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  1. Abstract Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates’ formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellarmore »resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dissagregation activity is catalysed by the stress-responsive ER molecular chaperone – BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.« less
    Free, publicly-accessible full text available December 1, 2023
  2. Abstract Unconventional superconductors have Cooper pairs with lower symmetries than in conventional superconductors. In most unconventional superconductors, the additional symmetry breaking occurs in relation to typical ingredients such as strongly correlated Fermi liquid phases, magnetic fluctuations, or strong spin-orbit coupling in noncentrosymmetric structures. In this article, we show that the time-reversal symmetry breaking in the superconductor LaNiGa 2 is enabled by its previously unknown topological electronic band structure, with Dirac lines and a Dirac loop at the Fermi level. Two symmetry related Dirac points even remain degenerate under spin-orbit coupling. These unique topological features enable an unconventional superconducting gap inmore »which time-reversal symmetry can be broken in the absence of other typical ingredients. Our findings provide a route to identify a new type of unconventional superconductors based on nonsymmorphic symmetries and will enable future discoveries of topological crystalline superconductors.« less
    Free, publicly-accessible full text available December 1, 2023
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  5. Álvaro, Javier (Ed.)
    Free, publicly-accessible full text available November 1, 2022
  6. Abstract We introduce maximum-likelihood fragment tomography (MLFT) as an improved circuit cutting technique for running clustered quantum circuits on quantum devices with a limited number of qubits. In addition to minimizing the classical computing overhead of circuit cutting methods, MLFT finds the most likely probability distribution for the output of a quantum circuit, given the measurement data obtained from the circuit’s fragments. We demonstrate the benefits of MLFT for accurately estimating the output of a fragmented quantum circuit with numerical experiments on random unitary circuits. Finally, we show that circuit cutting can estimate the output of a clustered circuit withmore »higher fidelity than full circuit execution, thereby motivating the use of circuit cutting as a standard tool for running clustered circuits on quantum hardware.« less
    Free, publicly-accessible full text available December 1, 2022
  7. Abstract Fish adaption behaviors in complex environments are of great importance in improving the performance of underwater vehicles. This work presents a numerical study of the adaption behaviors of self-propelled fish in complex environments by developing a numerical framework of deep learning and immersed boundary–lattice Boltzmann method (IB–LBM). In this framework, the fish swimming in a viscous incompressible flow is simulated with an IB–LBM which is validated by conducting two benchmark problems including a uniform flow over a stationary cylinder and a self-propelled anguilliform swimming in a quiescent flow. Furthermore, a deep recurrent Q-network (DRQN) is incorporated with the IB–LBMmore »to train the fish model to adapt its motion to optimally achieve a specific task, such as prey capture, rheotaxis and Kármán gaiting. Compared to existing learning models for fish, this work incorporates the fish position, velocity and acceleration into the state space in the DRQN; and it considers the amplitude and frequency action spaces as well as the historical effects. This framework makes use of the high computational efficiency of the IB–LBM which is of crucial importance for the effective coupling with learning algorithms. Applications of the proposed numerical framework in point-to-point swimming in quiescent flow and position holding both in a uniform stream and a Kármán vortex street demonstrate the strategies used to adapt to different situations.« less
    Free, publicly-accessible full text available December 1, 2022
  8. Abstract Despite earning half of all science and engineering undergraduate degrees between 2007 and 2016 in the USA, women were awarded only 39% of earth science degrees in the same time period. In order to better understand why women are both choosing and staying in geology programs, we conducted a multi-case study of nine current female undergraduate geology majors at a large public university in the USA within a department that is at gender parity among its undergraduate majors. The main data source was audio-recorded critical incident interviews of each participant. Data from the interviews were analyzed through an iterativemore »coding process using codes adapted from previous studies that focused on factors both internal and external to the department. The students said that personal interests, influence by others outside of the department, and introductory classes attracted them to the geology program, but once declared, departmental factors such as relationship with faculty caused them to stay. We also found an emphasis on female role models, especially those teaching introductory courses. We believe this study offers important insights into the ways in which factors leading to recruitment and retention play out in the lived experiences of female geology majors.« less
    Free, publicly-accessible full text available December 1, 2022
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