@article{8225, abstract = {Birch pollen allergy is among the most prevalent pollen allergies in Northern and Central Europe. This IgE-mediated disease can be treated with allergen immunotherapy (AIT), which typically gives rise to IgG antibodies inducing tolerance. Although the main mechanisms of allergen immunotherapy (AIT) are known, questions regarding possible Fc-mediated effects of IgG antibodies remain unanswered. This can mainly be attributed to the unavailability of appropriate tools, i.e., well-characterised recombinant antibodies (rAbs). We hereby aimed at providing human rAbs of several classes for mechanistic studies and as possible candidates for passive immunotherapy. We engineered IgE, IgG1, and IgG4 sharing the same variable region against the major birch pollen allergen Bet v 1 using Polymerase Incomplete Primer Extension (PIPE) cloning. We tested IgE functionality and IgG blocking capabilities using appropriate model cell lines. In vitro studies showed IgE engagement with FcεRI and CD23 and Bet v 1-dependent degranulation. Overall, we hereby present fully functional, human IgE, IgG1, and IgG4 sharing the same variable region against Bet v 1 and showcase possible applications in first mechanistic studies. Furthermore, our IgG antibodies might be useful candidates for passive immunotherapy of birch pollen allergy.}, author = {Köhler, Verena K. and Crescioli, Silvia and Fazekas-Singer, Judit and Bax, Heather J. and Hofer, Gerhard and Pranger, Christina L. and Hufnagl, Karin and Bianchini, Rodolfo and Flicker, Sabine and Keller, Walter and Karagiannis, Sophia N. and Jensen-Jarolim, Erika}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, number = {16}, publisher = {MDPI}, title = {{Filling the antibody pipeline in allergy: PIPE cloning of IgE, IgG1 and IgG4 against the major birch pollen allergen Bet v 1}}, doi = {10.3390/ijms21165693}, volume = {21}, year = {2020}, } @article{8226, author = {Gotovina, Jelena and Bianchini, Rodolfo and Fazekas-Singer, Judit and Herrmann, Ina and Pellizzari, Giulia and Haidl, Ian D. and Hufnagl, Karin and Karagiannis, Sophia N. and Marshall, Jean S. and Jensen‐Jarolim, Erika}, issn = {0105-4538}, journal = {Allergy}, publisher = {Wiley}, title = {{Epinephrine drives human M2a allergic macrophages to a regulatory phenotype reducing mast cell degranulation in vitro}}, doi = {10.1111/all.14299}, year = {2020}, } @article{8250, abstract = {Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Mechanisms of drug interactions between translation-inhibiting antibiotics}}, doi = {10.1038/s41467-020-17734-z}, volume = {11}, year = {2020}, } @misc{8254, abstract = {Here are the research data underlying the publication "Estimating inbreeding and its effects in a long-term study of snapdragons (Antirrhinum majus)". Further information are summed up in the README document. The files for this record have been updated and are now found in the linked DOI https://doi.org/10.15479/AT:ISTA:9192.}, author = {Arathoon, Louise S}, publisher = {Institute of Science and Technology Austria}, title = {{Estimating inbreeding and its effects in a long-term study of snapdragons (Antirrhinum majus)}}, doi = {10.15479/AT:ISTA:8254}, year = {2020}, } @article{8261, abstract = {Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.}, author = {Zhang, Xiaomin and Schlögl, Alois and Jonas, Peter M}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1212--1225}, publisher = {Elsevier}, title = {{Selective routing of spatial information flow from input to output in hippocampal granule cells}}, doi = {10.1016/j.neuron.2020.07.006}, volume = {107}, year = {2020}, } @article{8268, abstract = {Modern scientific instruments produce vast amounts of data, which can overwhelm the processing ability of computer systems. Lossy compression of data is an intriguing solution, but comes with its own drawbacks, such as potential signal loss, and the need for careful optimization of the compression ratio. In this work, we focus on a setting where this problem is especially acute: compressive sensing frameworks for interferometry and medical imaging. We ask the following question: can the precision of the data representation be lowered for all inputs, with recovery guarantees and practical performance Our first contribution is a theoretical analysis of the normalized Iterative Hard Thresholding (IHT) algorithm when all input data, meaning both the measurement matrix and the observation vector are quantized aggressively. We present a variant of low precision normalized IHT that, under mild conditions, can still provide recovery guarantees. The second contribution is the application of our quantization framework to radio astronomy and magnetic resonance imaging. We show that lowering the precision of the data can significantly accelerate image recovery. We evaluate our approach on telescope data and samples of brain images using CPU and FPGA implementations achieving up to a 9x speedup with negligible loss of recovery quality.