Nitrone Spin Traps for Biological Studies. (Volumes I and II).

A variety of aldonitrones for spin-trapping investigations have been synthesized, purified, and characterized. The alicyclic 5-member ring nitrones 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (TMPO) and its long-chain derivatives were prepared in 3 or 4 steps. The reaction steps involved a Michael addition to yield the $\gamma$-nitrocarbonyl compound, subsequent mild reduction with zinc and aqueous ammonium chloride to yield the cyclic intermediate nitrone, a Grignard addition reaction to give the hydroxylamine, and finally copper-catalyzed aerial oxidation of the hydroxylamine to provide the aldonitrone. Poor overall yields were obtained. In contrast, the acyclic aromatic nitrone $\alpha$-phenyl-N-tert-butyl nitrone (PBN) and its derivatives were prepared in good overall yields using two procedures that involved the condensation of the appropriate aromatic aldehyde with N-tert-butylhydroxylamine. The facile, one-step synthesis developed in this laboratory provided large quantities of PBN and some derivatives without contamination from starting aldehydes. This method generates the requisite hydroxylamine in situ (mild reduction of the nitro compound with zinc and acetic acid in aqueous ethanol) and thereby eliminates the need to prepare it separately before use. The investigations of the radical-scavenging abilities of these spin traps in homogeneous solution showed that a variety of oxygen- and carbon-centered radicals as well as hydrogen atoms could be trapped and characterized by electron paramagnetic resonance (EPR) spectroscopy as long-lived nitroxyl radicals. In heterogeneous micellar solution, DMPO and PBN were the best traps for surveying a number of radicals generated in different regions of the micelle. The long-chain, lipophilic derivatives of TMPO and PBN were ineffective in trapping radicals in micellar solution. The studies also revealed that the addition of bulky carbon-centered radicals to the nitrone function of TMPO derivatives is stereoselective and affords only one of the two possible geometric isomers of the resulting nitroxyl radical. The addition of oxygen-centered radicals, unhindered carbon-centered radicals, and hydrogen atoms is non-stereoselective and can afford both geometric isomers. Using the spin-trapping technique, we detected no free radicals during photobleaching of the visual pigment rhodopsin under various partial pressures of oxygen. This along with other data indicates that photo-excited rhodopsin does not initiate retinal damage

Multiplexed telecommunication-band quantum networking with atom arrays in optical cavities

The realization of a quantum network node of matter-based qubits compatible with telecommunication-band operation and large-scale quantum information processing is an outstanding challenge that has limited the potential of elementary quantum networks. We propose a platform for interfacing quantum processors comprising neutral atom arrays with telecommunication-band photons in a multiplexed network architecture. The use of a large atom array instead of a single atom mitigates the deleterious effects of two-way communication and improves the entanglement rate between two nodes by nearly two orders of magnitude. Furthermore, this system simultaneously provides the ability to perform high-fidelity deterministic gates and readout within each node, opening the door to quantum repeater and purification protocols to enhance the length and fidelity of the network, respectively. Using intermediate nodes as quantum repeaters, we demonstrate the feasibility of entanglement distribution over ${\approx}1500\phantom{\rule{0.28em}{0ex}}\text{km}$ based on realistic assumptions, providing a blueprint for a transcontinental network. Finally, we demonstrate that our platform can distribute ${\gtrsim}25$ Bell pairs over metropolitan distances, which could serve as the backbone of a distributed fault-tolerant quantum computer

Active cancellation of servo-induced noise on stabilized lasers via feedforward

Many precision laser applications require active frequency stabilization. However, such stabilization loops operate by pushing noise to frequencies outside their bandwidth, leading to large "servo bumps" that can have deleterious effects for certain applications. The prevailing approach to filtering this noise is to pass the laser through a high finesse optical cavity, which places constraints on the system design. Here, we propose and demonstrate a different approach where a frequency error signal is derived from a beat note between the laser and the light that passes through the reference cavity. The phase noise derived from this beat note is fed forward to an electro-optic modulator after the laser, carefully accounting for relative delay, for real-time frequency correction. With a Hz-linewidth laser, we show $\gtrsim20$ dB noise suppression at the peak of the servo bump ($\approx250$ kHz), and a noise suppression bandwidth of $\approx5$ MHz -- well beyond the servo bump. By simulating the Rabi dynamics of a two-level atom with our measured data, we demonstrate substantial improvements to the pulse fidelity over a wide range of Rabi frequencies. Our approach offers a simple and versatile method for obtaining a clean spectrum of a narrow linewidth laser, as required in many emerging applications of cold atoms, and is readily compatible with commercial systems that may even include wavelength conversion

Repetitive readout and real-time control of nuclear spin qubits in 171^{171}Yb atoms

