@article{10363, abstract = {Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.}, author = {Lee, Jungmin and Vernet, Andyna and Gruber, Nathalie and Kready, Kasia M. and Burrill, Devin R. and Way, Jeffrey C. and Silver, Pamela A.}, issn = {1741-0134}, journal = {Protein Engineering, Design and Selection}, publisher = {Oxford University Press}, title = {{Rational engineering of an erythropoietin fusion protein to treat hypoxia}}, doi = {10.1093/protein/gzab025}, volume = {34}, year = {2021}, } @article{10809, abstract = {Thermoelectric materials are engines that convert heat into an electrical current. Intuitively, the efficiency of this process depends on how many electrons (charge carriers) can move and how easily they do so, how much energy those moving electrons transport, and how easily the temperature gradient is maintained. In terms of material properties, an excellent thermoelectric material requires a high electrical conductivity σ, a high Seebeck coefficient S (a measure of the induced thermoelectric voltage as a function of temperature gradient), and a low thermal conductivity κ. The challenge is that these three properties are strongly interrelated in a conflicting manner (1). On page 722 of this issue, Roychowdhury et al. (2) have found a way to partially break these ties in silver antimony telluride (AgSbTe2) with the addition of cadmium (Cd) cations, which increase the ordering in this inherently disordered thermoelectric material.}, author = {Liu, Yu and Ibáñez, Maria}, issn = {1095-9203}, journal = {Science}, number = {6530}, pages = {678--679}, publisher = {American Association for the Advancement of Science}, title = {{Tidying up the mess}}, doi = {10.1126/science.abg0886}, volume = {371}, year = {2021}, } @article{8317, abstract = {When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with one or several holes to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special “basic” holes guarantee foldability.}, author = {Aichholzer, Oswin and Akitaya, Hugo A. and Cheung, Kenneth C. and Demaine, Erik D. and Demaine, Martin L. and Fekete, Sándor P. and Kleist, Linda and Kostitsyna, Irina and Löffler, Maarten and Masárová, Zuzana and Mundilova, Klara and Schmidt, Christiane}, issn = {1879-081X}, journal = {Computational Geometry: Theory and Applications}, publisher = {Elsevier}, title = {{Folding polyominoes with holes into a cube}}, doi = {10.1016/j.comgeo.2020.101700}, volume = {93}, year = {2021}, } @unpublished{10912, abstract = {Brain dynamics display collective phenomena as diverse as neuronal oscillations and avalanches. Oscillations are rhythmic, with fluctuations occurring at a characteristic scale, whereas avalanches are scale-free cascades of neural activity. Here we show that such antithetic features can coexist in a very generic class of adaptive neural networks. In the most simple yet fully microscopic model from this class we make direct contact with human brain resting-state activity recordings via tractable inference of the model's two essential parameters. The inferred model quantitatively captures the dynamics over a broad range of scales, from single sensor fluctuations, collective behaviors of nearly-synchronous extreme events on multiple sensors, to neuronal avalanches unfolding over multiple sensors across multiple time-bins. Importantly, the inferred parameters correlate with model-independent signatures of "closeness to criticality", suggesting that the coexistence of scale-specific (neural oscillations) and scale-free (neuronal avalanches) dynamics in brain activity occurs close to a non-equilibrium critical point at the onset of self-sustained oscillations.}, author = {Lombardi, Fabrizio and Pepic, Selver and Shriki, Oren and Tkačik, Gašper and De Martino, Daniele}, publisher = {arXiv}, title = {{Quantifying the coexistence of neuronal oscillations and avalanches}}, doi = {10.48550/ARXIV.2108.06686}, year = {2021}, } @unpublished{10080, abstract = {Hippocampal and neocortical neural activity is modulated by the position of the individual in space. While hippocampal neurons provide the basis for a spatial map, prefrontal cortical neurons generalize over environmental features. Whether these generalized representations result from a bidirectional interaction with, or are mainly derived from hippocampal spatial representations is not known. By examining simultaneously recorded hippocampal and medial prefrontal neurons, we observed that prefrontal spatial representations show a delayed coherence with hippocampal ones. We also identified subpopulations of cells in the hippocampus and medial prefrontal cortex that formed functional cross-area couplings; these resembled the optimal connections predicted by a probabilistic model of spatial information transfer and generalization. Moreover, cross-area couplings were strongest and had the shortest delay preceding spatial decision-making. Our results suggest that generalized spatial coding in the medial prefrontal cortex is inherited from spatial representations in the hippocampus, and that the routing of information can change dynamically with behavioral demands.