}, author = {Gurel, Nezihe Merve and Kara, Kaan and Stojanov, Alen and Smith, Tyler and Lemmin, Thomas and Alistarh, Dan-Adrian and Puschel, Markus and Zhang, Ce}, issn = {19410476}, journal = {IEEE Transactions on Signal Processing}, pages = {4268--4282}, publisher = {IEEE}, title = {{Compressive sensing using iterative hard thresholding with low precision data representation: Theory and applications}}, doi = {10.1109/TSP.2020.3010355}, volume = {68}, year = {2020}, } @article{8271, author = {He, Peng and Zhang, Yuzhou and Xiao, Guanghui}, issn = {17529867}, journal = {Molecular Plant}, number = {9}, pages = {1238--1240}, publisher = {Elsevier}, title = {{Origin of a subgenome and genome evolution of allotetraploid cotton species}}, doi = {10.1016/j.molp.2020.07.006}, volume = {13}, year = {2020}, } @inproceedings{8272, abstract = {We study turn-based stochastic zero-sum games with lexicographic preferences over reachability and safety objectives. Stochastic games are standard models in control, verification, and synthesis of stochastic reactive systems that exhibit both randomness as well as angelic and demonic non-determinism. Lexicographic order allows to consider multiple objectives with a strict preference order over the satisfaction of the objectives. To the best of our knowledge, stochastic games with lexicographic objectives have not been studied before. We establish determinacy of such games and present strategy and computational complexity results. For strategy complexity, we show that lexicographically optimal strategies exist that are deterministic and memory is only required to remember the already satisfied and violated objectives. For a constant number of objectives, we show that the relevant decision problem is in NP∩coNP , matching the current known bound for single objectives; and in general the decision problem is PSPACE -hard and can be solved in NEXPTIME∩coNEXPTIME . We present an algorithm that computes the lexicographically optimal strategies via a reduction to computation of optimal strategies in a sequence of single-objectives games. We have implemented our algorithm and report experimental results on various case studies.}, author = {Chatterjee, Krishnendu and Katoen, Joost P and Weininger, Maximilian and Winkler, Tobias}, booktitle = {International Conference on Computer Aided Verification}, isbn = {9783030532901}, issn = {16113349}, pages = {398--420}, publisher = {Springer Nature}, title = {{Stochastic games with lexicographic reachability-safety objectives}}, doi = {10.1007/978-3-030-53291-8_21}, volume = {12225}, year = {2020}, } @article{8283, abstract = {Drought and salt stress are the main environmental cues affecting the survival, development, distribution, and yield of crops worldwide. MYB transcription factors play a crucial role in plants’ biological processes, but the function of pineapple MYB genes is still obscure. In this study, one of the pineapple MYB transcription factors, AcoMYB4, was isolated and characterized. The results showed that AcoMYB4 is localized in the cell nucleus, and its expression is induced by low temperature, drought, salt stress, and hormonal stimulation, especially by abscisic acid (ABA). Overexpression of AcoMYB4 in rice and Arabidopsis enhanced plant sensitivity to osmotic stress; it led to an increase in the number stomata on leaf surfaces and lower germination rate under salt and drought stress. Furthermore, in AcoMYB4 OE lines, the membrane oxidation index, free proline, and soluble sugar contents were decreased. In contrast, electrolyte leakage and malondialdehyde (MDA) content increased significantly due to membrane injury, indicating higher sensitivity to drought and salinity stresses. Besides the above, both the expression level and activities of several antioxidant enzymes were decreased, indicating lower antioxidant activity in AcoMYB4 transgenic plants. Moreover, under osmotic stress, overexpression of AcoMYB4 inhibited ABA biosynthesis through a decrease in the transcription of genes responsible for ABA synthesis (ABA1 and ABA2) and ABA signal transduction factor ABI5. These results suggest that AcoMYB4 negatively regulates osmotic stress by attenuating cellular ABA biosynthesis and signal transduction pathways. }, author = {Chen, Huihuang and Lai, Linyi and Li, Lanxin and Liu, Liping and Jakada, Bello Hassan and Huang, Youmei and He, Qing and Chai, Mengnan and Niu, Xiaoping and Qin, Yuan}, issn = {14220067}, journal = {International Journal of Molecular Sciences}, number = {16}, publisher = {MDPI}, title = {{AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling}}, doi = {10.3390/ijms21165727}, volume = {21}, year = {2020}, } @article{8284, abstract = {Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements.}, author = {Steiner, Julia and Sazanov, Leonid A}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter}}, doi = {10.7554/eLife.59407}, volume = {9}, year = {2020}, } @article{8285, abstract = {We demonstrate the utility of optical cavity generated spin-squeezed states in free space atomic fountain clocks in ensembles of 390 000 87Rb atoms. Fluorescence imaging, correlated to an initial quantum nondemolition measurement, is used for population spectroscopy after the atoms are released from a confining lattice. For a free fall time of 4 milliseconds, we resolve a single-shot phase sensitivity of 814(61) microradians, which is 5.8(0.6) decibels (dB) below the quantum projection limit. We observe that this squeezing is preserved as the cloud expands to a roughly 200  μm radius and falls roughly 300  μm in free space. Ramsey spectroscopy with 240 000 atoms at a 3.6 ms Ramsey time results in a single-shot fractional frequency stability of 8.4(0.2)×10−12, 3.8(0.2) dB below the quantum projection limit. The sensitivity and stability are limited by the technical noise in the fluorescence detection protocol and the microwave system, respectively.