@misc{8313, abstract = {The present invention concerns a computer-implemented method for secure data exchange between a sender (A) and a recipient (B), wherein the method is performed by the sender (A) and comprises encrypting data using a symmetric key k, creating a write transaction T W , wherein the write transaction T W comprises information usable to derive the symmetric key k and an access policy identifying the recipient (B) as being allowed to decrypt the encrypted data, providing the recipient (B) access to the encrypted data, and sending the write transaction T W to a first group of servers (AC) for being stored in a blockchain data structure maintained by the first group of servers (AC).}, author = {Ford, Bryan and Gasser, Linus and Kokoris Kogias, Eleftherios and Janovic, Philipp}, title = {{Methods and systems for secure data exchange}}, year = {2019}, } @unpublished{8314, abstract = {Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called Wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee's approval for the last valid state. Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. Furthermore, we consider permissioned blockchains, where the additional property of auditability might be desired for regulatory purposes. We introduce Brick+, an off-chain construction that provides auditability on top of Brick without conflicting with its privacy guarantees. We formally define the properties our payment channel construction should fulfill, and prove that both Brick and Brick+ satisfy them. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity.}, author = {Avarikioti, Georgia and Kokoris Kogias, Eleftherios and Wattenhofer, Roger and Zindros, Dionysis}, booktitle = {arXiv}, title = {{Brick: Asynchronous payment channels}}, doi = {10.48550/arXiv.1905.11360}, year = {2019}, } @unpublished{8315, abstract = {Sharding distributed ledgers is the most promising on-chain solution for scaling blockchain technology. In this work, we define and analyze the properties a sharded distributed ledger should fulfill. More specifically, we show that a sharded blockchain cannot be scalable under a fully adaptive adversary, but it can scale up to $O(n/\log n)$ under an epoch-adaptive adversary. This is possible only if the distributed ledger creates succinct proofs of the valid state updates at the end of each epoch. Our model builds upon and extends the Bitcoin backbone protocol by defining consistency and scalability. Consistency encompasses the need for atomic execution of cross-shard transactions to preserve safety, whereas scalability encapsulates the speedup a sharded system can gain in comparison to a non-sharded system. In order to show the power of our framework, we analyze the most prominent sharded blockchains and either prove their correctness (OmniLedger, RapidChain) under our model or pinpoint where they fail to balance the consistency and scalability requirements (Elastico, Monoxide). }, author = {Avarikioti, Georgia and Kokoris Kogias, Eleftherios and Wattenhofer, Roger}, booktitle = {arXiv}, title = {{Divide and scale: Formalization of distributed ledger sharding protocols}}, doi = {10.48550/arXiv.1910.10434}, year = {2019}, } @article{8405, abstract = {Atomic-resolution structure determination is crucial for understanding protein function. Cryo-EM and NMR spectroscopy both provide structural information, but currently cryo-EM does not routinely give access to atomic-level structural data, and, generally, NMR structure determination is restricted to small (<30 kDa) proteins. We introduce an integrated structure determination approach that simultaneously uses NMR and EM data to overcome the limits of each of these methods. The approach enables structure determination of the 468 kDa large dodecameric aminopeptidase TET2 to a precision and accuracy below 1 Å by combining secondary-structure information obtained from near-complete magic-angle-spinning NMR assignments of the 39 kDa-large subunits, distance restraints from backbone amides and ILV methyl groups, and a 4.1 Å resolution EM map. The resulting structure exceeds current standards of NMR and EM structure determination in terms of molecular weight and precision. Importantly, the approach is successful even in cases where only medium-resolution cryo-EM data are available.