Quantum supremacy using a programmable superconducting processor.

The promise of quantum computers is that certain computational tasks might be executed exponentially faster on a quantum processor than on a classical processor1. A fundamental challenge is to build a high-fidelity processor capable of running quantum algorithms in an exponentially large computational space. Here we report the use of a processor with programmable superconducting qubits2-7 to create quantum states on 53 qubits, corresponding to a computational state-space of dimension 253 (about 1016). Measurements from repeated experiments sample the resulting probability distribution, which we verify using classical simulations. Our Sycamore processor takes about 200 seconds to sample one instance of a quantum circuit a million times-our benchmarks currently indicate that the equivalent task for a state-of-the-art classical supercomputer would take approximately 10,000 years. This dramatic increase in speed compared to all known classical algorithms is an experimental realization of quantum supremacy8-14 for this specific computational task, heralding a much-anticipated computing paradigm.

Measurement of Small Photon Numbers in Circuit QED Resonators.

Off-resonant interaction of fluctuating photons in a resonator with a qubit increases the qubit dephasing rate. We use this effect to measure a small average number of intracavity photons that are coherently or thermally driven. For spectral resolution, we do this by subjecting the qubit to a Carr-Purcell-Meiboom-Gill sequence and record the qubit dephasing rate for various periods between qubit π pulses. The recorded data is then analyzed with formulas for the photon-induced dephasing rate derived for the non-Gaussian noise regime with an arbitrary ratio of the resonator dispersive shift to decay rate. We show that the presented Carr-Purcell-Meiboom-Gill dephasing rate formulas agree well with experimental results and demonstrate measurement of thermal and coherent photon populations at the level of a few 10^{-4}.

Model-Based Optimization of Superconducting Qubit Readout.

Measurement is an essential component of quantum algorithms, and for superconducting qubits it is often the most error prone. Here, we demonstrate model-based readout optimization achieving low measurement errors while avoiding detrimental side effects. For simultaneous and midcircuit measurements across 17 qubits, we observe 1.5% error per qubit with a 500 ns end-to-end duration and minimal excess reset error from residual resonator photons. We also suppress measurement-induced state transitions achieving a leakage rate limited by natural heating. This technique can scale to hundreds of qubits and be used to enhance the performance of error-correcting codes and near-term applications.

Correlators Exceeding One in Continuous Measurements of Superconducting Qubits.

We consider the effect of phase backaction on the correlator ⟨I(t)I(t+τ)⟩ for the output signal I(t) from continuous measurement of a qubit. We demonstrate that the interplay between informational and phase backactions in the presence of Rabi oscillations can lead to the correlator becoming larger than 1, even though |⟨I⟩|≤1. The correlators can be calculated using the generalized "collapse recipe," which we validate using the quantum Bayesian formalism. The recipe can be further generalized to the case of multitime correlators and arbitrary number of detectors, measuring non-commuting qubit observables. The theory agrees well with experimental results for continuous measurement of a transmon qubit. The experimental correlator exceeds the bound of 1 for a sufficiently large angle between the amplified and informational quadratures, causing the phase backaction. The demonstrated effect can be used to calibrate the quadrature misalignment.

Nuphar alkaloids induce very rapid apoptosis through a novel caspase-dependent but BAX/BAK-independent pathway.

Nuphar alkaloids, originally isolated from water lilies, induce apoptosis in mammalian cells in less than 1 h, making them possibly the fastest known inducers. However, the mechanism by which this rapid apoptosis occurs remains unknown. We have investigated canonical aspects of apoptosis to determine how the nuphar alkaloid, (+)-6-hydroxythiobinupharidine (6HTBN), induces apoptosis. 6HTBN induced rapid apoptosis in various leukemia, lymphoma, and carcinoma cell lines, suggesting that its mechanism is cell-type independent. It also circumvented resistance of patient-derived chronic lymphocytic leukemia cells generated by co-culture on survival-promoting stroma. Intriguingly, 6HTBN failed to induce apoptosis in platelets. The mechanism of apoptosis involves activation of caspase 9 and caspase 3, but not caspase 8 as previously reported. The release of cytochrome c from mitochondria occurred even in the absence of BAX/BAK and in cells that retained mitochondrial membrane potential. These results suggest a novel mechanism of apoptosis that has previously not been reported. The molecular target of the nuphar alkaloids remains to be determined.

