Role of Quasiparticles in an Electric Circuit with Josephson Junctions.

Although Josephson junctions can be viewed as highly nonlinear impedances for superconducting quantum technologies, they also possess internal dynamics that may strongly affect their behavior. Here, we construct a computational framework that includes a microscopic description of the junction (full fledged treatment of both the superconducting condensate and the quasiparticles) in the presence of a surrounding electrical circuit. Our approach generalizes the standard resistor capacitor Josephson model to arbitrary junctions (including, e.g., multiterminal geometries and/or junctions that embed topological or magnetic elements) and arbitrary electric circuits treated at the classical level. By treating the superconducting condensate and quasiparticles on equal footings, we capture nonequilibrium phenomena such as multiple Andreev reflection. We show that the interplay between the quasiparticle dynamics and the electrical environment leads to the emergence of new phenomena. In a RC circuit connected to single channel Josephson junction, we find out-of-equilibrium current-phase relations that are strongly distorted with respect to the (almost sinusoidal) equilibrium one, revealing the presence of the high harmonic ac Josephson effect. In an RLC circuit connected to a junction, we find that the shape of the resonance is strongly modified by the quasiparticle dynamics: close to resonance, the current can be smaller than without the resonator. Our approach provides a route for the quantitative modeling of superconducting-based circuits.

Smart Medical Information Technology for Healthcare (SMITH).

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on the German Medical Informatics Initiative. "Smart Medical Information Technology for Healthcare (SMITH)" is one of four consortia funded by the German Medical Informatics Initiative (MI-I) to create an alliance of universities, university hospitals, research institutions and IT companies. SMITH's goals are to establish Data Integration Centers (DICs) at each SMITH partner hospital and to implement use cases which demonstrate the usefulness of the approach. OBJECTIVES: To give insight into architectural design issues underlying SMITH data integration and to introduce the use cases to be implemented. GOVERNANCE AND POLICIES: SMITH implements a federated approach as well for its governance structure as for its information system architecture. SMITH has designed a generic concept for its data integration centers. They share identical services and functionalities to take best advantage of the interoperability architectures and of the data use and access process planned. The DICs provide access to the local hospitals' Electronic Medical Records (EMR). This is based on data trustee and privacy management services. DIC staff will curate and amend EMR data in the Health Data Storage. METHODOLOGY AND ARCHITECTURAL FRAMEWORK: To share medical and research data, SMITH's information system is based on communication and storage standards. We use the Reference Model of the Open Archival Information System and will consistently implement profiles of Integrating the Health Care Enterprise (IHE) and Health Level Seven (HL7) standards. Standard terminologies will be applied. The SMITH Market Place will be used for devising agreements on data access and distribution. 3LGM2 for enterprise architecture modeling supports a consistent development process.The DIC reference architecture determines the services, applications and the standardsbased communication links needed for efficiently supporting the ingesting, data nourishing, trustee, privacy management and data transfer tasks of the SMITH DICs. The reference architecture is adopted at the local sites. Data sharing services and the market place enable interoperability. USE CASES: The methodological use case "Phenotype Pipeline" (PheP) constructs algorithms for annotations and analyses of patient-related phenotypes according to classification rules or statistical models based on structured data. Unstructured textual data will be subject to natural language processing to permit integration into the phenotyping algorithms. The clinical use case "Algorithmic Surveillance of ICU Patients" (ASIC) focusses on patients in Intensive Care Units (ICU) with the acute respiratory distress syndrome (ARDS). A model-based decision-support system will give advice for mechanical ventilation. The clinical use case HELP develops a "hospital-wide electronic medical record-based computerized decision support system to improve outcomes of patients with blood-stream infections" (HELP). ASIC and HELP use the PheP. The clinical benefit of the use cases ASIC and HELP will be demonstrated in a change of care clinical trial based on a step wedge design. DISCUSSION: SMITH's strength is the modular, reusable IT architecture based on interoperability standards, the integration of the hospitals' information management departments and the public-private partnership. The project aims at sustainability beyond the first 4-year funding period.

Unveiling the bosonic nature of an ultrashort few-electron pulse.

Quantum dynamics is very sensitive to dimensionality. While two-dimensional electronic systems form Fermi liquids, one-dimensional systems-Tomonaga-Luttinger liquids-are described by purely bosonic excitations, even though they are initially made of fermions. With the advent of coherent single-electron sources, the quantum dynamics of such a liquid is now accessible at the single-electron level. Here, we report on time-of-flight measurements of ultrashort few-electron charge pulses injected into a quasi one-dimensional quantum conductor. By changing the confinement potential we can tune the system from the one-dimensional Tomonaga-Luttinger liquid limit to the multi-channel Fermi liquid and show that the plasmon velocity can be varied over almost an order of magnitude. These results are in quantitative agreement with a parameter-free theory and demonstrate a powerful probe for directly investigating real-time dynamics of fractionalisation phenomena in low-dimensional conductors.

Kardar-Parisi-Zhang equation with short-range correlated noise: Emergent symmetries and nonuniversal observables.

