@inproceedings{6490, abstract = {Smart contracts are programs that are stored and executed on the Blockchain and can receive, manage and transfer money (cryptocurrency units). Two important problems regarding smart contracts are formal analysis and compiler optimization. Formal analysis is extremely important, because smart contracts hold funds worth billions of dollars and their code is immutable after deployment. Hence, an undetected bug can cause significant financial losses. Compiler optimization is also crucial, because every action of a smart contract has to be executed by every node in the Blockchain network. Therefore, optimizations in compiling smart contracts can lead to significant savings in computation, time and energy. Two classical approaches in program analysis and compiler optimization are intraprocedural and interprocedural analysis. In intraprocedural analysis, each function is analyzed separately, while interprocedural analysis considers the entire program. In both cases, the analyses are usually reduced to graph problems over the control flow graph (CFG) of the program. These graph problems are often computationally expensive. Hence, there has been ample research on exploiting structural properties of CFGs for efficient algorithms. One such well-studied property is the treewidth, which is a measure of tree-likeness of graphs. It is known that intraprocedural CFGs of structured programs have treewidth at most 6, whereas the interprocedural treewidth cannot be bounded. This result has been used as a basis for many efficient intraprocedural analyses. In this paper, we explore the idea of exploiting the treewidth of smart contracts for formal analysis and compiler optimization. First, similar to classical programs, we show that the intraprocedural treewidth of structured Solidity and Vyper smart contracts is at most 9. Second, for global analysis, we prove that the interprocedural treewidth of structured smart contracts is bounded by 10 and, in sharp contrast with classical programs, treewidth-based algorithms can be easily applied for interprocedural analysis. Finally, we supplement our theoretical results with experiments using a tool we implemented for computing treewidth of smart contracts and show that the treewidth is much lower in practice. We use 36,764 real-world Ethereum smart contracts as benchmarks and find that they have an average treewidth of at most 3.35 for the intraprocedural case and 3.65 for the interprocedural case. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Goharshady, Ehsan Kafshdar}, booktitle = {Proceedings of the 34th ACM Symposium on Applied Computing}, isbn = {9781450359337}, location = {Limassol, Cyprus}, pages = {400--408}, publisher = {ACM}, title = {{The treewidth of smart contracts}}, doi = {10.1145/3297280.3297322}, volume = {Part F147772}, year = {2019}, } @article{7158, abstract = {Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, and so on. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, and so on. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in an important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect we consider is that the control flow graphs for most programs have constant treewidth. Our main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing but can answer subsequent queries significantly faster as compared to the current algorithmic solutions for interprocedural dataflow analysis. We have also implemented our algorithms and evaluated their performance for performing on-demand interprocedural dataflow analysis on various domains, such as for live variable analysis and reaching definitions, on a standard benchmark set. Our experimental results align with our theoretical statements and show that after a lightweight preprocessing, on-demand queries are answered much faster than the standard existing algorithmic approaches. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Goyal, Prateesh and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, issn = {0164-0925}, journal = {ACM Transactions on Programming Languages and Systems}, number = {4}, publisher = {ACM}, title = {{Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth}}, doi = {10.1145/3363525}, volume = {41}, year = {2019}, } @article{7014, abstract = {We study the problem of developing efficient approaches for proving worst-case bounds of non-deterministic recursive programs. Ranking functions are sound and complete for proving termination and worst-case bounds of nonrecursive programs. First, we apply ranking functions to recursion, resulting in measure functions. We show that measure functions provide a sound and complete approach to prove worst-case bounds of non-deterministic recursive programs. Our second contribution is the synthesis of measure functions in nonpolynomial forms. We show that non-polynomial measure functions with logarithm and exponentiation can be synthesized through abstraction of logarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem using linear programming. While previous methods obtain worst-case polynomial bounds, our approach can synthesize bounds of the form $\mathcal{O}(n\log n)$ as well as $\mathcal{O}(n^r)$ where $r$ is not an integer. We present experimental results to demonstrate that our approach can obtain efficiently worst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the divide-and-conquer algorithm for the Closest-Pair problem, where we obtain $\mathcal{O}(n \log n)$ worst-case bound, and (ii) Karatsuba's algorithm for polynomial multiplication and Strassen's algorithm for matrix multiplication, where we obtain $\mathcal{O}(n^r)$ bound such that $r$ is not an integer and close to the best-known bounds for the respective algorithms.