Arrow of Time for Continuous Quantum Measurement.

We investigate the statistical arrow of time for a quantum system being monitored by a sequence of measurements. For a continuous qubit measurement example, we demonstrate that time-reversed evolution is always physically possible, provided that the measurement record is also negated. Despite this restoration of dynamical reversibility, a statistical arrow of time emerges, and may be quantified by the log-likelihood difference between forward and backward propagation hypotheses. We then show that such reversibility is a universal feature of nonprojective measurements, with forward or backward Janus measurement sequences that are time-reversed inverses of each other.

Stereoselective Synthesis and Biological Evaluation of C1-Epimeric and Desmethyl Monomeric Nuphar Analogues.

A class of monomeric nuphar analogues that are either epimeric at C1 and C1' or lack the naturally occurring methyl group at those positions were synthesized and evaluated for biological activity. The syntheses feature enantioselective vinylogous Mukaiyama-Mannich (vM-Mannich) reactions catalyzed by chiral phosphoric acids that proceed with excellent diastereoselectivity. Biological assays reveal that both the desmethyl and C1-epimeric monomeric nuphar analogous are able to induce rapid apoptosis.

Search of latent periodicity in amino acid sequences by means of genetic algorithm and dynamic programming.

The aim of this study was to show that amino acid sequences have a latent periodicity with insertions and deletions of amino acids in unknown positions of the analyzed sequence. Genetic algorithm, dynamic programming and random weight matrices were used to develop a new mathematical algorithm for latent periodicity search. A multiple alignment of periods was calculated with help of the direct optimization of the position-weight matrix without using pairwise alignments. The developed algorithm was applied to analyze amino acid sequences of a small number of proteins. This study showed the presence of latent periodicity with insertions and deletions in the amino acid sequences of such proteins, for which the presence of latent periodicity was not previously known. The origin of latent periodicity with insertions and deletions is discussed.

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

Many superconducting qubit systems use the dispersive interaction between the qubit and a coupled harmonic resonator to perform quantum state measurement. Previous works have found that such measurements can induce state transitions in the qubit if the number of photons in the resonator is too high. We investigate these transitions and find that they can push the qubit out of the two-level subspace, and that they show resonant behavior as a function of photon number. We develop a theory for these observations based on level crossings within the Jaynes-Cummings ladder, with transitions mediated by terms in the Hamiltonian that are typically ignored by the rotating wave approximation. We find that the most important of these terms comes from an unexpected broken symmetry in the qubit potential. We confirm the theory by measuring the photon occupation of the resonator when transitions occur while varying the detuning between the qubit and resonator.

Enantioselective Formal Syntheses of 11 Nuphar Alkaloids and Discovery of Potent Apoptotic Monomeric Analogues.

Concise, scalable, and enantioselective formal syntheses of eight dimeric and three monomeric nuphar alkaloids were achieved, along with the construction of a stereochemically diverse collection of the first known monomeric analogues having apoptotic activity. The syntheses involved the development of highly enantioselective Brønsted acid catalyzed vinylogous Mukaiyama-Mannich reactions, which feature the unprecedented use of a supersilyl group to control the regio-, enantio- and diastereoselectivity. Biological studies reveal that several of these novel nuphar analogues are even more potent than their dimeric natural product counterparts.

Total Syntheses and Biological Evaluation of Both Enantiomers of Several Hydroxylated Dimeric Nuphar Alkaloids.

