On the Interface Formation Model for Dynamic Triple Lines

This paper revisits the theory of Y. Shikhmurzaev on forming interfaces as a continuum thermodynamical model for dynamic triple lines. We start with the derivation of the balances for mass, momentum, energy and entropy in a three-phase fluid system with full interfacial physics, including a brief review of the relevant transport theorems on interfaces and triple lines. Employing the entropy principle in the form given in [Bothe & Dreyer, Acta Mechanica, doi:10.1007/s00707-014-1275-1] but extended to this more general case, we arrive at the entropy production and perform a linear closure, except for a nonlinear closure for the sorption processes. Specialized to the isothermal case, we obtain a thermodynamically consistent mathematical model for dynamic triple lines and show that the total available energy is a strict Lyapunov function for this system

Disjoining Potential and Spreading of Thin Liquid Layers in the Diffuse Interface Model Coupled to Hydrodynamics

The hydrodynamic phase field model is applied to the problem of film spreading on a solid surface. The disjoining potential, responsible for modification of the fluid properties near a three-phase contact line, is computed from the solvability conditions of the density field equation with appropriate boundary conditions imposed on the solid support. The equation describing the motion of a spreading film are derived in the lubrication approximation. In the case of quasi-equilibrium spreading, is shown that the correct sharp-interface limit is obtained, and sample solutions are obtained by numerical integration. It is further shown that evaporation or condensation may strongly affect the dynamics near the contact line, and accounting for kinetic retardation of the interphase transport is necessary to build up a consistent theory.Comment: 14 pages, 5 figures, to appear in PR

High-finesse Fabry-Perot cavities with bidimensional Si3_3N4_4 photonic-crystal slabs

Light scattering by a two-dimensional photonic crystal slab (PCS) can result in dramatic interference effects associated with Fano resonances. Such devices offer appealing alternatives to distributed Bragg reflectors or filters for various applications such as optical wavelength and polarization filters, reflectors, semiconductor lasers, photodetectors, bio-sensors, or non-linear optical components. Suspended PCSs also find natural applications in the field of optomechanics, where the mechanical modes of a suspended slab interact via radiation pressure with the optical field of a high finesse cavity. The reflectivity and transmission properties of a defect-free suspended PCS around normal incidence can be used to couple out-of-plane mechanical modes to an optical field by integrating it in a free space cavity. Here, we demonstrate the successful implementation of a PCS reflector on a high-tensile stress Si$_3$N$_4$ nanomembrane. We illustrate the physical process underlying the high reflectivity by measuring the photonic crystal band diagram. Moreover, we introduce a clear theoretical description of the membrane scattering properties in the presence of optical losses. By embedding the PCS inside a high-finesse cavity, we fully characterize its optical properties. The spectrally, angular, and polarization resolved measurements demonstrate the wide tunability of the membrane's reflectivity, from nearly 0 to 99.9470~$\pm$ 0.0025 \%, and show that material absorption is not the main source of optical loss. Moreover, the cavity storage time demonstrated in this work exceeds the mechanical period of low-order mechanical drum modes. This so-called resolved sideband condition is a prerequisite to achieve quantum control of the mechanical resonator with light

The use of the SAEM algorithm in MONOLIX software for estimation of population pharmacokinetic-pharmacodynamic-viral dynamics parameters of maraviroc in asymptomatic HIV subjects

Using simulated viral load data for a given maraviroc monotherapy study design, the feasibility of different algorithms to perform parameter estimation for a pharmacokinetic-pharmacodynamic-viral dynamics (PKPD-VD) model was assessed. The assessed algorithms are the first-order conditional estimation method with interaction (FOCEI) implemented in NONMEM VI and the SAEM algorithm implemented in MONOLIX version 2.4. Simulated data were also used to test if an effect compartment and/or a lag time could be distinguished to describe an observed delay in onset of viral inhibition using SAEM. The preferred model was then used to describe the observed maraviroc monotherapy plasma concentration and viral load data using SAEM. In this last step, three modelling approaches were compared; (i) sequential PKPD-VD with fixed individual Empirical Bayesian Estimates (EBE) for PK, (ii) sequential PKPD-VD with fixed population PK parameters and including concentrations, and (iii) simultaneous PKPD-VD. Using FOCEI, many convergence problems (56%) were experienced with fitting the sequential PKPD-VD model to the simulated data. For the sequential modelling approach, SAEM (with default settings) took less time to generate population and individual estimates including diagnostics than with FOCEI without diagnostics. For the given maraviroc monotherapy sampling design, it was difficult to separate the viral dynamics system delay from a pharmacokinetic distributional delay or delay due to receptor binding and subsequent cellular signalling. The preferred model included a viral load lag time without inter-individual variability. Parameter estimates from the SAEM analysis of observed data were comparable among the three modelling approaches. For the sequential methods, computation time is approximately 25% less when fixing individual EBE of PK parameters with omission of the concentration data compared with fixed population PK parameters and retention of concentration data in the PD-VD estimation step. Computation times were similar for the sequential method with fixed population PK parameters and the simultaneous PKPD-VD modelling approach. The current analysis demonstrated that the SAEM algorithm in MONOLIX is useful for fitting complex mechanistic models requiring multiple differential equations. The SAEM algorithm allowed simultaneous estimation of PKPD and viral dynamics parameters, as well as investigation of different model sub-components during the model building process. This was not possible with the FOCEI method (NONMEM version VI or below). SAEM provides a more feasible alternative to FOCEI when facing lengthy computation times and convergence problems with complex models

Emapalumab in children with primary hemophagocytic lymphohistiocytosis

Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P=0.02 and P=0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis

Emapalumab in children with primary hemophagocytic lymphohistiocytosis

Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality

High-sensitivity AC-charge detection with a MHz-frequency fluxonium qubit

Owing to their strong dipole moment and long coherence times, superconducting qubits have demonstrated remarkable success in hybrid quantum circuits. However, most qubit architectures are limited to the GHz frequency range, severely constraining the class of systems they can interact with. The fluxonium qubit, on the other hand, can be biased to very low frequency while being manipulated and read out with standard microwave techniques. Here, we design and operate a heavy fluxonium with an unprecedentedly low transition frequency of $1.8~\mathrm{MHz}$. We demonstrate resolved sideband cooling of the ``hot'' qubit transition with a final ground state population of $97.7~\%$, corresponding to an effective temperature of $23~\mu\mathrm{K}$. We further demonstrate coherent manipulation with coherence times $T_1=34~\mu\mathrm{s}$, $T_2^*=39~\mu\mathrm{s}$, and single-shot readout of the qubit state. Importantly, by directly addressing the qubit transition with a capacitively coupled waveguide, we showcase its high sensitivity to a radio-frequency field. Through cyclic qubit preparation and interrogation, we transform this low-frequency fluxonium qubit into a frequency-resolved charge sensor. This method results in a charge sensitivity of $33~\mu\mathrm{e}/\sqrt{\mathrm{Hz}}$, or an energy sensitivity (in joules per hertz) of $2.8~\hbar$. This method rivals state-of-the-art transport-based devices, while maintaining inherent insensitivity to DC charge noise. The high charge sensitivity combined with large capacitive shunt unlocks new avenues for exploring quantum phenomena in the $1-10~\mathrm{MHz}$ range, such as the strong-coupling regime with a resonant macroscopic mechanical resonator