The characterization of γH2AX as a biomarker of genotoxicity in Oncorhynchus mykiss

Environmental contamination due to by-products and waste from industrial activities is a growing universal concern, especially regarding the impact on water and the aquaculture industry. Conventional tests to diagnose genotoxicity in fish include the comet assay and the quantification of micronuclei; however, these techniques are uninformative as to the nature of DNA damage occurring and the resulting gene response of the organism. This study involves characterizing the sensitivity of H2AX phosphorylation (γH2AX), a marker of double-stranded breaks, in rainbow trout using western blotting. I present RTbrain-W1 as an excellent fish cell line for characterizing γH2AX in response to the model DNA damaging agents, bleomycin, MMS, and 4-NQO. Bleomycin, which was not cytotoxic to RTbrain-W1, induced robust H2AX phosphorylation at 12.5 μg/mL that decreased with increasing concentrations up to 100 μg/mL after a 24h exposure. At 100 μg/mL, γH2AX levels were rapidly and strongly increased by 4h. Cells exposed to MMS and 4-NQO exhibited a contrasting dose response to bleomycin; increasing MMS and 4-NQO doses were cytotoxic and increased H2AX phosphorylation dose-dependently. In MMS-treated cells, γH2AX was first detectable at 0.01%, and an increase was observed in 0.015%-treated cells that remained stable through to a 0.025% treatment. Detectable induction with MMS at a concentration of 0.015% was much slower and weaker than bleomycin, and was first observed at 12h, increasing through 24h. Confocal microscopy was used to examine γH2AX localization throughout these concentrations of bleomycin and MMS, and dose responses following treatment after 24h. MMS-treated cells showed a dose dependent increase in γH2AX that was observed in the cytosol, likely due to cell death. Bleomycin-treated cells showed a strong dose-dependent increase of nuclear γH2AX localization that stabilized, and slightly decreased from 50 μg/mL to 400 μg/mL. Cells treated with 4-NQO showed a very subtle dose-dependent increase in γH2AX levels at 1000 nM, which was confirmed by densitometry to be a 2x increase. These results show the sensitivity of H2AX phosphorylation in response to different genotoxicants, and suggest that γH2AX may be a valuable biomarker for genotoxicity assays using rainbow trout cell lines.

VER-155008 induced Hsp70 proteins expression in fish cell cultures while impeding replication of two RNA viruses

The final publication is available at Elsevier via https://doi.org/10.1016/j.antiviral.2019.01.001 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The heat-shock protein 70 (Hsp70) inhibitor, VER-155008 (VER), was explored as a potential antiviral agent for two RNA viruses important to fish aquaculture, viral hemorrhagic septicemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Studies were done at a temperature of 14 °C, and with cell lines commonly used to propagate these viruses. These were respectively EPC from fathead minnow for VHSV and CHSE-214 from Chinook salmon embryo for IPNV. Additionally, both viruses were studied with the Atlantic salmon heart endothelial cell line ASHe. For both VHSV and IPNV, 25 μM VER impeded replication. This was evidenced by delays in the development of cytopathic effect (CPE) and the expression of viral proteins, N for VHSV and VP2 for IPNV, and by less production of viral RNA and of viral titre. As VER inhibits the activity of Hsp70 family members, these results suggest that VHSV and IPNV utilize one or more Hsp70s in their life cycles. Yet neither virus induced Hsp70. Surprisingly VER alone induced Hsp70, but whether this induction modulated VER's antiviral effects is unknown. Exploring this apparent paradox in the future should improve the usefulness of VER as an antiviral agent.Natural Science and Engineering Research Council, Grant 468298 - 14Elanco Canada Limite

Power spectrum for the small-scale Universe

The first objects to arise in a cold dark matter universe present a daunting challenge for models of structure formation. In the ultra small-scale limit, CDM structures form nearly simultaneously across a wide range of scales. Hierarchical clustering no longer provides a guiding principle for theoretical analyses and the computation time required to carry out credible simulations becomes prohibitively high. To gain insight into this problem, we perform high-resolution (N=720^3 - 1584^3) simulations of an Einstein-de Sitter cosmology where the initial power spectrum is P(k) propto k^n, with -2.5 < n < -1. Self-similar scaling is established for n=-1 and n=-2 more convincingly than in previous, lower-resolution simulations and for the first time, self-similar scaling is established for an n=-2.25 simulation. However, finite box-size effects induce departures from self-similar scaling in our n=-2.5 simulation. We compare our results with the predictions for the power spectrum from (one-loop) perturbation theory and demonstrate that the renormalization group approach suggested by McDonald improves perturbation theory's ability to predict the power spectrum in the quasilinear regime. In the nonlinear regime, our power spectra differ significantly from the widely used fitting formulae of Peacock & Dodds and Smith et al. and a new fitting formula is presented. Implications of our results for the stable clustering hypothesis vs. halo model debate are discussed. Our power spectra are inconsistent with predictions of the stable clustering hypothesis in the high-k limit and lend credence to the halo model. Nevertheless, the fitting formula advocated in this paper is purely empirical and not derived from a specific formulation of the halo model.Comment: 30 pages including 10 figures; accepted for publication in MNRA

Readout of a quantum processor with high dynamic range Josephson parametric amplifiers

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure

Measurement-Induced State Transitions in a Superconducting Qubit: Within the Rotating Wave Approximation

