NADPH oxidase 2 inhibitors CPP11G and CPP11H attenuate endothelial cell inflammation & vessel dysfunction and restore mouse hind-limb flow.

First described as essential to the phagocytic activity of leukocytes, Nox2-derived ROS have emerged as mediators of a range of cellular and tissue responses across species from salubrious to deleterious consequences. Knowledge of their role in inflammation is limited, however. We postulated that TNFα-induced endothelial reactive oxygen species (ROS) generation and pro-inflammatory signaling would be ameliorated by targeting Nox2. Herein, we in silico-modelled two first-in-class Nox2 inhibitors developed in our laboratory, explored their cellular mechanism of action and tested their efficacy in in vitro and mouse in vivo models of inflammation. Our data show that these inhibitors (CPP11G and CPP11H) disrupted canonical Nox2 organizing factor, p47phox, translocation to Nox2 in the plasma membrane; and abolished ROS production, markedly attenuated stress-responsive MAPK signaling and downstream AP-1 and NFκB nuclear translocation in human cells. Consequently, cell adhesion molecule expression and monocyte adherence were significantly inhibited by both inhibitors. In vivo, TNFα-induced ROS and inflammation were ameliorated by targeted Nox2 inhibition, which, in turn, improved hind-limb blood flow. These studies identify a proximal role for Nox2 in propagated inflammatory signaling and support therapeutic value of Nox2 inhibitors in inflammatory disease

Impact of electrostatic crosstalk on spin qubits in dense CMOS quantum dot arrays

Quantum processors based on integrated nanoscale silicon spin qubits are a promising platform for highly scalable quantum computation. Current CMOS spin qubit processors consist of dense gate arrays to define the quantum dots, making them susceptible to crosstalk from capacitive coupling between a dot and its neighbouring gates. Small but sizeable spin-orbit interactions can transfer this electrostatic crosstalk to the spin g-factors, creating a dependence of the Larmor frequency on the electric field created by gate electrodes positioned even tens of nanometers apart. By studying the Stark shift from tens of spin qubits measured in nine different CMOS devices, we developed a theoretical frawework that explains how electric fields couple to the spin of the electrons in increasingly complex arrays, including those electric fluctuations that limit qubit dephasing times $T_2^*$. The results will aid in the design of robust strategies to scale CMOS quantum technology.Comment: 9 pages, 4 figure

High-fidelity operation and algorithmic initialisation of spin qubits above one kelvin

The encoding of qubits in semiconductor spin carriers has been recognised as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale. However, the operation of the large number of qubits required for advantageous quantum applications will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 kelvin, where the cooling power is orders of magnitude higher. Here, we tune up and operate spin qubits in silicon above 1 kelvin, with fidelities in the range required for fault-tolerant operation at such temperatures. We design an algorithmic initialisation protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies, and incorporate high-fidelity radio-frequency readout to achieve an initialisation fidelity of 99.34 per cent. Importantly, we demonstrate a single-qubit Clifford gate fidelity of 99.85 per cent, and a two-qubit gate fidelity of 98.92 per cent. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for high-fidelity operation to be possible, surmounting a major obstacle in the pathway to scalable and fault-tolerant quantum computation

High-fidelity spin qubit operation and algorithmic initialization above 1 K

The encoding of qubits in semiconductor spin carriers has been recognized as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale. However, the operation of the large number of qubits required for advantageous quantum applications will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 K, at which the cooling power is orders of magnitude higher. Here we tune up and operate spin qubits in silicon above 1 K, with fidelities in the range required for fault-tolerant operations at these temperatures. We design an algorithmic initialization protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies and incorporate radiofrequency readout to achieve fidelities up to 99.34% for both readout and initialization. We also demonstrate single-qubit Clifford gate fidelities up to 99.85% and a two-qubit gate fidelity of 98.92%. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for the high-fidelity operation to be possible, surmounting a main obstacle in the pathway to scalable and fault-tolerant quantum computation

Consistency of high-fidelity two-qubit operations in silicon

The consistency of entangling operations between qubits is essential for the performance of multi-qubit systems, and is a crucial factor in achieving fault-tolerant quantum processors. Solid-state platforms are particularly exposed to inconsistency due to the materials-induced variability of performance between qubits and the instability of gate fidelities over time. Here we quantify this consistency for spin qubits, tying it to its physical origins, while demonstrating sustained and repeatable operation of two-qubit gates with fidelities above 99% in the technologically important silicon metal-oxide-semiconductor (SiMOS) quantum dot platform. We undertake a detailed study of the stability of these operations by analysing errors and fidelities in multiple devices through numerous trials and extended periods of operation. Adopting three different characterisation methods, we measure entangling gate fidelities ranging from 96.8% to 99.8%. Our analysis tools also identify physical causes of qubit degradation and offer ways to maintain performance within tolerance. Furthermore, we investigate the impact of qubit design, feedback systems, and robust gates on implementing scalable, high-fidelity control strategies. These results highlight both the capabilities and challenges for the scaling up of spin-based qubits into full-scale quantum processors

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE