PolII ChIP-seq analysis.xlsx' Results for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows results for differential binding of PolII at the transcription start site (TSS) between genotypes and sheets 2+3 show the corresponding GO enrichment analysis for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with increased binding of PolII at the TSS.}, author = {Dotter, Christoph and Novarino, Gaia}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary data for the research paper "Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition"}}, doi = {10.15479/AT:ISTA:6074}, year = {2019}, } @article{6086, abstract = {We show that linear analytic cocycles where all Lyapunov exponents are negative infinite are nilpotent. For such one-frequency cocycles we show that they can be analytically conjugated to an upper triangular cocycle or a Jordan normal form. As a consequence, an arbitrarily small analytic perturbation leads to distinct Lyapunov exponents. Moreover, in the one-frequency case where the th Lyapunov exponent is finite and the st negative infinite, we obtain a simple criterion for domination in which case there is a splitting into a nilpotent part and an invertible part.}, author = {Sadel, Christian and Xu, Disheng}, journal = {Ergodic Theory and Dynamical Systems}, number = {4}, pages = {1082--1098}, publisher = {Cambridge University Press}, title = {{Singular analytic linear cocycles with negative infinite Lyapunov exponents}}, doi = {10.1017/etds.2017.52}, volume = {39}, year = {2019}, } @article{6087, abstract = {Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. Conversely, MPC specification is defective in taz−/− follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity.}, author = {Xia, Peng and Gütl, Daniel J and Zheden, Vanessa and Heisenberg, Carl-Philipp J}, journal = {Cell}, number = {6}, pages = {1379--1392.e14}, publisher = {Elsevier}, title = {{Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity}}, doi = {10.1016/j.cell.2019.01.019}, volume = {176}, year = {2019}, } @article{6088, abstract = {P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood–brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain diseases. In the present study, seven marketed drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib, and cyclosporine A) and one nonmarketed drug (tariquidar), with known in vitro ABCB1/ABCG2 inhibitory properties, were screened for their inhibitory potency at the BBB in vivo. Positron emission tomography (PET) using the model ABCB1/ABCG2 substrate [11C]erlotinib was performed in mice. Tested inhibitors were administered as i.v. bolus injections at 30 min before the start of the PET scan, followed by a continuous i.v. infusion for the duration of the PET scan. Five of the tested drugs increased total distribution volume of [11C]erlotinib in the brain (VT,brain) compared to vehicle-treated animals (tariquidar, + 69%; erlotinib, + 19% and +23% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 22%; lapatinib, + 25%; and cyclosporine A, + 49%). For all drugs, increases in [11C]erlotinib brain distribution were lower than in Abcb1a/b(−/−)Abcg2(−/−) mice (+149%), which suggested that only partial ABCB1/ABCG2 inhibition was reached at the mouse BBB. The plasma concentrations of the tested drugs at the time of the PET scan were higher than clinically achievable plasma concentrations. Some of the tested drugs led to significant increases in blood radioactivity concentrations measured at the end of the PET scan (erlotinib, + 103% and +113% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 125%; and cyclosporine A, + 101%), which was most likely caused by decreased hepatobiliary excretion of radioactivity. Taken together, our data suggest that some marketed tyrosine kinase inhibitors may be repurposed to inhibit ABCB1 and ABCG2 at the BBB. From a clinical perspective, moderate increases in brain delivery despite the administration of high i.v. doses as well as peripheral drug–drug interactions due to transporter inhibition in clearance organs question the translatability of this concept.}, author = {Traxl, Alexander and Mairinger, Severin and Filip, Thomas and Sauberer, Michael and Stanek, Johann and Poschner, Stefan and Jäger, Walter and Zoufal, Viktoria and Novarino, Gaia and Tournier, Nicolas and Bauer, Martin and Wanek, Thomas and Langer, Oliver}, journal = {Molecular Pharmaceutics}, number = {3}, pages = {1282--1293}, publisher = {American Chemical Society}, title = {{Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib}}, doi = {10.1021/acs.molpharmaceut.8b01217}, volume = {16}, year = {2019}, }