Herein, we describe the first total syntheses of five members of the dimeric nuphar alkaloids: (+)-6,6'-dihydroxythiobinupharidine (+)-1 a, (+)-6-hydroxythiobinupharidine (+)-1 b, (-)-6,6'-dihydroxythionuphlutine (-)-2 a, (-)-6,6'-dihydroxyneothiobinupharidine (-)-3 a, and (+)-6,6'-dihydroxyneothionuphlutine (+)-4 a. The latter two have not been found in nature. We have also made each of their enantiomers (-)-1 a-b, (+)-2 a, (+)-3 a, and (-)-4 a. The key step in these syntheses was the dimerization of an α-aminonitrile (a hydrolytically stable surrogate for its corresponding hemiaminal) with chiral Lewis acid complexes. We have also reassigned the literature structures of (+)-1 a-1 b­for those instances in which the NMR spectra were obtained in CD3OD­to their corresponding CD3O-adducts. Our efforts provide for the first time apoptosis data for (-)-3 a, (+)-4 a, and all five non-natural enantiomers prepared. The data indicate high apoptotic activity regardless of the enantiomer or relative stereochemical configuration at C7 and C7'.

To lie or to tell the truth? The influence of processing the opponent's feedback on the forthcoming choice.

Introduction: The brain mechanisms of deceptive behavior are relatively well studied, and the key brain regions involved in its processing were established. At the same time, the brain mechanisms underlying the processes of preparation for deception are less known. Methods: We studied BOLD-signal changes during the presentation of the opponent's feedback to a previous deceptive or honest action during the computer game. The goal of the game was to mislead the opponent either by means of deception or by means of telling the truth. Results: As a result, it was shown that several brain regions that were previously demonstrated as involved in deception execution, such as the left anterior cingulate cortex and anterior insula, also underlie processes related to deception preparation. Discussion: The results obtained also allowed us to suggest that brain regions responsible for performance monitoring, intention assessment, suppression of non-selected solutions, and reward processing could be involved in shaping future action selection and preparation for deception. By shedding light on the brain mechanisms underlying deception, our study contributes to a deeper understanding of this complex cognitive process. Furthermore, it emphasizes the significance of exploring brain mechanisms governing the choice between deception and truth at various stages of decision-making.

Optimizing quantum gates towards the scale of logical qubits.

A foundational assumption of quantum error correction theory is that quantum gates can be scaled to large processors without exceeding the error-threshold for fault tolerance. Two major challenges that could become fundamental roadblocks are manufacturing high-performance quantum hardware and engineering a control system that can reach its performance limits. The control challenge of scaling quantum gates from small to large processors without degrading performance often maps to non-convex, high-constraint, and time-dynamic control optimization over an exponentially expanding configuration space. Here we report on a control optimization strategy that can scalably overcome the complexity of such problems. We demonstrate it by choreographing the frequency trajectories of 68 frequency-tunable superconducting qubits to execute single- and two-qubit gates while mitigating computational errors. When combined with a comprehensive model of physical errors across our processor, the strategy suppresses physical error rates by ~3.7× compared with the case of no optimization. Furthermore, it is projected to achieve a similar performance advantage on a distance-23 surface code logical qubit with 1057 physical qubits. Our control optimization strategy solves a generic scaling challenge in a way that can be adapted to a variety of quantum operations, algorithms, and computing architectures.

Catch-disperse-release readout for superconducting qubits.

We analyze a single-shot readout for superconducting qubits via the controlled catch, dispersion, and release of a microwave field. A tunable coupler is used to decouple the microwave resonator from the transmission line during the dispersive qubit-resonator interaction, thus circumventing damping from the Purcell effect. We show that, if the qubit frequency tuning is sufficiently adiabatic, a fast high-fidelity qubit readout is possible, even in the strongly nonlinear dispersive regime. Interestingly, the Jaynes-Cummings nonlinearity leads to the quadrature squeezing of the resonator field below the standard quantum limit, resulting in a significant decrease of the measurement error.

Catch and release of microwave photon states.

We demonstrate a superconducting resonator with variable coupling to a measurement transmission line. The resonator coupling can be adjusted through zero to a photon emission rate 1000 times the intrinsic resonator decay rate. We demonstrate the catch and release of photons in the resonator, as well as control of nonclassical Fock states. We also demonstrate the dynamical control of the release waveform of photons from the resonator, a key functionality that will enable high-fidelity quantum state transfer between distant resonators or qubits.

Impaired Non-Selective Response Inhibition in Obsessive-Compulsive Disorder.

