Scalable quantum computing can become a reality with error correction, provided that coherent qubits can be constructed in large arrays1,2. The key premise is that physical errors can remain both ...small and sufficiently uncorrelated as devices scale, so that logical error rates can be exponentially suppressed. However, impacts from cosmic rays and latent radioactivity violate these assumptions. An impinging particle can ionize the substrate and induce a burst of quasiparticles that destroys qubit coherence throughout the device. High-energy radiation has been identified as a source of error in pilot superconducting quantum devices3–5, but the effect on large-scale algorithms and error correction remains an open question. Elucidating the physics involved requires operating large numbers of qubits at the same rapid timescales necessary for error correction. Here, we use space- and time-resolved measurements of a large-scale quantum processor to identify bursts of quasiparticles produced by high-energy rays. We track the events from their initial localized impact as they spread, simultaneously and severely limiting the energy coherence of all qubits and causing chip-wide failure. Our results provide direct insights into the impact of these damaging error bursts and highlight the necessity of mitigation to enable quantum computing to scale.Cosmic rays flying through superconducting quantum devices create bursts of excitations that destroy qubit coherence. Rapid, spatially resolved measurements of qubit error rates make it possible to observe the evolution of the bursts across a chip.
Scalable quantum computing can become a reality with error correction, provided coherent qubits can be constructed in large arrays. The key premise is that physical errors can remain both small and ...sufficiently uncorrelated as devices scale, so that logical error rates can be exponentially suppressed. However, energetic impacts from cosmic rays and latent radioactivity violate both of these assumptions. An impinging particle ionizes the substrate, radiating high energy phonons that induce a burst of quasiparticles, destroying qubit coherence throughout the device. High-energy radiation has been identified as a source of error in pilot superconducting quantum devices, but lacking a measurement technique able to resolve a single event in detail, the effect on large scale algorithms and error correction in particular remains an open question. Elucidating the physics involved requires operating large numbers of qubits at the same rapid timescales as in error correction, exposing the event's evolution in time and spread in space. Here, we directly observe high-energy rays impacting a large-scale quantum processor. We introduce a rapid space and time-multiplexed measurement method and identify large bursts of quasiparticles that simultaneously and severely limit the energy coherence of all qubits, causing chip-wide failure. We track the events from their initial localised impact to high error rates across the chip. Our results provide direct insights into the scale and dynamics of these damaging error bursts in large-scale devices, and highlight the necessity of mitigation to enable quantum computing to scale.
Realizing the potential of quantum computing will require achieving sufficiently low logical error rates. Many applications call for error rates in the \(10^{-15}\) regime, but state-of-the-art ...quantum platforms typically have physical error rates near \(10^{-3}\). Quantum error correction (QEC) promises to bridge this divide by distributing quantum logical information across many physical qubits so that errors can be detected and corrected. Logical errors are then exponentially suppressed as the number of physical qubits grows, provided that the physical error rates are below a certain threshold. QEC also requires that the errors are local and that performance is maintained over many rounds of error correction, two major outstanding experimental challenges. Here, we implement 1D repetition codes embedded in a 2D grid of superconducting qubits which demonstrate exponential suppression of bit or phase-flip errors, reducing logical error per round by more than \(100\times\) when increasing the number of qubits from 5 to 21. Crucially, this error suppression is stable over 50 rounds of error correction. We also introduce a method for analyzing error correlations with high precision, and characterize the locality of errors in a device performing QEC for the first time. Finally, we perform error detection using a small 2D surface code logical qubit on the same device, and show that the results from both 1D and 2D codes agree with numerical simulations using a simple depolarizing error model. These findings demonstrate that superconducting qubits are on a viable path towards fault tolerant quantum computing.
Interaction in quantum systems can spread initially localized quantum information into the many degrees of freedom of the entire system. Understanding this process, known as quantum scrambling, is ...the key to resolving various conundrums in physics. Here, by measuring the time-dependent evolution and fluctuation of out-of-time-order correlators, we experimentally investigate the dynamics of quantum scrambling on a 53-qubit quantum processor. We engineer quantum circuits that distinguish the two mechanisms associated with quantum scrambling, operator spreading and operator entanglement, and experimentally observe their respective signatures. We show that while operator spreading is captured by an efficient classical model, operator entanglement requires exponentially scaled computational resources to simulate. These results open the path to studying complex and practically relevant physical observables with near-term quantum processors.