}, author = {Nardin, Michele and Käfer, Karola and Csicsvari, Jozsef L}, booktitle = {bioRxiv}, title = {{The generalized spatial representation in the prefrontal cortex is inherited from the hippocampus}}, doi = {10.1101/2021.09.30.462269}, year = {2021}, } @article{9905, abstract = {Vaccines are thought to be the best available solution for controlling the ongoing SARS-CoV-2 pandemic. However, the emergence of vaccine-resistant strains may come too rapidly for current vaccine developments to alleviate the health, economic and social consequences of the pandemic. To quantify and characterize the risk of such a scenario, we created a SIR-derived model with initial stochastic dynamics of the vaccine-resistant strain to study the probability of its emergence and establishment. Using parameters realistically resembling SARS-CoV-2 transmission, we model a wave-like pattern of the pandemic and consider the impact of the rate of vaccination and the strength of non-pharmaceutical intervention measures on the probability of emergence of a resistant strain. As expected, we found that a fast rate of vaccination decreases the probability of emergence of a resistant strain. Counterintuitively, when a relaxation of non-pharmaceutical interventions happened at a time when most individuals of the population have already been vaccinated the probability of emergence of a resistant strain was greatly increased. Consequently, we show that a period of transmission reduction close to the end of the vaccination campaign can substantially reduce the probability of resistant strain establishment. Our results suggest that policymakers and individuals should consider maintaining non-pharmaceutical interventions and transmission-reducing behaviours throughout the entire vaccination period.}, author = {Rella, Simon and Kulikova, Yuliya A. and Dermitzakis, Emmanouil T. and Kondrashov, Fyodor}, issn = {2045-2322}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, title = {{Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains}}, doi = {10.1038/s41598-021-95025-3}, volume = {11}, year = {2021}, } @phdthesis{9418, abstract = {Deep learning is best known for its empirical success across a wide range of applications spanning computer vision, natural language processing and speech. Of equal significance, though perhaps less known, are its ramifications for learning theory: deep networks have been observed to perform surprisingly well in the high-capacity regime, aka the overfitting or underspecified regime. Classically, this regime on the far right of the bias-variance curve is associated with poor generalisation; however, recent experiments with deep networks challenge this view. This thesis is devoted to investigating various aspects of underspecification in deep learning. First, we argue that deep learning models are underspecified on two levels: a) any given training dataset can be fit by many different functions, and b) any given function can be expressed by many different parameter configurations. We refer to the second kind of underspecification as parameterisation redundancy and we precisely characterise its extent. Second, we characterise the implicit criteria (the inductive bias) that guide learning in the underspecified regime. Specifically, we consider a nonlinear but tractable classification setting, and show that given the choice, neural networks learn classifiers with a large margin. Third, we consider learning scenarios where the inductive bias is not by itself sufficient to deal with underspecification. We then study different ways of ‘tightening the specification’: i) In the setting of representation learning with variational autoencoders, we propose a hand- crafted regulariser based on mutual information. ii) In the setting of binary classification, we consider soft-label (real-valued) supervision. We derive a generalisation bound for linear networks supervised in this way and verify that soft labels facilitate fast learning. Finally, we explore an application of soft-label supervision to the training of multi-exit models.}, author = {Bui Thi Mai, Phuong}, issn = {2663-337X}, pages = {125}, publisher = {Institute of Science and Technology Austria}, title = {{Underspecification in deep learning}}, doi = {10.15479/AT:ISTA:9418}, year = {2021}, } @inproceedings{9416, abstract = {We study the inductive bias of two-layer ReLU networks trained by gradient flow. We identify a class of easy-to-learn (`orthogonally separable') datasets, and characterise the solution that ReLU networks trained on such datasets converge to. Irrespective of network width, the solution turns out to be a combination of two max-margin classifiers: one corresponding to the positive data subset and one corresponding to the negative data subset. The proof is based on the recently introduced concept of extremal sectors, for which we prove a number of properties in the context of orthogonal separability. In particular, we prove stationarity of activation patterns from some time onwards, which enables a reduction of the ReLU network to an ensemble of linear subnetworks.