Two prominent features of obsessive-compulsive disorder (OCD) are the inability to inhibit intrusive thoughts and behaviors and pathological doubt or intolerance of uncertainty. Previous study showed that uncertain context modeled by equiprobable presentation of excitatory (Go) and inhibitory (NoGo) stimuli requires non-selective response inhibition in healthy subjects. In other words, it requires transient global inhibition triggered not only by excitatory stimuli but also by inhibitory stimuli. Meanwhile, it is unknown whether OCD patients show abnormal brain activity of the non-selective response inhibition system. In order to test this assumption, we performed an fMRI study with an equiprobable Go/NoGo task involving fourteen patients with OCD and compared them with 34 healthy controls. Patients with OCD showed pathological slowness in the Go/NoGo task. The non-selective response inhibition system in OCD included all brain areas seen in healthy controls and, in addition, involved the right anterior cingulate cortex (ACC) and the anterior insula/frontal operculum (AIFO). Moreover, a between-group comparison revealed hypoactivation of brain regions within cingulo-opercular and cortico-striato-thalamo-cortical (CSTC) circuits in OCD. Among hypoactivated areas, the right ACC and the right dorsolateral prefrontal cortex (DLPFC) were associated with non-selective inhibition. Furthermore, regression analysis showed that OCD slowness was associated with decreased activation in cingulate regions and two brain areas related to non-selective inhibition: the right DLPFC and the right inferior parietal lobule (IPL). These results suggest that non-selective response inhibition is impaired in OCD, which could be a potential explanation for a relationship between inhibitory deficits and the other remarkable characteristic of OCD known as intolerance of uncertainty.

Finite Element Parametric Design of Hallux Valgus Orthosis Based on Orthogonal Analysis.

OBJECTIVE: To design appropriate orthosis for hallux valgus, a difficult foot condition that affects a quarter of the body's bones, we need to clarify the numerical biomechanical features, which have not been established in previous biomechanical studies. Therefore, we constructed a finite element model of the bunion foot to investigate the orthopaedic force compensation mechanism. METHODS: A patient with moderate hallux valgus was recruited. CT imaging data in DICOM format were extracted for three-dimensional foot model reconstruction. In conjunction with the need for rapid design of bunion orthosis, a metatarsal force application sizing method based on an orthogonal test design was investigated. The orthogonal test design was used to obtain the hallux valgus angle (HVA) and the inter metatarsal angle (IMA) data for different force combinations. Based on the extreme difference analysis and analysis of variance of the test results, the influence of different force combinations on the bunion angle was quickly determined. RESULTS: The results showed that the stress concentration occurred mainly in the first metatarsal bone. The distribution trend was in the medial and lateral middle of the bone and gradually decreased to the dorsal base of the bone body. The greatest stress occurs in the cartilage between the phalanges and metatarsals. In 25 groups of simulation experiments, HVA was reduced from 27.7° to 13°, and IMA was reduced from 12.5° to 7.3°. CONCLUSION: Applying detailed orthopaedic force collocation to the first metatarsal column can effectively restore the mechanics and kinematics of hallux valgus, and provide a reference for the treatment of bunion valgus and the design of orthopaedic devices.

Dark triad personality traits are associated with decreased grey matter volumes in 'social brain' structures.

Introduction: Personality traits and the degree of their prominence determine various aspects of social interactions. Some of the most socially relevant traits constitute the Dark Triad - narcissism, psychopathy, and Machiavellianism - associated with antisocial behaviour, disregard for moral norms, and a tendency to manipulation. Sufficient data point at the existence of Dark Triad 'profiles' distinguished by trait prominence. Currently, neuroimaging studies have mainly concentrated on the neuroanatomy of individual dark traits, while the Dark Triad profile structure has been mostly overlooked. Methods: We performed a clustering analysis of the Dirty Dozen Dark Triad questionnaire scores of 129 healthy subjects using the k-means method. The variance ratio criterion (VRC) was used to determine the optimal number of clusters for the current data. The two-sample t-test within the framework of voxel-based morphometry (VBM) was performed to test the hypothesised differences in grey matter volume (GMV) for the obtained groups. Results: Clustering analysis revealed 2 groups of subjects, both with low-to-mid and mid-to-high levels of Dark Triad traits prominence. A further VBM analysis of these groups showed that a higher level of Dark Triad traits may manifest itself in decreased grey matter volumes in the areas related to emotional regulation (the dorsolateral prefrontal cortex, the cingulate cortex), as well as those included in the reward system (the ventral striatum, the orbitofrontal cortex). Discussion: The obtained results shed light on the neurobiological basis underlying social interactions associated with the Dark Triad and its profiles.