}, author = {Malia, Benjamin K. and Martínez-Rincón, Julián and Wu, Yunfan and Hosten, Onur and Kasevich, Mark A.}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {4}, publisher = {American Physical Society}, title = {{Free space Ramsey spectroscopy in rubidium with noise below the quantum projection limit}}, doi = {10.1103/PhysRevLett.125.043202}, volume = {125}, year = {2020}, } @inproceedings{8287, abstract = {Reachability analysis aims at identifying states reachable by a system within a given time horizon. This task is known to be computationally expensive for linear hybrid systems. Reachability analysis works by iteratively applying continuous and discrete post operators to compute states reachable according to continuous and discrete dynamics, respectively. In this paper, we enhance both of these operators and make sure that most of the involved computations are performed in low-dimensional state space. In particular, we improve the continuous-post operator by performing computations in high-dimensional state space only for time intervals relevant for the subsequent application of the discrete-post operator. Furthermore, the new discrete-post operator performs low-dimensional computations by leveraging the structure of the guard and assignment of a considered transition. We illustrate the potential of our approach on a number of challenging benchmarks.}, author = {Bogomolov, Sergiy and Forets, Marcelo and Frehse, Goran and Potomkin, Kostiantyn and Schilling, Christian}, booktitle = {Proceedings of the International Conference on Embedded Software}, keywords = {reachability, hybrid systems, decomposition}, location = {Virtual }, title = {{Reachability analysis of linear hybrid systems via block decomposition}}, year = {2020}, } @misc{8294, abstract = {Automated root growth analysis and tracking of root tips. }, author = {Hauschild, Robert}, publisher = {IST Austria}, title = {{RGtracker}}, doi = {10.15479/AT:ISTA:8294}, year = {2020}, } @unpublished{8307, abstract = {Classic Byzantine fault-tolerant consensus protocols forfeit liveness in the face of asynchrony in order to preserve safety, whereas most deployed blockchain protocols forfeit safety in order to remain live. In this work, we achieve the best of both worlds by proposing a novel abstractions called the finality gadget. A finality gadget allows for transactions to always optimistically commit but informs the clients that these transactions might be unsafe. As a result, a blockchain can execute transactions optimistically and only commit them after they have been sufficiently and provably audited. In this work, we formally model the finality gadget abstraction, prove that it is impossible to solve it deterministically in full asynchrony (even though it is stronger than consensus) and provide a partially synchronous protocol which is currently securing a major blockchain. This way we show that the protocol designer can decouple safety and liveness in order to speed up recovery from failures. We believe that there can be other types of finality gadgets that provide weaker safety (e.g., probabilistic) in order to gain more efficiency and this can depend on the probability that the network is not in synchrony.}, author = {Stewart, Alistair and Kokoris Kogias, Eleftherios}, booktitle = {arXiv}, title = {{GRANDPA: A Byzantine finality gadget}}, year = {2020}, } @article{8308, abstract = {Many-body localization provides a mechanism to avoid thermalization in isolated interacting quantum systems. The breakdown of thermalization may be complete, when all eigenstates in the many-body spectrum become localized, or partial, when the so-called many-body mobility edge separates localized and delocalized parts of the spectrum. Previously, De Roeck et al. [Phys. Rev. B 93, 014203 (2016)] suggested a possible instability of the many-body mobility edge in energy density. The local ergodic regions—so-called “bubbles”—resonantly spread throughout the system, leading to delocalization. In order to study such instability mechanism, in this work we design a model featuring many-body mobility edge in particle density: the states at small particle density are localized, while increasing the density of particles leads to delocalization. Using numerical simulations with matrix product states, we demonstrate the stability of many-body localization with respect to small bubbles in large dilute systems for experimentally relevant timescales. In addition, we demonstrate that processes where the bubble spreads are favored over processes that lead to resonant tunneling, suggesting a possible mechanism behind the observed stability of many-body mobility edge. We conclude by proposing experiments to probe particle density mobility edge in the Bose-Hubbard model.