}, author = {Bui Thi Mai, Phuong and Lampert, Christoph}, booktitle = {9th International Conference on Learning Representations}, location = {Virtual}, title = {{The inductive bias of ReLU networks on orthogonally separable data}}, year = {2021}, } @unpublished{10579, abstract = {We consider a totally asymmetric simple exclusion process (TASEP) consisting of particles on a lattice that require binding by a "token" to move. Using a combination of theory and simulations, we address the following questions: (i) How token binding kinetics affects the current-density relation; (ii) How the current-density relation depends on the scarcity of tokens; (iii) How tokens propagate the effects of the locally-imposed disorder (such a slow site) over the entire lattice; (iv) How a shared pool of tokens couples concurrent TASEPs running on multiple lattices; (v) How our results translate to TASEPs with open boundaries that exchange particles with the reservoir. Since real particle motion (including in systems that inspired the standard TASEP model, e.g., protein synthesis or movement of molecular motors) is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven TASEP dynamics analyzed in this paper should allow for a better understanding of real systems and enable a closer match between TASEP theory and experimental observations.}, author = {Kavcic, Bor and Tkačik, Gašper}, booktitle = {arXiv}, title = {{Token-driven totally asymmetric simple exclusion process}}, doi = {10.48550/arXiv.2112.13558}, year = {2021}, } @article{15279, abstract = {We formulate and prove an analog of Poonen’s finite-field Bertini theorem with Taylor conditions that holds in the Grothendieck ring of varieties. This gives a broad generalization of the work of Vakil and Wood, who treated the case of smooth hypersurface sections, and is made possible by the use of motivic Euler products to write down candidate motivic probabilities. As applications, we give motivic analogs of many results in arithmetic statistics that have been proven using Poonen’s sieve, including work of Bucur and Kedlaya on complete intersections and Erman and Wood on semiample Bertini theorems.}, author = {Bilu, Margaret and Howe, Sean}, issn = {1944-7833}, journal = {Algebra & Number Theory}, keywords = {Algebra and Number Theory}, number = {9}, pages = {2195--2259}, publisher = {Mathematical Sciences Publishers}, title = {{Motivic Euler products in motivic statistics}}, doi = {10.2140/ant.2021.15.2195}, volume = {15}, year = {2021}, } @unpublished{12076, abstract = {We find an asymptotic formula for the number of primitive vectors $(z_1,\ldots,z_4)\in (\mathbb{Z}_{\neq 0})^4$ such that $z_1,\ldots, z_4$ are all squareful and bounded by $B$, and $z_1+\cdots + z_4 = 0$. Our result agrees in the power of $B$ and $\log B$ with the Campana-Manin conjecture of Pieropan, Smeets, Tanimoto and V\'{a}rilly-Alvarado.}, author = {Shute, Alec L}, booktitle = {arXiv}, title = {{Sums of four squareful numbers}}, doi = {10.48550/arXiv.2104.06966}, year = {2021}, } @article{9260, abstract = {We study the density of rational points on a higher-dimensional orbifold (Pn−1,Δ) when Δ is a Q-divisor involving hyperplanes. This allows us to address a question of Tanimoto about whether the set of rational points on such an orbifold constitutes a thin set. Our approach relies on the Hardy–Littlewood circle method to first study an asymptotic version of Waring’s problem for mixed powers. In doing so we make crucial use of the recent resolution of the main conjecture in Vinogradov’s mean value theorem, due to Bourgain–Demeter–Guth and Wooley.}, author = {Browning, Timothy D and Yamagishi, Shuntaro}, issn = {1432-1823}, journal = {Mathematische Zeitschrift}, pages = {1071–1101}, publisher = {Springer Nature}, title = {{Arithmetic of higher-dimensional orbifolds and a mixed Waring problem}}, doi = {10.1007/s00209-021-02695-w}, volume = {299}, year = {2021}, } @article{10711, abstract = {In this paper, we investigate the distribution of the maximum of partial sums of families of m -periodic complex-valued functions satisfying certain conditions. We obtain precise uniform estimates for the distribution function of this maximum in a near-optimal range. Our results apply to partial sums of Kloosterman sums and other families of ℓ -adic trace functions, and are as strong as those obtained by Bober, Goldmakher, Granville and Koukoulopoulos for character sums. In particular, we improve on the recent work of the third author for Birch sums. However, unlike character sums, we are able to construct families of m -periodic complex-valued functions which satisfy our conditions, but for which the Pólya–Vinogradov inequality is sharp.}, author = {Autissier, Pascal and Bonolis, Dante and Lamzouri, Youness}, issn = {1570-5846}, journal = {Compositio Mathematica}, keywords = {Algebra and Number Theory}, number = {7}, pages = {1610--1651}, publisher = {Cambridge University Press}, title = {{The distribution of the maximum of partial sums of Kloosterman sums and other trace functions}}, doi = {10.1112/s0010437x21007351}, volume = {157}, year = {2021}, } @inproceedings{10325, abstract = {Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains.}, author = {Zamyatin, Alexei and Al-Bassam, Mustafa and Zindros, Dionysis and Kokoris Kogias, Eleftherios and Moreno-Sanchez, Pedro and Kiayias, Aggelos and Knottenbelt, William J.}, booktitle = {25th International Conference on Financial Cryptography and Data Security}, isbn = {9-783-6626-4330-3}, issn = {1611-3349}, location = {Virtual}, pages = {3--36}, publisher = {Springer Nature}, title = {{SoK: Communication across distributed ledgers}}, doi = {10.1007/978-3-662-64331-0_1}, volume = {12675 }, year = {2021}, } @inproceedings{10599, abstract = {A two-part successive syndrome-check decoding of polar codes is proposed with the first part successively refining the received codeword and the second part checking its syndrome. A new formulation of the successive-cancellation (SC) decoding algorithm is presented that allows for successively refining the received codeword by comparing the log-likelihood ratio value of a frozen bit with its predefined value. The syndrome of the refined received codeword is then checked for possible errors. In case there are no errors, the decoding process is terminated. Otherwise, the decoder continues to refine the received codeword. The proposed method is extended to the case of SC list (SCL) decoding by terminating the decoding process when the syndrome of the best candidate in the list indicates no errors. Simulation results show that the proposed method reduces the time-complexity of SC and SCL decoders and their fast variants, especially at high signal-to-noise ratios.}, author = {Hashemi, Seyyed Ali and Mondelli, Marco and Cioffi, John and Goldsmith, Andrea}, booktitle = {Proceedings of the 55th Asilomar Conference on Signals, Systems, and Computers}, isbn = {9781665458283}, issn = {1058-6393}, location = {Virtual, Pacific Grove, CA, United States}, pages = {943--947}, publisher = {IEEE}, title = {{Successive syndrome-check decoding of polar codes}}, doi = {10.1109/IEEECONF53345.2021.9723394}, volume = {2021-October}, year = {2021}, } @inproceedings{10597, abstract = {We thank Emmanuel Abbe and Min Ye for providing us the implementation of RPA decoding. D. Fathollahi and M. Mondelli are partially supported by the 2019 Lopez-Loreta Prize. N. Farsad is supported by Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Canada Foundation for Innovation (CFI), John R. Evans Leader Fund. S. A. Hashemi is supported by a Postdoctoral Fellowship from NSERC.}, author = {Fathollahi, Dorsa and Farsad, Nariman and Hashemi, Seyyed Ali and Mondelli, Marco}, booktitle = {2021 IEEE International Symposium on Information Theory}, isbn = {978-1-5386-8210-4}, location = {Virtual, Melbourne, Australia}, pages = {1082--1087}, publisher = {IEEE}, title = {{Sparse multi-decoder recursive projection aggregation for Reed-Muller codes}}, doi = {10.1109/isit45174.2021.9517887}, year = {2021}, } @inproceedings{10002, abstract = {We present a faster symbolic algorithm for the following central problem in probabilistic verification: Compute the maximal end-component (MEC) decomposition of Markov decision processes (MDPs). This problem generalizes the SCC decomposition problem of graphs and closed recurrent sets of Markov chains. The model of symbolic algorithms is widely used in formal verification and model-checking, where access to the input model is restricted to only symbolic operations (e.g., basic set operations and computation of one-step neighborhood). For an input MDP with n vertices and m edges, the classical symbolic algorithm from the 1990s for the MEC decomposition requires O(n2) symbolic operations and O(1) symbolic space. The only other symbolic algorithm for the MEC decomposition requires O(nm−−√) symbolic operations and O(m−−√) symbolic space. A main open question is whether the worst-case O(n2) bound for symbolic operations can be beaten. We present a symbolic algorithm that requires O˜(n1.5) symbolic operations and O˜(n−−√) symbolic space. Moreover, the parametrization of our algorithm provides a trade-off between symbolic operations and symbolic space: for all 0<ϵ≤1/2 the symbolic algorithm requires O˜(n2−ϵ) symbolic operations and O˜(nϵ) symbolic space ( O˜ hides poly-logarithmic factors). Using our techniques we present faster algorithms for computing the almost-sure winning regions of ω -regular objectives for MDPs. We consider the canonical parity objectives for ω -regular objectives, and for parity objectives with d -priorities we present an algorithm that computes the almost-sure winning region with O˜(n2−ϵ) symbolic operations and O˜(nϵ) symbolic space, for all 0<ϵ≤1/2 .