Evidence for non-selective response inhibition in uncertain contexts revealed by combined meta-analysis and Bayesian analysis of fMRI data.

Response inhibition is typically considered a brain mechanism selectively triggered by particular "inhibitory" stimuli or events. Based on recent research, an alternative non-selective mechanism was proposed by several authors. Presumably, the inhibitory brain activity may be triggered not only by the presentation of "inhibitory" stimuli but also by any imperative stimuli, including Go stimuli, when the context is uncertain. Earlier support for this notion was mainly based on the absence of a significant difference between neural activity evoked by equiprobable Go and NoGo stimuli. Equiprobable Go/NoGo design with a simple response time task limits potential confounds between response inhibition and accompanying cognitive processes while not preventing prepotent automaticity. However, previous neuroimaging studies used classical null hypothesis significance testing, making it impossible to accept the null hypothesis. Therefore, the current research aimed to provide evidence for the practical equivalence of neuronal activity in the Go and NoGo trials using Bayesian analysis of functional magnetic resonance imaging (fMRI) data. Thirty-four healthy participants performed a cued Go/NoGo task with an equiprobable presentation of Go and NoGo stimuli. To independently localize brain areas associated with response inhibition in similar experimental conditions, we performed a meta-analysis of fMRI studies using equal-probability Go/NoGo tasks. As a result, we observed overlap between response inhibition areas and areas that demonstrate the practical equivalence of neuronal activity located in the right dorsolateral prefrontal cortex, parietal cortex, premotor cortex, and left inferior frontal gyrus. Thus, obtained results favour the existence of non-selective response inhibition, which can act in settings of contextual uncertainty induced by the equal probability of Go and NoGo stimuli.

Functional Interactions Between Neural Substrates of Socio-cognitive Mechanisms Involved in Simple Deception and Manipulative Truth.

Introduction: Deceptive intentions may be realized by imparting false (simple deception) or true (manipulative truth) information. Both forms of deception require inferring others' thoughts and are underpinned by the theory of mind (TOM) neural system. Manipulative truth is thought to more strongly recruit these processes. However, the organization of functional interactions underlying simple deception and manipulative truth remains unclear. Materials and Methods: We performed psychophysiological interaction analysis for a key node in the TOM system, the right temporoparietal junction (rTPJ), using functional MRI data obtained from 23 volunteers (14 men and 9 women, age range 18-45 years) during the sender-receiver game. During the game, participants sent true, simple deceptive, or manipulative truthful messages to another player according to their own choice. A Bayesian approach to statistics was employed to perform statistical inference and define voxels with significant changes in functional interactions. Results: We observed functional interactions between nodes of the TOM system (bilateral TPJ, left precuneus, left dorsomedial prefrontal cortex, and right superior temporal sulcus) characterizing both forms of deception. We identified an increment in functional interactions of the rTPJ with the left TPJ (lTPJ) and right precuneus associated with manipulative truth. Furthermore, we demonstrated that a higher rate of manipulative truthful actions was associated with weaker functional interactions between the rTPJ and lTPJ, left precuneus, and left dorsomedial prefrontal cortex. Discussion: Compared with simple deception, manipulative truth is associated with a higher demand for socio-cognitive processes that contributes to the cognitive load of this form of deception. Impact statement This study contributes significantly to our understanding of the fundamental characteristics of socio-cognitive brain mechanisms. Analysis of psychophysiological interactions is highly relevant to the neurophysiology field to promote a shift from studying local activity changes in brain structures to elucidating the activity-related characteristics of functionally connected regions. The presented research for the first time demonstrates functional interactions between nodes of the theory of mind system underpinning deception through communication of false information and telling the truth to deceive (manipulative truth). Understanding the neural substrates of deception may be applied in the forensic field to develop techniques for detecting deception.