@article{9647, abstract = {Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.}, author = {Petrov, Tatjana and Igler, Claudia and Sezgin, Ali and Henzinger, Thomas A and Guet, Calin C}, issn = {0304-3975}, journal = {Theoretical Computer Science}, pages = {1--16}, publisher = {Elsevier}, title = {{Long lived transients in gene regulation}}, doi = {10.1016/j.tcs.2021.05.023}, volume = {893}, year = {2021}, } @inproceedings{10108, abstract = {We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs.}, author = {Mühlböck, Fabian and Henzinger, Thomas A}, booktitle = {International Conference on Runtime Verification}, isbn = {978-3-030-88493-2}, issn = {1611-3349}, keywords = {run-time verification, software engineering, implicit specification}, location = {Virtual}, pages = {231--243}, publisher = {Springer Nature}, title = {{Differential monitoring}}, doi = {10.1007/978-3-030-88494-9_12}, volume = {12974}, year = {2021}, } @misc{9946, abstract = {We argue that the time is ripe to investigate differential monitoring, in which the specification of a program's behavior is implicitly given by a second program implementing the same informal specification. Similar ideas have been proposed before, and are currently implemented in restricted form for testing and specialized run-time analyses, aspects of which we combine. We discuss the challenges of implementing differential monitoring as a general-purpose, black-box run-time monitoring framework, and present promising results of a preliminary implementation, showing low monitoring overheads for diverse programs.}, author = {Mühlböck, Fabian and Henzinger, Thomas A}, issn = {2664-1690}, keywords = {run-time verification, software engineering, implicit specification}, pages = {17}, publisher = {IST Austria}, title = {{Differential monitoring}}, doi = {10.15479/AT:ISTA:9946}, year = {2021}, } @article{10404, abstract = {While convolutional neural networks (CNNs) have found wide adoption as state-of-the-art models for image-related tasks, their predictions are often highly sensitive to small input perturbations, which the human vision is robust against. This paper presents Perturber, a web-based application that allows users to instantaneously explore how CNN activations and predictions evolve when a 3D input scene is interactively perturbed. Perturber offers a large variety of scene modifications, such as camera controls, lighting and shading effects, background modifications, object morphing, as well as adversarial attacks, to facilitate the discovery of potential vulnerabilities. Fine-tuned model versions can be directly compared for qualitative evaluation of their robustness. Case studies with machine learning experts have shown that Perturber helps users to quickly generate hypotheses about model vulnerabilities and to qualitatively compare model behavior. Using quantitative analyses, we could replicate users’ insights with other CNN architectures and input images, yielding new insights about the vulnerability of adversarially trained models.}, author = {Sietzen, Stefan and Lechner, Mathias and Borowski, Judy and Hasani, Ramin and Waldner, Manuela}, issn = {1467-8659}, journal = {Computer Graphics Forum}, number = {7}, pages = {253--264}, publisher = {Wiley}, title = {{Interactive analysis of CNN robustness}}, doi = {10.1111/cgf.14418}, volume = {40}, year = {2021}, } @article{10674, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets.}, author = {Aghajohari, Milad and Avni, Guy and Henzinger, Thomas A}, issn = {1860-5974}, journal = {Logical Methods in Computer Science}, keywords = {computer science, computer science and game theory, logic in computer science}, number = {1}, pages = {10:1--10:23}, publisher = {International Federation for Computational Logic}, title = {{Determinacy in discrete-bidding infinite-duration games}}, doi = {10.23638/LMCS-17(1:10)2021}, volume = {17}, year = {2021}, }