Resistance training may differentially affect morphological adaptations along the length of uni-articular and bi-articular muscles. The purpose of this study was to compare changes in muscle ...morphology along the length of the rectus femoris (RF) and vastus lateralis (VL) in response to resistance training. Following a 2-wk preparatory phase, 15 resistance-trained men (24.0 ± 3.0 y, 90.0 ± 13.8 kg, 174.9 ± 20.7 cm) completed pre-training (PRE) assessments of muscle thickness (MT), pennation angle (PA), cross-sectional area (CSA), and echo-intensity in the RF and VL at 30, 50, and 70% of each muscle's length; fascicle length (FL) was estimated from respective measurements of MT and PA within each muscle and region. Participants then began a high intensity, low volume (4 x 3-5 repetitions, 3min rest) lower-body resistance training program, and repeated all PRE-assessments after 8 weeks (2 d ∙ wk-1) of training (POST). Although three-way (muscle RF, VL x region 30, 50, 70% x time PRE, POST) repeated measures analysis of variance did not reveal significant interactions for any assessment of morphology, significant simple (muscle x time) effects were observed for CSA (p = 0.002) and FL (p = 0.016). Specifically, average CSA changes favored the VL (2.96 ± 0.69 cm2, p < 0.001) over the RF (0.59 ± 0.20 cm2, p = 0.011), while significant decreases in average FL were noted for the RF (-1.03 ± 0.30 cm, p = 0.004) but not the VL (-0.05 ± 0.36 cm, p = 0.901). No other significant differences were observed. The findings of this study demonstrate the occurrence of non-homogenous adaptations in RF and VL muscle size and architecture following 8 weeks of high-intensity resistance training in resistance-trained men. However, training does not appear to influence region-specific adaptations in either muscle.
Fas ligand (FasL), expressed on the surface of activated cytotoxic T lymphocytes (CTLs), is the physiological ligand for the cell surface death receptor, Fas. The Fas-FasL engagement initiates ...diverse signaling pathways, including the extrinsic cell death signaling pathway, which is one of the effector mechanisms that CTLs use to kill tumor cells. Emerging clinical and experimental data indicate that Fas is essential for the efficacy of CAR-T cell immunotherapy. Furthermore, loss of Fas expression is a hallmark of human melanoma. We hypothesize that restoring Fas expression in tumor cells reverses human melanoma resistance to T cell cytotoxicity. DNA hypermethylation, at the FAS promoter, down-regulates FAS expression and confers melanoma cell resistance to FasL-induced cell death. Forced expression of Fas in tumor cells overcomes melanoma resistance to FasL-induced cell death in vitro. Lipid nanoparticle-encapsulated mouse Fas-encoding plasmid therapy eliminates Fas+ tumor cells and suppresses established melanoma growth in immune-competent syngeneic mice. Similarly, lipid nanoparticle-encapsulated human FAS-encoding plasmid (hCOFAS01) therapy significantly increases Fas protein levels on tumor cells of human melanoma patient-derived xenograft (PDX) and suppresses the established human melanoma PDX growth in humanized NSG mice. In human melanoma patients, FasL is expressed in activated and exhausted T cells, Fas mRNA level positively correlates with melanoma patient survival, and nivolumab immunotherapy increases FAS expression in tumor cells. Our data demonstrate that hCOFAS01 is an effective immunotherapeutic agent for human melanoma therapy with dual efficacy in increasing tumor cell FAS expression and in enhancing CTL tumor infiltration.