}, author = {Gauto, Diego F. and Estrozi, Leandro F. and Schwieters, Charles D. and Effantin, Gregory and Macek, Pavel and Sounier, Remy and Sivertsen, Astrid C. and Schmidt, Elena and Kerfah, Rime and Mas, Guillaume and Colletier, Jacques-Philippe and Güntert, Peter and Favier, Adrien and Schoehn, Guy and Schanda, Paul and Boisbouvier, Jerome}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex}}, doi = {10.1038/s41467-019-10490-9}, volume = {10}, year = {2019}, } @article{8406, abstract = {Coordinated conformational transitions in oligomeric enzymatic complexes modulate function in response to substrates and play a crucial role in enzyme inhibition and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which has emerged as a drug target against multiple pathogenic bacteria. Activation of different ClpPs by inhibitors has been independently reported from drug development efforts, but no rationale for inhibitor-induced activation has been hitherto proposed. Using an integrated approach that includes x-ray crystallography, solid- and solution-state nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the proteasome inhibitor bortezomib binds to the ClpP active-site serine, mimicking a peptide substrate, and induces a concerted allosteric activation of the complex. The bortezomib-activated conformation also exhibits a higher affinity for its cognate unfoldase ClpX. We propose a universal allosteric mechanism, where substrate binding to a single subunit locks ClpP into an active conformation optimized for chaperone association and protein processive degradation.}, author = {Felix, Jan and Weinhäupl, Katharina and Chipot, Christophe and Dehez, François and Hessel, Audrey and Gauto, Diego F. and Morlot, Cecile and Abian, Olga and Gutsche, Irina and Velazquez-Campoy, Adrian and Schanda, Paul and Fraga, Hugo}, issn = {2375-2548}, journal = {Science Advances}, number = {9}, publisher = {American Association for the Advancement of Science}, title = {{Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors}}, doi = {10.1126/sciadv.aaw3818}, volume = {5}, year = {2019}, } @article{8407, author = {Schanda, Paul}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, keywords = {Nuclear and High Energy Physics, Biophysics, Biochemistry, Condensed Matter Physics}, pages = {180--186}, publisher = {Elsevier}, title = {{Relaxing with liquids and solids – A perspective on biomolecular dynamics}}, doi = {10.1016/j.jmr.2019.07.025}, volume = {306}, year = {2019}, } @article{8408, abstract = {Aromatic residues are located at structurally important sites of many proteins. Probing their interactions and dynamics can provide important functional insight but is challenging in large proteins. Here, we introduce approaches to characterize dynamics of phenylalanine residues using 1H-detected fast magic-angle spinning (MAS) NMR combined with a tailored isotope-labeling scheme. Our approach yields isolated two-spin systems that are ideally suited for artefact-free dynamics measurements, and allows probing motions effectively without molecular-weight limitations. The application to the TET2 enzyme assembly of ~0.5 MDa size, the currently largest protein assigned by MAS NMR, provides insights into motions occurring on a wide range of time scales (ps-ms). We quantitatively probe ring flip motions, and show the temperature dependence by MAS NMR measurements down to 100 K. Interestingly, favorable line widths are observed down to 100 K, with potential implications for DNP NMR. Furthermore, we report the first 13C R1ρ MAS NMR relaxation-dispersion measurements and detect structural excursions occurring on a microsecond time scale in the entry pore to the catalytic chamber and at a trimer interface that was proposed as exit pore. We show that the labeling scheme with deuteration at ca. 50 kHz MAS provides superior resolution compared to 100 kHz MAS experiments with protonated, uniformly 13C-labeled samples.}, author = {Gauto, Diego F. and Macek, Pavel and Barducci, Alessandro and Fraga, Hugo and Hessel, Audrey and Terauchi, Tsutomu and Gajan, David and Miyanoiri, Yohei and Boisbouvier, Jerome and Lichtenecker, Roman and Kainosho, Masatsune and Schanda, Paul}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {28}, pages = {11183--11195}, publisher = {American Chemical Society}, title = {{Aromatic ring dynamics, thermal activation, and transient conformations of a 468 kDa enzyme by specific 1H–13C labeling and fast magic-angle spinning NMR}}, doi = {10.1021/jacs.9b04219}, volume = {141}, year = {2019}, } @article{8409, abstract = {The bacterial cell wall is composed of the peptidoglycan (PG), a large polymer that maintains the integrity of the bacterial cell. Due to its multi-gigadalton size, heterogeneity, and dynamics, atomic-resolution studies are inherently complex. Solid-state NMR is an important technique to gain insight into its structure, dynamics and interactions. Here, we explore the possibilities to study the PG with ultra-fast (100 kHz) magic-angle spinning NMR. We demonstrate that highly resolved spectra can be obtained, and show strategies to obtain site-specific resonance assignments and distance information. We also explore the use of proton-proton correlation experiments, thus opening the way for NMR studies of intact cell walls without the need for isotope labeling.