Reactive oxygen species induce expression of vascular endothelial growth factor in chondrocytes and human articular cartilage explants

Vascular endothelial growth factor (VEGF) promotes cartilage-degrading pathways, and there is evidence for the involvement of reactive oxygen species (ROS) in cartilage degeneration. However, a relationship between ROS and VEGF has not been reported. Here, we investigate whether the expression of VEGF is modulated by ROS. Aspirates of synovial fluid from patients with osteoarthritis (OA) were examined for intra-articular VEGF using ELISA. Immortalized C28/I2 chondrocytes and human knee cartilage explants were exposed to phorbol myristate acetate (PMA; 0–20 μg/ml), which is a ROS inducer, or 3-morpholino-sydnonimine hydrochloride (SIN-1; 0–20 μM), which is a ROS donor. The levels of VEGF protein and nitric oxide (NO) production were determined in the medium supernatant, using ELISA and Griess reagent, respectively. Gene expression of VEGF-121 and VEGF-165 was determined by splice variant RT-PCR. Expression of VEGF and VEGF receptors (VEGFR-1 and VEGFR-2) was quantified by real-time RT-PCR. Synovial fluid from OA patients revealed markedly elevated levels of VEGF. Common RT-PCR revealed that the splice variants were present in both immortalized chondrocytes and cartilage discs. In immortalized chondrocytes, stimulation with PMA or SIN-1 caused increases in the levels of VEGF, VEGFR-1 and VEGFR-2 mRNA expression. Cartilage explants produced similar results, but VEGFR-1 was only detectable after stimulation with SIN-1. Stimulation with PMA or SIN-1 resulted in a dose-dependent upregulation of the VEGF protein (as determined using ELISA) and an increase in the level of NO in the medium. Our findings indicate ROS-mediated induction of VEGF and VEGF receptors in chondrocytes and cartilage explants. These results demonstrate a relationship between ROS and VEGF as multiplex mediators in articular cartilage degeneration

Improved placement precision of implanted donor spin qubits in silicon using molecule ions

Donor spins in silicon-28 ($^{28}$Si) are among the most performant qubits in the solid state, offering record coherence times and gate fidelities above 99%. Donor spin qubits can be fabricated using the semiconductor-industry compatible method of deterministic ion implantation. Here we show that the precision of this fabrication method can be boosted by implanting molecule ions instead of single atoms. The bystander ions, co-implanted with the dopant of interest, carry additional kinetic energy and thus increase the detection confidence of deterministic donor implantation employing single ion detectors to signal the induced electron-hole pairs. This allows the placement uncertainty of donor qubits to be minimised without compromising on detection confidence. We investigate the suitability of phosphorus difluoride (PF$_2^+$) molecule ions to produce high quality P donor qubits. Since $^{19}$F nuclei have a spin of $I = 1/2$, it is imperative to ensure that they do not hyperfine couple to P donor electrons as they would cause decoherence by adding magnetic noise. Using secondary ion mass spectrometry, we confirm that F diffuses away from the active region of qubit devices while the P donors remain close to their original location during a donor activation anneal. PF$_2$-implanted qubit devices were then fabricated and electron spin resonance (ESR) measurements were performed on the P donor electron. A pure dephasing time of $T_2^* = 20.5 \pm 0.5$ $\mu$s and a coherence time of $T_2^{Hahn} = 424 \pm 5$ $\mu$s were extracted for the P donor electron-values comparable to those found in previous P-implanted qubit devices. Closer investigation of the P donor ESR spectrum revealed that no $^{19}$F nuclear spins were found in the vicinity of the P donor. Molecule ions therefore show great promise for producing high-precision deterministically-implanted arrays of long-lived donor spin qubits.Comment: 8 pages, 5 figures, 1 tabl

Beating the thermal limit of qubit initialization with a Bayesian Maxwell's demon