Patients with smoldering multiple myeloma (SMM) are observed until progression, but early treatment may improve outcomes. We conducted a phase II trial of elotuzumab, lenalidomide, and dexamethasone ...(EloLenDex) in patients with high-risk SMM and performed single-cell RNA and T cell receptor (TCR) sequencing on 149 bone marrow (BM) and peripheral blood (PB) samples from patients and healthy donors (HDs). We find that early treatment with EloLenDex is safe and effective and provide a comprehensive characterization of alterations in immune cell composition and TCR repertoire diversity in patients. We show that the similarity of a patient’s immune cell composition to that of HDs may have prognostic relevance at diagnosis and after treatment and that the abundance of granzyme K (GZMK)+ CD8+ effector memory T (TEM) cells may be associated with treatment response. Last, we uncover similarities between immune alterations observed in the BM and PB, suggesting that PB-based immune profiling may have diagnostic and prognostic utility.
Display omitted
•EloLenDex is associated with 4-year PFS of 89% in patients with high-risk SMM•Immune reactivity, post-therapy immune normalization are associated with longer PFS•Higher abundance of GZMK+ cytotoxic T cells is associated with longer PFS•Blood-based immune profiling detects immune dysregulation associated with disease
Sklavenitis-Pistofidis et al. report results of a phase II trial of EloLenDex in patients with high-risk smoldering multiple myeloma and use single-cell RNA sequencing to identify biomarkers of outcomes. They show that immune cell composition affects progression-free survival and that blood-based immune profiling can detect immune alterations observed in the bone marrow.
Phenotypes have been proposed as a method of characterizing subgroups based on biopsychosocial factors to identify responders to analgesic treatments. This study aimed to, first, confirm phenotypes ...in patients with low back pain receiving physical therapy based on an a priori set of factors used to derive subgroups in other pain populations. Second, an exploratory analysis examined if phenotypes differentiated pain and disability outcomes at four weeks of physical therapy. Fifty-five participants completed psychological questionnaires and pressure pain threshold (PPT). Somatization, anxiety, and depression domains of the Symptom-Checklist-90-Revised, and PPT, were entered into a hierarchical agglomerative cluster analysis with Ward's method to identify phenotypes. Repeated measures ANOVAs assessed pain ratings and disability by phenotype at four weeks. Three clusters emerged: 1) high emotional distress and pain sensitivity (n = 10), 2) low emotional distress (n = 34), 3) low pain sensitivity (n = 11). As an exploratory study, clusters did not differentiate pain ratings or disability after four weeks of physical therapy (p's>0.05). However, trends were observed as magnitude of change for pain varied by phenotype. This supports the characterization of homogenous subgroups based on a protocol conducted in the clinical setting with varying effect sizes noted by phenotype for short-term changes in pain. As an exploratory study, future studies should aim to repeat this trial in a larger sample of patients.
Although measles was eliminated in the United States in 2000, importations of the virus continue to cause outbreaks. We describe the epidemiologic features of an outbreak of measles that originated ...from two unvaccinated Amish men in whom measles was incubating at the time of their return to the United States from the Philippines and explore the effect of public health responses on limiting the spread of measles.
We performed descriptive analyses of data on demographic characteristics, clinical and laboratory evaluations, and vaccination coverage.
From March 24, 2014, through July 23, 2014, a total of 383 outbreak-related cases of measles were reported in nine counties in Ohio. The median age of case patients was 15 years (range, <1 to 53); a total of 178 of the case patients (46%) were female, and 340 (89%) were unvaccinated. Transmission took place primarily within households (68% of cases). The virus strain was genotype D9, which was circulating in the Philippines at the time of the reporting period. Measles-mumps-rubella (MMR) vaccination coverage with at least a single dose was estimated to be 14% in affected Amish households and more than 88% in the general (non-Amish) Ohio community. Containment efforts included isolation of case patients, quarantine of susceptible persons, and administration of the MMR vaccine to more than 10,000 persons. The spread of measles was limited almost exclusively to the Amish community (accounting for 99% of case patients) and affected only approximately 1% of the estimated 32,630 Amish persons in the settlement.
The key epidemiologic features of a measles outbreak in the Amish community in Ohio were transmission primarily within households, the small proportion of Amish people affected, and the large number of people in the Amish community who sought vaccination. As a result of targeted containment efforts, and high baseline coverage in the general community, there was limited spread beyond the Amish community. (Funded by the Ohio Department of Health and the Centers for Disease Control and Prevention.).