We investigate the stationary-state fluctuations of a growing one-dimensional interface described by the Kardar-Parisi-Zhang (KPZ) dynamics with a noise featuring smooth spatial correlations of characteristic range ξ. We employ nonperturbative functional renormalization group methods to resolve the properties of the system at all scales. We show that the physics of the standard (uncorrelated) KPZ equation emerges on large scales independently of ξ. Moreover, the renormalization group flow is followed from the initial condition to the fixed point, that is, from the microscopic dynamics to the large-distance properties. This provides access to the small-scale features (and their dependence on the details of the noise correlations) as well as to the universal large-scale physics. In particular, we compute the kinetic energy spectrum of the stationary state as well as its nonuniversal amplitude. The latter is experimentally accessible by measurements at large scales and retains a signature of the microscopic noise correlations. Our results are compared to previous analytical and numerical results from independent approaches. They are in agreement with direct numerical simulations for the kinetic energy spectrum as well as with the prediction, obtained with the replica trick by Gaussian variational method, of a crossover in ξ of the nonuniversal amplitude of this spectrum.

The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies, aqueous pK a, and cyclohexane-water log D.

We predict cyclohexane-water distribution coefficients (log D 7.4) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the "embedded cluster reference interaction site model" (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (pK a) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the "Minnesota Solvation Database" (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol-1 for water and 0.8-0.9 kcal mol-1 for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical pK a model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2-3 for each solvent and two for the pK a) for training solvation and acidity models. Applying the final models to the log D 7.4 dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0-2.1 for the RMSE with the first and 2.2-2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed.

Kardar-Parisi-Zhang equation with spatially correlated noise: a unified picture from nonperturbative renormalization group.

We investigate the scaling regimes of the Kardar-Parisi-Zhang (KPZ) equation in the presence of spatially correlated noise with power-law decay D(p) ∼ p(-2ρ) in Fourier space, using a nonperturbative renormalization group approach. We determine the full phase diagram of the system as a function of ρ and the dimension d. In addition to the weak-coupling part of the diagram, which agrees with the results from Europhys. Lett. 47, 14 (1999) and Eur. Phys. J. B 9, 491 (1999), we find the two fixed points describing the short-range- (SR) and long-range- (LR) dominated strong-coupling phases. In contrast with a suggestion in the references cited above, we show that, for all values of ρ, there exists a unique strong-coupling SR fixed point that can be continuously followed as a function of d. We show in particular that the existence and the behavior of the LR fixed point do not provide any hint for 4 being the upper critical dimension of the KPZ equation with SR noise.

Strong-coupling phases of the anisotropic Kardar-Parisi-Zhang equation.

We study the anisotropic Kardar-Parisi-Zhang equation using nonperturbative renormalization group methods. In contrast to a previous analysis in the weak-coupling regime, we find the strong-coupling fixed point corresponding to the isotropic rough phase to be always locally stable and unaffected by the anisotropy even at noninteger dimensions. Apart from the well-known weak-coupling and the now well-established isotropic strong-coupling behavior, we find an anisotropic strong-coupling fixed point for nonlinear couplings of opposite signs at noninteger dimensions.

Nonperturbative renormalization group for the stationary Kardar-Parisi-Zhang equation: scaling functions and amplitude ratios in 1+1, 2+1, and 3+1 dimensions.

We investigate the strong-coupling regime of the stationary Kardar-Parisi-Zhang equation for interfaces growing on a substrate of dimension d = 1, 2, and 3 using a nonperturbative renormalization group (NPRG) approach. We compute critical exponents, correlation and response functions, extract the related scaling functions, and calculate universal amplitude ratios. We work with a simplified implementation of the second-order (in the response field) approximation proposed in a previous work [Phys. Rev. E 84, 061150 (2011) and Phys. Rev. E 86, 019904(E) (2012)], which greatly simplifies the frequency sector of the NPRG flow equations, while keeping a nontrivial frequency dependence for the two-point functions. The one-dimensional scaling function obtained within this approach compares very accurately with the scaling function obtained from the full second-order NPRG equations and with the exact scaling function. Furthermore, the approach is easily applicable to higher dimensions and we provide scaling functions and amplitude ratios in d = 2 and d = 3. We argue that our ansatz is reliable up to d [Symbol: see text] 3.5.

Salt bridges in the miniature viral channel Kcv are important for function.

The viral potassium channel Kcv comprises only 94 amino acids, which represent the pore module of more complex K(+) channels. As for Kir-type channels, Kcv also has a short N-terminal helix exposed to the cytoplasm, upstream of the first transmembrane domain. Here we show that this helix is relevant for Kcv function. The presence of charged amino acids, which form dynamic inter- and intra-subunit salt bridges is crucial. Electrophysiological measurements, yeast rescue experiments and molecular dynamics simulations show that mutants in which the critical salt bridge formation is impaired have no or reduced channel activity. We conclude that these salt bridges destabilise the complexation of K(+) ions by negative charges on the inner transmembrane domain at the entrance into the cavity. This feature facilitates a continuous and coordinated transfer of ions between the cavity and the cytoplasm for channels without the canonical bundle crossing.

Model development for the viral Kcv potassium channel.

A computational model for the open state of the short viral Kcv potassium channel was created and tested based on homology modeling and extensive molecular-dynamics simulation in a membrane environment. Particular attention was paid to the structure of the highly flexible N-terminal region and to the protonation state of membrane-exposed lysine residues. Data from various experimental sources, NMR spectroscopy, and electrophysiology, as well as results from three-dimensional reference interaction site model integral equation theory were taken into account to select the most reasonable model among possible variants. The final model exhibits spontaneous ion transitions across the complete pore, with and without application of an external field. The nonequilibrium transport events could be induced reproducibly without abnormally large driving potential and without the need to place ions artificially at certain key positions along the transition path. The transport mechanism through the filter region corresponds to the classic view of single-file motion, which in our case is coupled to frequent exchange of ions between the innermost filter position and the cavity.

Treatment of charged solutes in three-dimensional integral equation theory.

Periodicity artifacts, which occur within three-dimensional reference interaction site model integral equation theory for net-charged solute systems, are analyzed and corrected by means of a renormalization procedure for long range interactions. The method is formulated for solute-solvent and solute-solute variants of the theory. Both dielectric and electrolyte solvents are considered. Comparison of the results for atomic ions with one-dimensional reference computations shows that structural and thermodynamic artifacts are efficiently removed.

Quantum chemistry in solution by combining 3D integral equation theory with a cluster embedding approach.

Free energy changes associated with chemical reactions in solution are treated by integral equation theory in the form of the 3D reference interaction site model (RISM) in combination with quantum-chemical calculations via an embedded cluster approach (EC-RISM). The electronic structure of the solute is computed self-consistently with the solvent structure by mapping the charge distribution of the solvent onto a set of discrete background point charges that are added to the molecular Hamiltonian. The EC-RISM procedure yields chemical accuracy in free energy predictions for several benchmark systems without adjusting empirical parameters. We apply the method to the standard reaction free energy for the gauche-trans equilibrium of 1,2-dichloroethane in water and to pKa shift calculations for trifluoroacetic acid/acetic acid and 4-nitroaniline/aniline in water.

Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine predict adverse events in patients undergoing noncardiac surgery.

OBJECTIVE: In patients with cardiovascular disease or organ failure, elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are associated with an increased risk of future cardiovascular events. We aimed to investigate elevated plasma ADMA concentrations as a prospective risk marker for adverse events in patients undergoing noncardiac surgery. DESIGN: Prospective observational study. SETTING: Two tertiary care centers. PATIENTS: Four hundred and two patients scheduled for elective noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed for 30 days after surgery for a predefined composite end point (death, myocardial infarction/acute coronary syndrome, acute heart failure, severe arrhythmia, embolism, or thrombosis). Plasma ADMA concentrations at baseline were determined by high-performance liquid chromatography. ADMA was only weakly (-0.2 < tau < 0.2) correlated with other risk markers and risk scores. In univariate logistic regression, per 0.1-micromol/L increment in plasma ADMA concentration, the odds ratio to experience the primary end point increased by 1.26 (95% confidence interval 1.10-1.45, p = .001). In a multivariate logistic regression model adjusting for age, gender, current smoking, plasma creatinine, hypertension, diabetes, ischemic heart disease, highly sensitive C-reactive protein, revised cardiac risk index, type of surgery, high-risk surgery, ASA class, and study center, ADMA was found to be an independent risk marker. The odds ratio to experience the primary end point was 1.33 (95% confidence interval 1.12-1.59, p = .001) per 0.1-micromol/L increase in the plasma ADMA concentration. CONCLUSIONS: Elevated plasma ADMA concentrations are independently associated with a higher risk for adverse events in the peri- and postoperative periods.

Molecular dynamics simulation of the cytosolic mouth in Kcv-type potassium channels.

The functional effect of mutations near the intracellular mouth of the short viral Kcv potassium channel was studied by molecular dynamics simulations. As a model system we used the analogously mutated and truncated KirBac1.1, a channel with known crystal structure that shares genuine local sequence motifs with Kcv. By a novel simulated annealing methodology for structural averaging, information about the structure and dynamics of the intracellular mouth was extracted and complemented by Poisson-Boltzmann and 3D-RISM (reference interaction site model) integral equation theory for the determination of the K+ free energy surface. Besides the wild-type analogue of Kcv with its experimental reference activity (truncated KirBac1.1), two variants were studied: a deletion mutant where the N-terminus is further truncated by eight amino acids, showing inactivity in the Kcv reference system, and a point mutant where the kink-forming proline at position 13 is substituted by alanine, resulting in hyperactivity. The computations reveal that the change of activity is closely related to a hydrophilic intracellular constriction formed by the C-terminal residues of the monomers. Hyperactivity of the point mutant is correlated with both sterical and electrostatic factors, while inactivity of the deletion mutant is related to a loss of specific salt bridge patterns between the C- and N-terminus at the constriction and to the consequences for ion passage barriers, as revealed by integral equation theory. The cytosolic gate, however, is probably formed by the N-terminal segment up to the proline kink and not by the constriction. The results are compared with design principles found for other channels.