Fault-tolerant quantum computing requires initializing the quantum register in a well-defined fiducial state. In solid-state systems, this is typically achieved through thermalization to a cold reservoir, such that the initialization fidelity is fundamentally limited by temperature. Here, we present a method of preparing a fiducial quantum state with a confidence beyond the thermal limit. It is based on real time monitoring of the qubit through a negative-result measurement -- the equivalent of a `Maxwell's demon' that triggers the experiment only upon the appearance of a qubit in the lowest-energy state. We experimentally apply it to initialize an electron spin qubit in silicon, achieving a ground-state initialization fidelity of 98.9(4)%, corresponding to a 20$\times$ reduction in initialization error compared to the unmonitored system. A fidelity approaching 99.9% could be achieved with realistic improvements in the bandwidth of the amplifier chain or by slowing down the rate of electron tunneling from the reservoir. We use a nuclear spin ancilla, measured in quantum nondemolition mode, to prove the value of the electron initialization fidelity far beyond the intrinsic fidelity of the electron readout. However, the method itself does not require an ancilla for its execution, saving the need for additional resources. The quantitative analysis of the initialization fidelity reveals that a simple picture of spin-dependent electron tunneling does not correctly describe the data. Our digital `Maxwell's demon' can be applied to a wide range of quantum systems, with minimal demands on control and detection hardware.Comment: 15 pages, 7 figure

Conditional quantum operation of two exchange-coupled single-donor spin qubits in a MOS-compatible silicon device

Silicon nanoelectronic devices can host single-qubit quantum logic operations with fidelity better than 99.9%. For the spins of an electron bound to a single donor atom, introduced in the silicon by ion implantation, the quantum information can be stored for nearly 1 second. However, manufacturing a scalable quantum processor with this method is considered challenging, because of the exponential sensitivity of the exchange interaction that mediates the coupling between the qubits. Here we demonstrate the conditional, coherent control of an electron spin qubit in an exchange-coupled pair of $^{31}$P donors implanted in silicon. The coupling strength, $J = 32.06 \pm 0.06$ MHz, is measured spectroscopically with unprecedented precision. Since the coupling is weaker than the electron-nuclear hyperfine coupling $A \approx 90$ MHz which detunes the two electrons, a native two-qubit Controlled-Rotation gate can be obtained via a simple electron spin resonance pulse. This scheme is insensitive to the precise value of $J$, which makes it suitable for the scale-up of donor-based quantum computers in silicon that exploit the Metal-Oxide-Semiconductor fabrication protocols commonly used in the classical electronics industry.Comment: 10 pages, 5 figures, plus Supplementary Information. v2 contains additional references, and a simpler explanation of two-qubit CROT gates for donors in silico

Navigating the 16-dimensional Hilbert space of a high-spin donor qudit with electric and magnetic fields

Efficient scaling and flexible control are key aspects of useful quantum computing hardware. Spins in semiconductors combine quantum information processing with electrons, holes or nuclei, control with electric or magnetic fields, and scalable coupling via exchange or dipole interaction. However, accessing large Hilbert space dimensions has remained challenging, due to the short-distance nature of the interactions. Here, we present an atom-based semiconductor platform where a 16-dimensional Hilbert space is built by the combined electron-nuclear states of a single antimony donor in silicon. We demonstrate the ability to navigate this large Hilbert space using both electric and magnetic fields, with gate fidelity exceeding 99.8% on the nuclear spin, and unveil fine details of the system Hamiltonian and its susceptibility to control and noise fields. These results establish high-spin donors as a rich platform for practical quantum information and to explore quantum foundations.Comment: 31 pages and 19 figures including Supplementary Material

Precision tomography of a three-qubit electron-nuclear quantum processor in silicon