}, author = {Bougault, Catherine and Ayala, Isabel and Vollmer, Waldemar and Simorre, Jean-Pierre and Schanda, Paul}, issn = {1047-8477}, journal = {Journal of Structural Biology}, keywords = {Structural Biology}, number = {1}, pages = {66--72}, publisher = {Elsevier}, title = {{Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency}}, doi = {10.1016/j.jsb.2018.07.009}, volume = {206}, year = {2019}, } @article{8410, author = {Schanda, Paul and Chekmenev, Eduard Y.}, issn = {1439-4235}, journal = {ChemPhysChem}, number = {2}, pages = {177--177}, publisher = {Wiley}, title = {{NMR for Biological Systems}}, doi = {10.1002/cphc.201801100}, volume = {20}, year = {2019}, } @article{8411, abstract = {Studying protein dynamics on microsecond‐to‐millisecond (μs‐ms) time scales can provide important insight into protein function. In magic‐angle‐spinning (MAS) NMR, μs dynamics can be visualized by R1p rotating‐frame relaxation dispersion experiments in different regimes of radio‐frequency field strengths: at low RF field strength, isotropic‐chemical‐shift fluctuation leads to “Bloch‐McConnell‐type” relaxation dispersion, while when the RF field approaches rotary resonance conditions bond angle fluctuations manifest as increased R1p rate constants (“Near‐Rotary‐Resonance Relaxation Dispersion”, NERRD). Here we explore the joint analysis of both regimes to gain comprehensive insight into motion in terms of geometric amplitudes, chemical‐shift changes, populations and exchange kinetics. We use a numerical simulation procedure to illustrate these effects and the potential of extracting exchange parameters, and apply the methodology to the study of a previously described conformational exchange process in microcrystalline ubiquitin.}, author = {Marion, Dominique and Gauto, Diego F. and Ayala, Isabel and Giandoreggio-Barranco, Karine and Schanda, Paul}, issn = {1439-4235}, journal = {ChemPhysChem}, keywords = {Physical and Theoretical Chemistry, Atomic and Molecular Physics, and Optics}, number = {2}, pages = {276--284}, publisher = {Wiley}, title = {{Microsecond protein dynamics from combined Bloch-McConnell and Near-Rotary-Resonance R1p relaxation-dispersion MAS NMR}}, doi = {10.1002/cphc.201800935}, volume = {20}, year = {2019}, } @article{8412, abstract = {Microsecond to millisecond timescale backbone dynamics of the amyloid core residues in Y145Stop human prion protein (PrP) fibrils were investigated by using 15N rotating frame (R1ρ) relaxation dispersion solid‐state nuclear magnetic resonance spectroscopy over a wide range of spin‐lock fields. Numerical simulations enabled the experimental relaxation dispersion profiles for most of the fibril core residues to be modelled by using a two‐state exchange process with a common exchange rate of 1000 s−1, corresponding to protein backbone motion on the timescale of 1 ms, and an excited‐state population of 2 %. We also found that the relaxation dispersion profiles for several amino acids positioned near the edges of the most structured regions of the amyloid core were better modelled by assuming somewhat higher excited‐state populations (∼5–15 %) and faster exchange rate constants, corresponding to protein backbone motions on the timescale of ∼100–300 μs. The slow backbone dynamics of the core residues were evaluated in the context of the structural model of human Y145Stop PrP amyloid.}, author = {Shannon, Matthew D. and Theint, Theint and Mukhopadhyay, Dwaipayan and Surewicz, Krystyna and Surewicz, Witold K. and Marion, Dominique and Schanda, Paul and Jaroniec, Christopher P.}, issn = {1439-4235}, journal = {ChemPhysChem}, keywords = {Physical and Theoretical Chemistry, Atomic and Molecular Physics, and Optics}, number = {2}, pages = {311--317}, publisher = {Wiley}, title = {{Conformational dynamics in the core of human Y145Stop prion protein amyloid probed by relaxation dispersion NMR}}, doi = {10.1002/cphc.201800779}, volume = {20}, year = {2019}, } @article{8413, abstract = {NMR relaxation dispersion methods provide a holistic way to observe microsecond time-scale protein backbone motion both in solution and in the solid state. Different nuclei (1H and 15N) and different relaxation dispersion techniques (Bloch–McConnell and near-rotary-resonance) give complementary information about the amplitudes and time scales of the conformational dynamics and provide comprehensive insights into the mechanistic details of the structural rearrangements. In this paper, we exemplify the benefits of