@article{5944, abstract = {Understanding the thermodynamics of the duplication process is a fundamental step towards a comprehensive physical theory of biological systems. However, the immense complexity of real cells obscures the fundamental tensions between energy gradients and entropic contributions that underlie duplication. The study of synthetic, feasible systems reproducing part of the key ingredients of living entities but overcoming major sources of biological complexity is of great relevance to deepen the comprehension of the fundamental thermodynamic processes underlying life and its prevalence. In this paper an abstract—yet realistic—synthetic system made of small synthetic protocell aggregates is studied in detail. A fundamental relation between free energy and entropic gradients is derived for a general, non-equilibrium scenario, setting the thermodynamic conditions for the occurrence and prevalence of duplication phenomena. This relation sets explicitly how the energy gradients invested in creating and maintaining structural—and eventually, functional—elements of the system must always compensate the entropic gradients, whose contributions come from changes in the translational, configurational, and macrostate entropies, as well as from dissipation due to irreversible transitions. Work/energy relations are also derived, defining lower bounds on the energy required for the duplication event to take place. A specific example including real ternary emulsions is provided in order to grasp the orders of magnitude involved in the problem. It is found that the minimal work invested over the system to trigger a duplication event is around ~ 10−13J , which results, in the case of duplication of all the vesicles contained in a liter of emulsion, in an amount of energy around ~ 1kJ . Without aiming to describe a truly biological process of duplication, this theoretical contribution seeks to explicitly define and identify the key actors that participate in it.}, author = {Corominas-Murtra, Bernat}, issn = {20751729}, journal = {Life}, number = {1}, publisher = {MDPI}, title = {{Thermodynamics of duplication thresholds in synthetic protocell systems}}, doi = {10.3390/life9010009}, volume = {9}, year = {2019}, } @article{6029, abstract = {Protein micropatterning has become an important tool for many biomedical applications as well as in academic research. Current techniques that allow to reduce the feature size of patterns below 1 μm are, however, often costly and require sophisticated equipment. We present here a straightforward and convenient method to generate highly condensed nanopatterns of proteins without the need for clean room facilities or expensive equipment. Our approach is based on nanocontact printing and allows for the fabrication of protein patterns with feature sizes of 80 nm and periodicities down to 140 nm. This was made possible by the use of the material X-poly(dimethylsiloxane) (X-PDMS) in a two-layer stamp layout for protein printing. In a proof of principle, different proteins at various scales were printed and the pattern quality was evaluated by atomic force microscopy (AFM) and super-resolution fluorescence microscopy.}, author = {Lindner, Marco and Tresztenyak, Aliz and Fülöp, Gergö and Jahr, Wiebke and Prinz, Adrian and Prinz, Iris and Danzl, Johann G and Schütz, Gerhard J. and Sevcsik, Eva}, issn = {22962646}, journal = {Frontiers in Chemistry}, publisher = {Frontiers Media S.A.}, title = {{A fast and simple contact printing approach to generate 2D protein nanopatterns}}, doi = {10.3389/fchem.2018.00655}, volume = {6}, 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{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{5945, abstract = {In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.}, author = {Petkova, Mariela D. and Tkacik, Gasper and Bialek, William and Wieschaus, Eric F. and Gregor, Thomas}, journal = {Cell}, number = {4}, pages = {844--855.e15}, publisher = {Cell Press}, title = {{Optimal decoding of cellular identities in a genetic network}}, doi = {10.1016/j.cell.2019.01.007}, volume = {176}, year = {2019}, } @article{5943, abstract = {The hairpin instability of a jet in a crossflow (JICF) for a low jet-to-crossflow velocity ratio is investigated experimentally for a velocity ratio range of R ∈ (0.14, 0.75) and crossflow Reynolds numbers ReD ∈ (260, 640). From spectral analysis we characterize the Strouhal number and amplitude of the hairpin instability as a function of R and ReD. We demonstrate that the dynamics of the hairpins is well described by the Landau model, and, hence, that the instability occurs through Hopf bifurcation, similarly to other hydrodynamical oscillators such as wake behind different bluff bodies. Using the Landau model, we determine the precise threshold values of hairpin shedding. We also study the spatial dependence of this hydrodynamical instability, which shows a global behaviour.}, author = {Klotz, Lukasz and Gumowski, Konrad and Wesfreid, José Eduardo}, journal = {Journal of Fluid Mechanics}, pages = {386--406}, publisher = {Cambridge University Press}, title = {{Experiments on a jet in a crossflow in the low-velocity-ratio regime}}, doi = {10.1017/jfm.2018.974}, volume = {863}, 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}, } @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}, } @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{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}, }