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar}, journal = {ACM Transactions on Programming Languages and Systems}, number = {4}, publisher = {ACM}, title = {{Non-polynomial worst-case analysis of recursive programs}}, doi = {10.1145/3339984}, volume = {41}, year = {2019}, } @article{6486, abstract = {Based on a novel control scheme, where a steady modification of the streamwise velocity profile leads to complete relaminarization of initially fully turbulent pipe flow, we investigate the applicability and usefulness of custom-shaped honeycombs for such control. The custom-shaped honeycombs are used as stationary flow management devices which generate specific modifications of the streamwise velocity profile. Stereoscopic particle image velocimetry and pressure drop measurements are used to investigate and capture the development of the relaminarizing flow downstream these devices. We compare the performance of straight (constant length across the radius of the pipe) honeycombs with custom-shaped ones (variable length across the radius) and try to determine the optimal shape for maximal relaminarization at minimal pressure loss. The optimally modified streamwise velocity profile is found to be M-shaped, and the maximum attainable Reynolds number for total relaminarization is found to be of the order of 10,000. Consequently, the respective reduction in skin friction downstream of the device is almost by a factor of 5. The break-even point, where the additional pressure drop caused by the device is balanced by the savings due to relaminarization and a net gain is obtained, corresponds to a downstream stretch of distances as low as approximately 100 pipe diameters of laminar flow.}, author = {Kühnen, Jakob and Scarselli, Davide and Hof, Björn}, issn = {1528901X}, journal = {Journal of Fluids Engineering}, number = {11}, publisher = {ASME}, title = {{Relaminarization of pipe flow by means of 3D-printed shaped honeycombs}}, doi = {10.1115/1.4043494}, volume = {141}, year = {2019}, } @article{6228, abstract = {Following the recent observation that turbulent pipe flow can be relaminarised bya relatively simple modification of the mean velocity profile, we here carry out aquantitative experimental investigation of this phenomenon. Our study confirms thata flat velocity profile leads to a collapse of turbulence and in order to achieve theblunted profile shape, we employ a moving pipe segment that is briefly and rapidlyshifted in the streamwise direction. The relaminarisation threshold and the minimumshift length and speeds are determined as a function of Reynolds number. Althoughturbulence is still active after the acceleration phase, the modulated profile possessesa severely decreased lift-up potential as measured by transient growth. As shown,this results in an exponential decay of fluctuations and the flow relaminarises. Whilethis method can be easily applied at low to moderate flow speeds, the minimumstreamwise length over which the acceleration needs to act increases linearly with theReynolds number.}, author = {Scarselli, Davide and Kühnen, Jakob and Hof, Björn}, issn = {14697645}, journal = {Journal of Fluid Mechanics}, pages = {934--948}, publisher = {Cambridge University Press}, title = {{Relaminarising pipe flow by wall movement}}, doi = {10.1017/jfm.2019.191}, volume = {867}, year = {2019}, } @article{6260, abstract = {Polar auxin transport plays a pivotal role in plant growth and development. PIN auxin efflux carriers regulate directional auxin movement by establishing local auxin maxima, minima, and gradients that drive multiple developmental processes and responses to environmental signals. Auxin has been proposed to modulate its own transport by regulating subcellular PIN trafficking via processes such as clathrin-mediated PIN endocytosis and constitutive recycling. Here, we further investigated the mechanisms by which auxin affects PIN trafficking by screening auxin analogs and identified pinstatic acid (PISA) as a positive modulator of polar auxin transport in Arabidopsis thaliana. PISA had an auxin-like effect on hypocotyl elongation and adventitious root formation via positive regulation of auxin transport. PISA did not activate SCFTIR1/AFB signaling and yet induced PIN accumulation at the cell surface by inhibiting PIN internalization from the plasma membrane. This work demonstrates PISA to be a promising chemical tool to dissect the regulatory mechanisms behind subcellular PIN trafficking and auxin transport.}, author = {Oochi, A and Hajny, Jakub and Fukui, K and Nakao, Y and Gallei, Michelle C and Quareshy, M and Takahashi, K and Kinoshita, T and Harborough, SR and Kepinski, S and Kasahara, H and Napier, RM and Friml, Jiří and Hayashi, KI}, issn = {1532-2548}, journal = {Plant Physiology}, number = {2}, pages = {1152--1165}, publisher = {ASPB}, title = {{Pinstatic acid promotes auxin transport by inhibiting PIN internalization}}, doi = {10.1104/pp.19.00201}, volume = {180}, year = {2019}, } @article{6508, abstract = {Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation.}, author = {Shamipour, Shayan and Kardos, Roland and Xue, Shi-lei and Hof, Björn and Hannezo, Edouard B and Heisenberg, Carl-Philipp J}, issn = {10974172}, journal = {Cell}, number = {6}, pages = {1463--1479.e18}, publisher = {Elsevier}, title = {{Bulk actin dynamics drive phase segregation in zebrafish oocytes}}, doi = {10.1016/j.cell.2019.04.030}, volume = {177}, year = {2019}, } @article{7001, author = {Schwayer, Cornelia and Shamipour, Shayan and Pranjic-Ferscha, Kornelija and Schauer, Alexandra and Balda, M and Tada, M and Matter, K and Heisenberg, Carl-Philipp J}, issn = {1097-4172}, journal = {Cell}, number = {4}, pages = {937--952.e18}, publisher = {Cell Press}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.1016/j.cell.2019.10.006}, volume = {179}, year = {2019}, } @phdthesis{6891, abstract = {While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. Cells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. Nevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. Therefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. The results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. Thus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. Thereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance. }, author = {Kopf, Aglaja}, isbn = {978-3-99078-002-2}, issn = {2663-337X}, keywords = {cell biology, immunology, leukocyte, migration, microfluidics}, pages = {171}, publisher = {Institute of Science and Technology Austria}, title = {{The implication of cytoskeletal dynamics on leukocyte migration}}, doi = {10.15479/AT:ISTA:6891}, year = {2019}, } @article{6328, abstract = {During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.}, author = {Renkawitz, Jörg and Kopf, Aglaja and Stopp, Julian A and de Vries, Ingrid and Driscoll, Meghan K. and Merrin, Jack and Hauschild, Robert and Welf, Erik S. and Danuser, Gaudenz and Fiolka, Reto and Sixt, Michael K}, journal = {Nature}, pages = {546--550}, publisher = {Springer Nature}, title = {{Nuclear positioning facilitates amoeboid migration along the path of least resistance}}, doi = {10.1038/s41586-019-1087-5}, volume = {568}, year = {2019}, }