the combination of various solution- and solid-state relaxation dispersion methods on a microcrystalline protein (α-spectrin SH3 domain), for which we are able to identify and model the functionally relevant conformational rearrangements around the ligand recognition loop occurring on multiple microsecond time scales. The observed loop motions suggest that the SH3 domain exists in a binding-competent conformation in dynamic equilibrium with a sterically impaired ground-state conformation both in solution and in crystalline form. This inherent plasticity between the interconverting macrostates is compatible with a conformational-preselection model and provides new insights into the recognition mechanisms of SH3 domains.}, author = {Rovó, Petra and Smith, Colin A. and Gauto, Diego and de Groot, Bert L. and Schanda, Paul and Linser, Rasmus}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {2}, pages = {858--869}, publisher = {American Chemical Society}, title = {{Mechanistic insights into microsecond time-scale motion of solid proteins using complementary 15N and 1H relaxation dispersion techniques}}, doi = {10.1021/jacs.8b09258}, volume = {141}, year = {2019}, } @article{8415, abstract = {We consider billiards obtained by removing three strictly convex obstacles satisfying the non-eclipse condition on the plane. The restriction of the dynamics to the set of non-escaping orbits is conjugated to a subshift on three symbols that provides a natural labeling of all periodic orbits. We study the following inverse problem: does the Marked Length Spectrum (i.e., the set of lengths of periodic orbits together with their labeling), determine the geometry of the billiard table? We show that from the Marked Length Spectrum it is possible to recover the curvature at periodic points of period two, as well as the Lyapunov exponent of each periodic orbit.}, author = {Bálint, Péter and De Simoi, Jacopo and Kaloshin, Vadim and Leguil, Martin}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, number = {3}, pages = {1531--1575}, publisher = {Springer Nature}, title = {{Marked length spectrum, homoclinic orbits and the geometry of open dispersing billiards}}, doi = {10.1007/s00220-019-03448-x}, volume = {374}, year = {2019}, } @article{8416, abstract = {In this paper, we show that any smooth one-parameter deformations of a strictly convex integrable billiard table Ω0 preserving the integrability near the boundary have to be tangent to a finite dimensional space passing through Ω0.}, author = {Huang, Guan and Kaloshin, Vadim}, issn = {1609-4514}, journal = {Moscow Mathematical Journal}, number = {2}, pages = {307--327}, publisher = {American Mathematical Society}, title = {{On the finite dimensionality of integrable deformations of strictly convex integrable billiard tables}}, doi = {10.17323/1609-4514-2019-19-2-307-327}, volume = {19}, year = {2019}, } @article{8418, abstract = {For the Restricted Circular Planar 3 Body Problem, we show that there exists an open set U in phase space of fixed measure, where the set of initial points which lead to collision is O(μ120) dense as μ→0.}, author = {Guardia, Marcel and Kaloshin, Vadim and Zhang, Jianlu}, issn = {0003-9527}, journal = {Archive for Rational Mechanics and Analysis}, keywords = {Mechanical Engineering, Mathematics (miscellaneous), Analysis}, number = {2}, pages = {799--836}, publisher = {Springer Nature}, title = {{Asymptotic density of collision orbits in the Restricted Circular Planar 3 Body Problem}}, doi = {10.1007/s00205-019-01368-7}, volume = {233}, year = {2019}, } @article{8693, abstract = {We review V. I. Arnold’s 1963 celebrated paper [1] Proof of A. N. Kolmogorov’s Theorem on the Conservation of Conditionally Periodic Motions with a Small Variation in the Hamiltonian, and prove that, optimising Arnold’s scheme, one can get “sharp” asymptotic quantitative conditions (as ε → 0, ε being the strength of the perturbation). All constants involved are explicitly computed.}, author = {Chierchia, Luigi and Koudjinan, Edmond}, journal = {Regular and Chaotic Dynamics}, pages = {583–606}, publisher = {Springer}, title = {{V. I. Arnold’s “pointwise” KAM theorem}}, doi = {10.1134/S1560354719060017}, volume = {24}, year = {2019}, } @article{9016, abstract = {Inhibiting the histone H3–ASF1 (anti‐silencing function 1) protein–protein interaction (PPI) represents a potential approach for treating numerous cancers. As an α‐helix‐mediated PPI, constraining the key histone H3 helix (residues 118–135) is a strategy through which chemical probes might be elaborated to test this hypothesis. In this work, variant H3118–135 peptides bearing pentenylglycine residues at the i and i+4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that the potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy–entropy compensation occurs.