}, author = {Chatterjee, Krishnendu and Dvorak, Wolfgang and Henzinger, Monika H and Svozil, Alexander}, booktitle = {Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science}, isbn = {978-1-6654-4896-3}, issn = {1043-6871}, keywords = {Computer science, Computational modeling, Markov processes, Probabilistic logic, Formal verification, Game Theory}, location = {Rome, Italy}, pages = {1--13}, publisher = {IEEE}, title = {{Symbolic time and space tradeoffs for probabilistic verification}}, doi = {10.1109/LICS52264.2021.9470739}, year = {2021}, } @inproceedings{9356, abstract = {In runtime verification, a monitor watches a trace of a system and, if possible, decides after observing each finite prefix whether or not the unknown infinite trace satisfies a given specification. We generalize the theory of runtime verification to monitors that attempt to estimate numerical values of quantitative trace properties (instead of attempting to conclude boolean values of trace specifications), such as maximal or average response time along a trace. Quantitative monitors are approximate: with every finite prefix, they can improve their estimate of the infinite trace's unknown property value. Consequently, quantitative monitors can be compared with regard to a precision-cost trade-off: better approximations of the property value require more monitor resources, such as states (in the case of finite-state monitors) or registers, and additional resources yield better approximations. We introduce a formal framework for quantitative and approximate monitoring, show how it conservatively generalizes the classical boolean setting for monitoring, and give several precision-cost trade-offs for monitors. For example, we prove that there are quantitative properties for which every additional register improves monitoring precision.}, author = {Henzinger, Thomas A and Sarac, Naci E}, booktitle = {Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science}, location = {Online}, publisher = {IEEE}, title = {{Quantitative and approximate monitoring}}, doi = {10.1109/LICS52264.2021.9470547}, year = {2021}, } @inproceedings{10004, abstract = {Markov chains are the de facto finite-state model for stochastic dynamical systems, and Markov decision processes (MDPs) extend Markov chains by incorporating non-deterministic behaviors. Given an MDP and rewards on states, a classical optimization criterion is the maximal expected total reward where the MDP stops after T steps, which can be computed by a simple dynamic programming algorithm. We consider a natural generalization of the problem where the stopping times can be chosen according to a probability distribution, such that the expected stopping time is T, to optimize the expected total reward. Quite surprisingly we establish inter-reducibility of the expected stopping-time problem for Markov chains with the Positivity problem (which is related to the well-known Skolem problem), for which establishing either decidability or undecidability would be a major breakthrough. Given the hardness of the exact problem, we consider the approximate version of the problem: we show that it can be solved in exponential time for Markov chains and in exponential space for MDPs.}, author = {Chatterjee, Krishnendu and Doyen, Laurent}, booktitle = {Proceedings of the 36th Annual ACM/IEEE Symposium on Logic in Computer Science}, isbn = {978-1-6654-4896-3}, issn = {1043-6871}, keywords = {Computer science, Heuristic algorithms, Memory management, Automata, Markov processes, Probability distribution, Complexity theory}, location = {Rome, Italy}, pages = {1--13}, publisher = {IEEE}, title = {{Stochastic processes with expected stopping time}}, doi = {10.1109/LICS52264.2021.9470595}, year = {2021}, } @article{9828, abstract = {Amplitude demodulation is a classical operation used in signal processing. For a long time, its effective applications in practice have been limited to narrowband signals. In this work, we generalize amplitude demodulation to wideband signals. We pose demodulation as a recovery problem of an oversampled corrupted signal and introduce special iterative schemes belonging to the family of alternating projection algorithms to solve it. Sensibly chosen structural assumptions on the demodulation outputs allow us to reveal the high inferential accuracy of the method over a rich set of relevant signals. This new approach surpasses current state-of-the-art demodulation techniques apt to wideband signals in computational efficiency by up to many orders of magnitude with no sacrifice in quality. Such performance opens the door for applications of the amplitude demodulation procedure in new contexts. In particular, the new method makes online and large-scale offline data processing feasible, including the calculation of modulator-carrier pairs in higher dimensions and poor sampling conditions, independent of the signal bandwidth. We illustrate the utility and specifics of applications of the new method in practice by using natural speech and synthetic signals.}, author = {Gabrielaitis, Mantas}, issn = {1941-0476}, journal = {IEEE Transactions on Signal Processing}, pages = {4039 -- 4054}, publisher = {IEEE}, title = {{Fast and accurate amplitude demodulation of wideband signals}}, doi = {10.1109/TSP.2021.3087899}, volume = {69}, year = {2021}, }