TY - JOUR AB - Quasiparticle excitations can compromise the performance of superconducting devices, causing high-frequency dissipation, decoherence in Josephson qubits, and braiding errors in proposed Majorana-based topological quantum computers. Quasiparticle dynamics have been studied in detail in metallic superconductors but remain relatively unexplored in semiconductor-superconductor structures, which are now being intensely pursued in the context of topological superconductivity. To this end, we use a system comprising a gate-confined semiconductor nanowire with an epitaxially grown superconductor layer, yielding an isolated, proximitized nanowire segment. We identify bound states in the semiconductor by means of bias spectroscopy, determine the characteristic temperatures and magnetic fields for quasiparticle excitations, and extract a parity lifetime (poisoning time) of the bound state in the semiconductor exceeding 10 ms. AU - Higginbotham, Andrew P AU - Albrecht, S M AU - Kiršanskas, Gediminas AU - Chang, W AU - Kuemmeth, Ferdinand AU - Krogstrup, Peter AU - Jespersen, Thomas AU - Nygård, Jesper AU - Flensberg, Karsten AU - Marcus, Charles ID - 99 IS - 12 JF - Nature Physics TI - Parity lifetime of bound states in a proximitized semiconductor nanowire VL - 11 ER - TY - JOUR AB - In this note, we consider the dynamics associated to a perturbation of an integrable Hamiltonian system in action-angle coordinates in any number of degrees of freedom and we prove the following result of ``micro-diffusion'': under generic assumptions on $ h$ and $ f$, there exists an orbit of the system for which the drift of its action variables is at least of order $ \sqrt {\varepsilon }$, after a time of order $ \sqrt {\varepsilon }^{-1}$. The assumptions, which are essentially minimal, are that there exists a resonant point for $ h$ and that the corresponding averaged perturbation is non-constant. The conclusions, although very weak when compared to usual instability phenomena, are also essentially optimal within this setting. AU - Bounemoura, Abed AU - Kaloshin, Vadim ID - 8495 IS - 4 JF - Proceedings of the American Mathematical Society SN - 0002-9939 TI - A note on micro-instability for Hamiltonian systems close to integrable VL - 144 ER - TY - JOUR AB - Proteases play important roles in many biologic processes and are key mediators of cancer, inflammation, and thrombosis. However, comprehensive and quantitative techniques to define the substrate specificity profile of proteases are lacking. The metalloprotease ADAMTS13 regulates blood coagulation by cleaving von Willebrand factor (VWF), reducing its procoagulant activity. A mutagenized substrate phage display library based on a 73-amino acid fragment of VWF was constructed, and the ADAMTS13-dependent change in library complexity was evaluated over reaction time points, using high-throughput sequencing. Reaction rate constants (kcat/KM) were calculated for nearly every possible single amino acid substitution within this fragment. This massively parallel enzyme kinetics analysis detailed the specificity of ADAMTS13 and demonstrated the critical importance of the P1-P1' substrate residues while defining exosite binding domains. These data provided empirical evidence for the propensity for epistasis within VWF and showed strong correlation to conservation across orthologs, highlighting evolutionary selective pressures for VWF. AU - Kretz, Colin A AU - Dai, Manhong AU - Soylemez, Onuralp AU - Yee, Andrew AU - Desch, Karl C AU - Siemieniak, David R AU - Tomberg, Kärt AU - Fyodor Kondrashov AU - Meng, Fan AU - Ginsburg, David B ID - 866 IS - 30 JF - PNAS TI - Massively parallel enzyme kinetics reveals the substrate recognition landscape of the metalloprotease ADAMTS13 VL - 112 ER - TY - JOUR AB - The factors that determine the tempo and mode of protein evolution continue to be a central question in molecular evolution. Traditionally, studies of protein evolution focused on the rates of amino acid substitutions. More recently, with the availability of sequence data and advanced experimental techniques, the focus of attention has shifted toward the study of evolutionary trajectories and the overall layout of protein fitness landscapes. In this review we describe the effect of epistasis on the topology of evolutionary pathways that are likely to be found in fitness landscapes and develop a simple theory to connect the number of maladapted genotypes to the topology of fitness landscapes with epistatic interactions. Finally, we review recent studies that have probed the extent of epistatic interactions and have begun to chart the fitness landscapes in protein sequence space. AU - Kondrashov, Dmitry A AU - Fyodor Kondrashov ID - 886 IS - 1 JF - Trends in Genetics TI - Topological features of rugged fitness landscapes in sequence space VL - 31 ER - TY - JOUR AB - MCM2 is a subunit of the replicative helicase machinery shown to interact with histones H3 and H4 during the replication process through its N-terminal domain. During replication, this interaction has been proposed to assist disassembly and assembly of nucleosomes on DNA. However, how this interaction participates in crosstalk with histone chaperones at the replication fork remains to be elucidated. Here, we solved the crystal structure of the ternary complex between the histone-binding domain of Mcm2 and the histones H3-H4 at 2.9 Å resolution. Histones H3 and H4 assemble as a tetramer in the crystal structure, but MCM2 interacts only with a single molecule of H3-H4. The latter interaction exploits binding surfaces that contact either DNA or H2B when H3-H4 dimers are incorporated in the nucleosome core particle. Upon binding of the ternary complex with the histone chaperone ASF1, the histone tetramer dissociates and both MCM2 and ASF1 interact simultaneously with the histones forming a 1:1:1:1 heteromeric complex. Thermodynamic analysis of the quaternary complex together with structural modeling support that ASF1 and MCM2 could form a chaperoning module for histones H3 and H4 protecting them from promiscuous interactions. This suggests an additional function for MCM2 outside its helicase function as a proper histone chaperone connected to the replication pathway. AU - Richet, Nicolas AU - Liu, Danni AU - Legrand, Pierre AU - Velours, Christophe AU - Corpet, Armelle AU - Gaubert, Albane AU - Bakail, May M AU - Moal-Raisin, Gwenaelle AU - Guerois, Raphael AU - Compper, Christel AU - Besle, Arthur AU - Guichard, Berengère AU - Almouzni, Genevieve AU - Ochsenbein, Françoise ID - 9017 IS - 3 JF - Nucleic Acids Research SN - 1362-4962 TI - Structural insight into how the human helicase subunit MCM2 may act as a histone chaperone together with ASF1 at the replication fork VL - 43 ER -