}, author = {Bakail, May M and Rodriguez‐Marin, Silvia and Hegedüs, Zsófia and Perrin, Marie E. and Ochsenbein, Françoise and Wilson, Andrew J.}, issn = {1439-4227}, journal = {ChemBioChem}, number = {7}, pages = {891--895}, publisher = {Wiley}, title = {{Recognition of ASF1 by using hydrocarbon‐constrained peptides}}, doi = {10.1002/cbic.201800633}, volume = {20}, year = {2019}, } @article{9018, abstract = {Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.}, author = {Bakail, May M and Gaubert, Albane and Andreani, Jessica and Moal, Gwenaëlle and Pinna, Guillaume and Boyarchuk, Ekaterina and Gaillard, Marie-Cécile and Courbeyrette, Regis and Mann, Carl and Thuret, Jean-Yves and Guichard, Bérengère and Murciano, Brice and Richet, Nicolas and Poitou, Adeline and Frederic, Claire and Le Du, Marie-Hélène and Agez, Morgane and Roelants, Caroline and Gurard-Levin, Zachary A. and Almouzni, Geneviève and Cherradi, Nadia and Guerois, Raphael and Ochsenbein, Françoise}, issn = {2451-9456}, journal = {Cell Chemical Biology}, keywords = {Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery}, number = {11}, pages = {1573--1585.e10}, publisher = {Elsevier}, title = {{Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1}}, doi = {10.1016/j.chembiol.2019.09.002}, volume = {26}, year = {2019}, } @article{9060, abstract = {Molecular motors are essential to the living, generating fluctuations that boost transport and assist assembly. Active colloids, that consume energy to move, hold similar potential for man-made materials controlled by forces generated from within. Yet, their use as a powerhouse in materials science lacks. Here we show a massive acceleration of the annealing of a monolayer of passive beads by moderate addition of self-propelled microparticles. We rationalize our observations with a model of collisions that drive active fluctuations and activate the annealing. The experiment is quantitatively compared with Brownian dynamic simulations that further unveil a dynamical transition in the mechanism of annealing. Active dopants travel uniformly in the system or co-localize at the grain boundaries as a result of the persistence of their motion. Our findings uncover the potential of internal activity to control materials and lay the groundwork for the rise of materials science beyond equilibrium.}, author = {Ramananarivo, Sophie and Ducrot, Etienne and Palacci, Jérémie A}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Springer Nature}, title = {{Activity-controlled annealing of colloidal monolayers}}, doi = {10.1038/s41467-019-11362-y}, volume = {10}, year = {2019}, } @inproceedings{9261, abstract = {Bending-active structures are able to efficiently produce complex curved shapes starting from flat panels. The desired deformation of the panels derives from the proper selection of their elastic properties. Optimized panels, called FlexMaps, are designed such that, once they are bent and assembled, the resulting static equilibrium configuration matches a desired input 3D shape. The FlexMaps elastic properties are controlled by locally varying spiraling geometric mesostructures, which are optimized in size and shape to match the global curvature (i.e., bending requests) of the target shape. The design pipeline starts from a quad mesh representing the input 3D shape, which defines the edge size and the total amount of spirals: every quad will embed one spiral. Then, an optimization algorithm tunes the geometry of the spirals by using a simplified pre-computed rod model. This rod model is derived from a non-linear regression algorithm which approximates the non-linear behavior of solid FEM spiral models subject to hundreds of load combinations. This innovative pipeline has been applied to the project of a lightweight plywood pavilion named FlexMaps Pavilion, which is a single-layer piecewise twisted arc that fits a bounding box of 3.90x3.96x3.25 meters.}, author = {Laccone, Francesco and Malomo, Luigi and Perez Rodriguez, Jesus and Pietroni, Nico and Ponchio, Federico and Bickel, Bernd and Cignoni, Paolo}, booktitle = {IASS Symposium 2019 - 60th Anniversary Symposium of the International Association for Shell and Spatial Structures; Structural Membranes 2019 - 9th International Conference on Textile Composites and Inflatable Structures, FORM and FORCE}, isbn = {9788412110104}, issn = {2518-6582}, location = {Barcelona, Spain}, pages = {509--515}, publisher = {International Center for Numerical Methods in Engineering}, title = {{FlexMaps Pavilion: A twisted arc made of mesostructured flat flexible panels}}, year = {2019}, }