We demonstrate high fidelity repetitive projective measurements of nuclear spin qubits in an array of neutral ytterbium-171 ($^{171}$Yb) atoms. We show that the qubit state can be measured with a fidelity of 0.995(4) under a condition that leaves it in the state corresponding to the measurement outcome with a probability of 0.993(6) for a single tweezer and 0.981(4) averaged over the array. This is accomplished by near-perfect cyclicity of one of the nuclear spin qubit states with an optically excited state under a magnetic field of $B=58$ G, resulting in a bright/dark contrast of $\approx10^5$ during fluorescence readout. The performance improves further as $\sim1/B^2$. The state-averaged readout survival of 0.98(1) is limited by off-resonant scattering to dark states and can be addressed via post-selection by measuring the atom number at the end of the circuit, or during the circuit by performing a measurement of both qubit states. We combine projective measurements with high-fidelity rotations of the nuclear spin qubit via an AC magnetic field to explore several paradigmatic scenarios, including the non-commutivity of measurements in orthogonal bases, and the quantum Zeno mechanism in which measurements "freeze" coherent evolution. Finally, we employ real-time feedforward to repetitively deterministically prepare the qubit in the $+z$ or $-z$ direction after initializing it in an orthogonal basis and performing a projective measurement in the $z$-basis. These capabilities constitute an important step towards adaptive quantum circuits with atom arrays, such as in measurement-based quantum computation, fast many-body state preparation, holographic dynamics simulations, and quantum error correction

Insurance Status and Tumor Necrosis Factor Inhibitor Initiation Among Children With Juvenile Idiopathic Arthritis in the CARRA Registry.

OBJECTIVE: Prompt escalation to tumor necrosis factor inhibitors (TNFis) is recommended for children with juvenile idiopathic arthritis (JIA) and ongoing disease activity despite treatment with conventional disease-modifying antirheumatic drugs (cDMARDs). It is unknown whether these recommendations are equitably followed for children with different insurance types. We assessed the association of insurance coverage on the odds and timing of TNFi use. METHODS: We conducted a retrospective study of children with newly diagnosed JIA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We compared the odds of starting a TNFi in the first year and time from cDMARD to TNFi initiation between those with public and private insurance. RESULTS: We identified 1086 children with new JIA diagnoses. Publicly insured children had significantly higher active joint counts and parent/patient global assessment scores at the enrollment visit. They were also more likely to have polyarticular arthritis compared to those with private insurance. Odds of any TNFi use in the first year did not differ between publicly and privately insured children. Publicly insured children were escalated from cDMARD to TNFi more quickly than privately insured children. CONCLUSION: Children who were publicly insured had more severe disease and polyarticular involvement at registry enrollment compared to those who were privately insured. Whereas overall TNFi use did not differ between children with different insurance types, publicly insured children were escalated more quickly, consistent with their increased disease severity. Further research is needed to determine why insurance coverage type is associated with disease severity, including how other socioeconomic factors affect presentation to care

An architecture for two-qubit encoding in neutral ytterbium-171 atoms

We present an architecture for encoding two qubits within the optical "clock" transition and nuclear spin-1/2 degree of freedom of neutral ytterbium-171 atoms. Inspired by recent high-fidelity control of all pairs of states within this four-dimensional ququart space, we present a toolbox for intra-ququart (single atom) one- and two-qubit gates, inter-ququart (two atom) Rydberg-based two- and four-qubit gates, and quantum nondemolition (QND) readout. We then use this toolbox to demonstrate the advantages of the ququart encoding for entanglement distillation and quantum error correction which exhibit superior hardware efficiency and better performance in some cases since fewer two-atom (Rydberg-based) operations are required. Finally, leveraging single-state QND readout in our ququart encoding, we present a unique approach to studying interactive circuits as well as to realizing a symmetry protected topological phase of a spin-1 chain with a shallow, constant-depth circuit. These applications are all within reach of recent experiments with neutral ytterbium-171 atom arrays or with several trapped ion species.Comment: 22 pages, 14 figure

Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum

BACKGROUND: Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5 0 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness

Immunomodulation with Recombinant Interferon-γ1b in Pulmonary Tuberculosis

BACKGROUND:Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-gamma1b (rIFN-gammab) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance. METHODOLOGY/PRINCIPAL FINDINGS:We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-gamma1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1beta, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-gamma1b group from baseline to week 16. Both rIFN-gamma1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-gamma1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-gamma1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-gamma1b versus DOTS alone. CONCLUSION:Recombinant interferon-gamma1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms. TRIAL REGISTRATION:ClinicalTrials.gov NCT00201123

An investigation of friction coefficients in the inlet length of smooth round tubes

M.S.Mario J. Gogli