TY - JOUR AB - Flows through pipes and channels are, in practice, almost always turbulent, and the multiscale eddying motion is responsible for a major part of the encountered friction losses and pumping costs1. Conversely, for pulsatile flows, in particular for aortic blood flow, turbulence levels remain low despite relatively large peak velocities. For aortic blood flow, high turbulence levels are intolerable as they would damage the shear-sensitive endothelial cell layer2,3,4,5. Here we show that turbulence in ordinary pipe flow is diminished if the flow is driven in a pulsatile mode that incorporates all the key features of the cardiac waveform. At Reynolds numbers comparable to those of aortic blood flow, turbulence is largely inhibited, whereas at much higher speeds, the turbulent drag is reduced by more than 25%. This specific operation mode is more efficient when compared with steady driving, which is the present situation for virtually all fluid transport processes ranging from heating circuits to water, gas and oil pipelines. AU - Scarselli, Davide AU - Lopez Alonso, Jose M AU - Varshney, Atul AU - Hof, Björn ID - 14341 IS - 7977 JF - Nature SN - 0028-0836 TI - Turbulence suppression by cardiac-cycle-inspired driving of pipe flow VL - 621 ER - TY - JOUR AB - Purpose: Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype but with limited neuroradiological data and insufficient evidence for causality of the variants. Methods: Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays and a zebrafish model. Results: We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs, and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model. Conclusion: We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity. AU - Accogli, Andrea AU - Lin, Sheng-Jia AU - Severino, Mariasavina AU - Kim, Sung-Hoon AU - Huang, Kevin AU - Rocca, Clarissa AU - Landsverk, Megan AU - Zaki, Maha S. AU - Al-Maawali, Almundher AU - Srinivasan, Varunvenkat M. AU - Al-Thihli, Khalid AU - Schaefer, G. Bradly AU - Davis, Monica AU - Tonduti, Davide AU - Doneda, Chiara AU - Marten, Lara M. AU - Mühlhausen, Chris AU - Gomez, Maria AU - Lamantea, Eleonora AU - Mena, Rafael AU - Nizon, Mathilde AU - Procaccio, Vincent AU - Begtrup, Amber AU - Telegrafi, Aida AU - Cui, Hong AU - Schulz, Heidi L. AU - Mohr, Julia AU - Biskup, Saskia AU - Loos, Mariana Amina AU - Aráoz, Hilda Verónica AU - Salpietro, Vincenzo AU - Keppen, Laura Davis AU - Chitre, Manali AU - Petree, Cassidy AU - Raymond, Lucy AU - Vogt, Julie AU - Sawyer, Lindsey B. AU - Basinger, Alice A. AU - Pedersen, Signe Vandal AU - Pearson, Toni S. AU - Grange, Dorothy K. AU - Lingappa, Lokesh AU - McDunnah, Paige AU - Horvath, Rita AU - Cognè, Benjamin AU - Isidor, Bertrand AU - Hahn, Andreas AU - Gripp, Karen W. AU - Jafarnejad, Seyed Mehdi AU - Østergaard, Elsebet AU - Prada, Carlos E. AU - Ghezzi, Daniele AU - Gowda, Vykuntaraju K. AU - Taylor, Robert W. AU - Sonenberg, Nahum AU - Houlden, Henry AU - Sissler, Marie AU - Varshney, Gaurav K. AU - Maroofian, Reza ID - 14368 IS - 11 JF - Genetics in Medicine KW - Genetics (clinical) SN - 1098-3600 TI - Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder VL - 25 ER - TY - CONF AB - We formalized general (i.e., type-0) grammars using the Lean 3 proof assistant. We defined basic notions of rewrite rules and of words derived by a grammar, and used grammars to show closure of the class of type-0 languages under four operations: union, reversal, concatenation, and the Kleene star. The literature mostly focuses on Turing machine arguments, which are possibly more difficult to formalize. For the Kleene star, we could not follow the literature and came up with our own grammar-based construction. AU - Dvorak, Martin AU - Blanchette, Jasmin ID - 13120 SN - 9783959772846 T2 - 14th International Conference on Interactive Theorem Proving TI - Closure properties of general grammars - formally verified VL - 268 ER - TY - JOUR AB - Bundling crossings is a strategy which can enhance the readability of graph drawings. In this paper we consider good drawings, i.e., we require that any two edges have at most one common point which can be a common vertex or a crossing. Our main result is that there is a polynomial-time algorithm to compute an 8-approximation of the bundled crossing number of a good drawing with no toothed hole. In general the number of toothed holes has to be added to the 8-approximation. In the special case of circular drawings the approximation factor is 8, this improves upon the 10-approximation of Fink et al. [14]. Our approach also works with the same approximation factor for families of pseudosegments, i.e., curves intersecting at most once. We also show how to compute a 9/2-approximation when the intersection graph of the pseudosegments is bipartite and has no toothed hole. AU - Arroyo Guevara, Alan M AU - Felsner, Stefan ID - 13969 IS - 6 JF - Journal of Graph Algorithms and Applications SN - 1526-1719 TI - Approximating the bundled crossing number VL - 27 ER - TY - CONF AB - We study the Hamilton cycle problem with input a random graph G ~ G(n,p) in two different settings. In the first one, G is given to us in the form of randomly ordered adjacency lists while in the second one, we are given the adjacency matrix of G. In each of the two settings we derive a deterministic algorithm that w.h.p. either finds a Hamilton cycle or returns a certificate that such a cycle does not exist for p = p(n) ≥ 0. The running times of our algorithms are O(n) and respectively, each being best possible in its own setting. AU - Anastos, Michael ID - 14344 SN - 9781611977554 T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms TI - Fast algorithms for solving the Hamilton cycle problem with high probability VL - 2023 ER -