Nuclear spins were among the first physical platforms to be considered for quantum information processing, because of their exceptional quantum coherence and atomic-scale footprint. However, their full potential for quantum computing has not yet been realized, due to the lack of methods to link nuclear qubits within a scalable device combined with multi-qubit operations with sufficient fidelity to sustain fault-tolerant quantum computation. Here we demonstrate universal quantum logic operations using a pair of ion-implanted $^{31}$P nuclei in a silicon nanoelectronic device. A nuclear two-qubit controlled-Z gate is obtained by imparting a geometric phase to a shared electron spin, and used to prepare entangled Bell states with fidelities up to 94.2(2.7)%. The quantum operations are precisely characterised using gate set tomography (GST), yielding one-qubit gate fidelities up to 99.93(3)%, two-qubit gate fidelity of 99.21(14)% and two-qubit preparation/measurement fidelities of 98.95(4)%. These three metrics indicate that nuclear spins in silicon are approaching the performance demanded in fault-tolerant quantum processors. We then demonstrate entanglement between the two nuclei and the shared electron by producing a Greenberger-Horne-Zeilinger three-qubit state with 92.5(1.0)% fidelity. Since electron spin qubits in semiconductors can be further coupled to other electrons or physically shuttled across different locations, these results establish a viable route for scalable quantum information processing using nuclear spins.Comment: 27 pages, 14 figures, plus 20 pages supplementary information. v2 includes new and updated references, and minor text change

Tomography of entangling two-qubit logic operations in exchange-coupled donor electron spin qubits

Scalable quantum processors require high-fidelity universal quantum logic operations in a manufacturable physical platform. Donors in silicon provide atomic size, excellent quantum coherence and compatibility with standard semiconductor processing, but no entanglement between donor-bound electron spins has been demonstrated to date. Here we present the experimental demonstration and tomography of universal 1- and 2-qubit gates in a system of two weakly exchange-coupled electrons, bound to single phosphorus donors introduced in silicon by ion implantation. We surprisingly observe that the exchange interaction has no effect on the qubit coherence. We quantify the fidelity of the quantum operations using gate set tomography (GST), and we use the universal gate set to create entangled Bell states of the electrons spins, with fidelity ~ 93%, and concurrence 0.91 +/- 0.08. These results form the necessary basis for scaling up donor-based quantum computers

Daytime variation of perioperative myocardial injury in non-cardiac surgery and effect on outcome

Recently, daytime variation in perioperative myocardial injury (PMI) has been observed in patients undergoing cardiac surgery. We aim at investigating whether daytime variation also occurs in patients undergoing non-cardiac surgery.; In a prospective diagnostic study, we evaluated the presence of daytime variation in PMI in patients at increased cardiovascular risk undergoing non-cardiac surgery, as well as its possible impact on the incidence of acute myocardial infarction (AMI), and death during 1-year follow-up in a propensity score-matched cohort. PMI was defined as an absolute increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration of ≥14 ng/L from preoperative to postoperative measurements.; Of 1641 patients, propensity score matching defined 630 with similar baseline characteristics, half undergoing non-cardiac surgery in the morning (starting from 8:00 to 11:00) and half in the afternoon (starting from 14:00 to 17:00). There was no difference in PMI incidence between both groups (morning: 50, 15.8% (95% CI 12.3 to 20.3); afternoon: 52, 16.4% (95% CI 12.7 to 20.9), p=0.94), nor if analysing hs-cTnT release as a quantitative variable (median morning group: 3 ng/L (95% CI 1 to 7 ng/L); median afternoon group: 2 ng/L (95% CI 0 to 7 ng/L; p=0.16). During 1-year follow-up, the incidence of AMI was 1.2% (95% CI 0.4% to 3.2%) among morning surgeries versus 4.1% (95% CI 2.3% to 6.9%) among the afternoon surgeries (corrected HR for afternoon surgery 3.44, bootstrapped 95% CI 1.33 to 10.49, p log-rank=0.03), whereas no difference in mortality emerged (p=0.70).; Although there is no daytime variation in PMI in patients undergoing non-cardiac surgery, the incidence of AMI during follow-up is increased in afternoon surgeries and requires further study.; NCT02573532;Results