Heterogeneous Vesicles with Phases having Different Preferred Curvatures: Shape Fluctuations and Mechanics of Active Deformations

We investigate the mechanics of heterogeneous vesicles having a collection of phase-separated domains with different preferred curvatures. We develop approaches to study at the coarse-grained level and continuum level the role of phase separation, elastic mechanics, and vesicle geometry. We investigate the elastic responses of vesicles both from passive shape fluctuations and from active deformations. We develop spectral analysis methods for analyzing passive shape fluctuations and further probe the mechanics through active deformations compressing heterogeneous vesicles between two flat plates or subjecting vesicles to insertion into slit-like channels. We find significant domain rearrangements can arise in heterogeneous vesicles in response to deformations. Relative to homogeneous vesicles, we find that heterogeneous vesicles can exhibit smaller resisting forces to compression and larger insertion times into channels. We introduce quantitative approaches for characterizing heterogeneous vesicles and how their mechanics can differ from homogeneous vesicles

Evolution of 1/f1/f Flux Noise in Superconducting Qubits with Weak Magnetic Fields

The microscopic origin of $1/f$ magnetic flux noise in superconducting circuits has remained an open question for several decades despite extensive experimental and theoretical investigation. Recent progress in superconducting devices for quantum information has highlighted the need to mitigate sources of qubit decoherence, driving a renewed interest in understanding the underlying noise mechanism(s). Though a consensus has emerged attributing flux noise to surface spins, their identity and interaction mechanisms remain unclear, prompting further study. Here we apply weak in-plane magnetic fields to a capacitively-shunted flux qubit (where the Zeeman splitting of surface spins lies below the device temperature) and study the flux-noise-limited qubit dephasing, revealing previously unexplored trends that may shed light on the dynamics behind the emergent $1/f$ noise. Notably, we observe an enhancement (suppression) of the spin-echo (Ramsey) pure dephasing time in fields up to $B=100~\text{G}$. With direct noise spectroscopy, we further observe a transition from a $1/f$ to approximately Lorentzian frequency dependence below 10 Hz and a reduction of the noise above 1 MHz with increasing magnetic field. We suggest that these trends are qualitatively consistent with an increase of spin cluster sizes with magnetic field. These results should help to inform a complete microscopic theory of $1/f$ flux noise in superconducting circuits

Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex With Men

Background. This study estimated the number of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against human immunodeficiency virus (HIV) infection for men who have sex with men (MSM). Methods. Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and rectal mononuclear cells from an intensive pharmacokinetic study ("Cell-PrEP" [ preexposure prophylaxis]) of 30 days of daily TDF/FTC followed by 30 days off drug were evaluated. A regression formula for HIV risk reduction derived from PBMCs collected in the preexposure prophylaxis initiative study was used to calculate inferred risk reduction. The time required to reach steady state for TFV-DP in rectal mononuclear cells was also determined. Results. Twenty-one HIV-uninfected adults participated in Cell-PrEP. The inferred HIV risk reduction, based on PBMC TFV-DP concentration, reached 99% (95% confidence interval [CI], 69%-100%) after 5 daily doses, and remained >90% for 7 days after stopping drug from steady-state conditions. The proportion of participants reaching the 90% effective concentration (EC 90 ) was 77% after 5 doses and 89% after 7 doses. The percentage of steady state for natural log [TFV-DP] in rectal mononuclear cells was 88% (95% CI, 66%-94%) after 5 doses and 94% (95% CI, 78%-98%) after 7 doses. Conclusions. High PrEP activity for MSM was achieved by approximately 1 week of daily dosing. Although effective intracellular drug concentrations persist for several days after stopping PrEP, a reasonable recommendation is to continue PrEP dosing for 4 weeks after the last potential HIV exposure, similar to recommendations for postexposure prophylaxis

Development and Validation of an Assay for Quantifying Budesonide in Dried Blood Spots Collected from Extremely Low Gestational Age Neonates

Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of \u3c200 μL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography – tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations

Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex With Men

BackgroundThis study estimated the number of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against human immunodeficiency virus (HIV) infection for men who have sex with men (MSM).MethodsTenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and rectal mononuclear cells from an intensive pharmacokinetic study ("Cell-PrEP" [preexposure prophylaxis]) of 30 days of daily TDF/FTC followed by 30 days off drug were evaluated. A regression formula for HIV risk reduction derived from PBMCs collected in the preexposure prophylaxis initiative study was used to calculate inferred risk reduction. The time required to reach steady state for TFV-DP in rectal mononuclear cells was also determined.ResultsTwenty-one HIV-uninfected adults participated in Cell-PrEP. The inferred HIV risk reduction, based on PBMC TFV-DP concentration, reached 99% (95% confidence interval [CI], 69%-100%) after 5 daily doses, and remained >90% for 7 days after stopping drug from steady-state conditions. The proportion of participants reaching the 90% effective concentration (EC90) was 77% after 5 doses and 89% after 7 doses. The percentage of steady state for natural log [TFV-DP] in rectal mononuclear cells was 88% (95% CI, 66%-94%) after 5 doses and 94% (95% CI, 78%-98%) after 7 doses.ConclusionsHigh PrEP activity for MSM was achieved by approximately 1 week of daily dosing. Although effective intracellular drug concentrations persist for several days after stopping PrEP, a reasonable recommendation is to continue PrEP dosing for 4 weeks after the last potential HIV exposure, similar to recommendations for postexposure prophylaxis

On-Demand Directional Microwave Photon Emission Using Waveguide Quantum Electrodynamics

Routing quantum information between non-local computational nodes is a foundation for extensible networks of quantum processors. Quantum information transfer between arbitrary nodes is generally mediated either by photons that propagate between them, or by resonantly coupling nearby nodes. The utility is determined by the type of emitter, propagation channel, and receiver. Conventional approaches involving propagating microwave photons have limited fidelity due to photon loss and are often unidirectional, whereas architectures that use direct resonant coupling are bidirectional in principle, but can generally accommodate only a few local nodes. Here we demonstrate high-fidelity, on-demand, directional, microwave photon emission. We do this using an artificial molecule comprising two superconducting qubits strongly coupled to a bidirectional waveguide, effectively creating a chiral microwave waveguide. Quantum interference between the photon emission pathways from the molecule generates single photons that selectively propagate in a chosen direction. This circuit will also be capable of photon absorption, making it suitable for building interconnects within extensible quantum networks