Superconducting qubits typically use a dispersive readout scheme, where a resonator is coupled to a qubit such that its frequency is qubit-state dependent. Measurement is performed by driving the resonator, where the transmitted resonator field yields information about the resonator frequency and thus the qubit state. Ideally, we could use arbitrarily strong resonator drives to achieve a target signal-to-noise ratio in the shortest possible time. However, experiments have shown that when the average resonator photon number exceeds a certain threshold, the qubit is excited out of its computational subspace, which we refer to as a measurement-induced state transition. These transitions degrade readout fidelity, and constitute leakage which precludes further operation of the qubit in, for example, error correction. Here we study these transitions using a transmon qubit by experimentally measuring their dependence on qubit frequency, average photon number, and qubit state, in the regime where the resonator frequency is lower than the qubit frequency. We observe signatures of resonant transitions between levels in the coupled qubit-resonator system that exhibit noisy behavior when measured repeatedly in time. We provide a semi-classical model of these transitions based on the rotating wave approximation and use it to predict the onset of state transitions in our experiments. Our results suggest the transmon is excited to levels near the top of its cosine potential following a state transition, where the charge dispersion of higher transmon levels explains the observed noisy behavior of state transitions. Moreover, occupation in these higher energy levels poses a major challenge for fast qubit reset

Overcoming leakage in scalable quantum error correction

Leakage of quantum information out of computational states into higher energy states represents a major challenge in the pursuit of quantum error correction (QEC). In a QEC circuit, leakage builds over time and spreads through multi-qubit interactions. This leads to correlated errors that degrade the exponential suppression of logical error with scale, challenging the feasibility of QEC as a path towards fault-tolerant quantum computation. Here, we demonstrate the execution of a distance-3 surface code and distance-21 bit-flip code on a Sycamore quantum processor where leakage is removed from all qubits in each cycle. This shortens the lifetime of leakage and curtails its ability to spread and induce correlated errors. We report a ten-fold reduction in steady-state leakage population on the data qubits encoding the logical state and an average leakage population of less than $1 \times 10^{-3}$ throughout the entire device. The leakage removal process itself efficiently returns leakage population back to the computational basis, and adding it to a code circuit prevents leakage from inducing correlated error across cycles, restoring a fundamental assumption of QEC. With this demonstration that leakage can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure

Suppressing quantum errors by scaling a surface code logical qubit

Practical quantum computing will require error rates that are well below what is achievable with physical qubits. Quantum error correction offers a path to algorithmically-relevant error rates by encoding logical qubits within many physical qubits, where increasing the number of physical qubits enhances protection against physical errors. However, introducing more qubits also increases the number of error sources, so the density of errors must be sufficiently low in order for logical performance to improve with increasing code size. Here, we report the measurement of logical qubit performance scaling across multiple code sizes, and demonstrate that our system of superconducting qubits has sufficient performance to overcome the additional errors from increasing qubit number. We find our distance-5 surface code logical qubit modestly outperforms an ensemble of distance-3 logical qubits on average, both in terms of logical error probability over 25 cycles and logical error per cycle ($2.914\%\pm 0.016\%$ compared to $3.028\%\pm 0.023\%$). To investigate damaging, low-probability error sources, we run a distance-25 repetition code and observe a $1.7\times10^{-6}$ logical error per round floor set by a single high-energy event ($1.6\times10^{-7}$ when excluding this event). We are able to accurately model our experiment, and from this model we can extract error budgets that highlight the biggest challenges for future systems. These results mark the first experimental demonstration where quantum error correction begins to improve performance with increasing qubit number, illuminating the path to reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references, Fig. S12, Table I

Measurement-induced entanglement and teleportation on a noisy quantum processor

Measurement has a special role in quantum theory: by collapsing the wavefunction it can enable phenomena such as teleportation and thereby alter the "arrow of time" that constrains unitary evolution. When integrated in many-body dynamics, measurements can lead to emergent patterns of quantum information in space-time that go beyond established paradigms for characterizing phases, either in or out of equilibrium. On present-day NISQ processors, the experimental realization of this physics is challenging due to noise, hardware limitations, and the stochastic nature of quantum measurement. Here we address each of these experimental challenges and investigate measurement-induced quantum information phases on up to 70 superconducting qubits. By leveraging the interchangeability of space and time, we use a duality mapping, to avoid mid-circuit measurement and access different manifestations of the underlying phases -- from entanglement scaling to measurement-induced teleportation -- in a unified way. We obtain finite-size signatures of a phase transition with a decoding protocol that correlates the experimental measurement record with classical simulation data. The phases display sharply different sensitivity to noise, which we exploit to turn an inherent hardware limitation into a useful diagnostic. Our work demonstrates an approach to realize measurement-induced physics at scales that are at the limits of current NISQ processors

Non-Abelian braiding of graph vertices in a superconducting processor

Indistinguishability of particles is a fundamental principle of quantum mechanics. For all elementary and quasiparticles observed to date - including fermions, bosons, and Abelian anyons - this principle guarantees that the braiding of identical particles leaves the system unchanged. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well developed mathematical description of non-Abelian anyons and numerous theoretical proposals, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. While efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasi-particles, superconducting quantum processors allow for directly manipulating the many-body wavefunction via unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons, we implement a generalized stabilizer code and unitary protocol to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of employing the anyons for quantum computation and utilize braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and - through the future inclusion of error correction to achieve topological protection - could open a path toward fault-tolerant quantum computing