}, author = {Brighi, Pietro and Abanin, Dmitry A. and Serbyn, Maksym}, issn = {2469-9969}, journal = {Physical Review B}, number = {6}, publisher = {American Physical Society}, title = {{Stability of mobility edges in disordered interacting systems}}, doi = {10.1103/physrevb.102.060202}, volume = {102}, year = {2020}, } @article{8318, abstract = {Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.}, author = {Gutierrez-Fernandez, Javier and Kaszuba, Karol and Minhas, Gurdeep S. and Baradaran, Rozbeh and Tambalo, Margherita and Gallagher, David T. and Sazanov, Leonid A}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Key role of quinone in the mechanism of respiratory complex I}}, doi = {10.1038/s41467-020-17957-0}, volume = {11}, year = {2020}, } @article{8319, abstract = {We demonstrate that releasing atoms into free space from an optical lattice does not deteriorate cavity-generated spin squeezing for metrological purposes. In this work, an ensemble of 500000 spin-squeezed atoms in a high-finesse optical cavity with near-uniform atom-cavity coupling is prepared, released into free space, recaptured in the cavity, and probed. Up to ∼10 dB of metrologically relevant squeezing is retrieved for 700μs free-fall times, and decaying levels of squeezing are realized for up to 3 ms free-fall times. The degradation of squeezing results from loss of atom-cavity coupling homogeneity between the initial squeezed state generation and final collective state readout. A theoretical model is developed to quantify this degradation and this model is experimentally validated.}, author = {Wu, Yunfan and Krishnakumar, Rajiv and Martínez-Rincón, Julián and Malia, Benjamin K. and Hosten, Onur and Kasevich, Mark A.}, issn = {24699934}, journal = {Physical Review A}, number = {1}, publisher = {American Physical Society}, title = {{Retrieval of cavity-generated atomic spin squeezing after free-space release}}, doi = {10.1103/PhysRevA.102.012224}, volume = {102}, year = {2020}, } @article{8320, abstract = {The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications.}, author = {Mukba, S. A. and Vlasov, Petr and Kolosov, P. M. and Shuvalova, E. Y. and Egorova, T. V. and Alkalaeva, E. Z.}, issn = {16083245}, journal = {Molecular Biology}, number = {4}, pages = {475--484}, publisher = {Springer Nature}, title = {{Expanding the genetic code: Unnatural base pairs in biological systems}}, doi = {10.1134/S0026893320040111}, volume = {54}, year = {2020}, } @article{8321, abstract = {The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications.}, author = {Mukba, S. A. and Vlasov, Petr and Kolosov, P. M. and Shuvalova, E. Y. and Egorova, T. V. and Alkalaeva, E. Z.}, issn = {00268984}, journal = {Molekuliarnaia biologiia}, number = {4}, pages = {531--541}, publisher = {Russian Academy of Sciences}, title = {{Expanding the genetic code: Unnatural base pairs in biological systems}}, doi = {10.31857/S0026898420040126}, volume = {54}, year = {2020}, } @inproceedings{8322, abstract = {Reverse firewalls were introduced at Eurocrypt 2015 by Miro-nov and Stephens-Davidowitz, as a method for protecting cryptographic protocols against attacks on the devices of the honest parties. In a nutshell: a reverse firewall is placed outside of a device and its goal is to “sanitize” the messages sent by it, in such a way that a malicious device cannot leak its secrets to the outside world. It is typically assumed that the cryptographic devices are attacked in a “functionality-preserving way” (i.e. informally speaking, the functionality of the protocol remains unchanged under this attacks). In their paper, Mironov and Stephens-Davidowitz construct a protocol for passively-secure two-party computations with firewalls, leaving extension of this result to stronger models as an open question. In this paper, we address this problem by constructing a protocol for secure computation with firewalls that has two main advantages over the original protocol from Eurocrypt 2015. Firstly, it is a multiparty computation protocol (i.e. it works for an arbitrary number n of the parties, and not just for 2). Secondly, it is secure in much stronger corruption settings, namely in the active corruption model. More precisely: we consider an adversary that can fully corrupt up to 𝑛−1 parties, while the remaining parties are corrupt in a functionality-preserving way. Our core techniques are: malleable commitments and malleable non-interactive zero-knowledge, which in particular allow us to create a novel protocol for multiparty augmented coin-tossing into the well with reverse firewalls (that is based on a protocol of Lindell from Crypto 2001).}, author = {Chakraborty, Suvradip and Dziembowski, Stefan and Nielsen, Jesper Buus}, booktitle = {Advances in Cryptology – CRYPTO 2020}, isbn = {9783030568795}, issn = {16113349}, location = {Santa Barbara, CA, United States}, pages = {732--762}, publisher = {Springer Nature}, title = {{Reverse firewalls for actively secure MPCs}}, doi = {10.1007/978-3-030-56880-1_26}, volume = {12171}, year = {2020}, }