Room-Temperature Ferrimagnet with Frustrated Antiferroelectricity: Promising Candidate Toward Multiple State Memory

On the basis of first-principles calculations we show that the M-type hexaferrite BaFe12O19 exhibits frustrated antiferroelectricity associated with its trigonal bipyramidal Fe3+ sites. The ferroelectric (FE) state of BaFe12O19, reachable by applying an external electric field to the antiferroelectric (AFE) state, can be made stable at room temperature by appropriate element substitution or strain engineering. Thus M-type hexaferrite, as a new type of multiferoic with coexistence of antiferroelectricity and ferrimagnetism, provide a basis for studying the phenomenon of frustrated antiferroelectricity and realizing multiple state memory devices.Comment: supporting material available via email. arXiv admin note: text overlap with arXiv:1210.7116 by other author

Topological energy bounds in generalized Skyrme models

The Skyrme model has a natural generalization amenable to a standard hamiltonian treatment, consisting of the standard sigma model and the Skyrme terms, a potential, and a certain term sextic in first derivatives. Here we demonstrate that, in this theory, each pair of terms in the static energy functional which may support topological solitons according to the Derrick criterion (i.e., each pair of terms with opposite Derrick scaling) separately posesses a topological energy bound. As a consequence, there exists a four-parameter family of topological bounds for the full generalized Skyrme model. The optimal bounds, i.e., the optimal values of the parameters, depend both on the form of the potential and on the relative strength of the different terms. It also follows that various submodels of the generalized Skyrme model have one-parameter families of topological energy bounds. We also consider the case of topological bounds for the generalized Skyrme model on a compact base space as well as generalizations to higher dimensions.Comment: Latex, 26 pages, version accepted for publication in PRD, presentation and motivation slightly changed, references added, results unchange

The standards process: Technical committee X3B5 digital magnetic tape

The definition of X3B5, where it fits in the national and international standards development process, and how it interfaces and influences the world community of standards developers are provided. Details concerning the focus of the committee, how it operates, and what the group sees as the future trends in the area of interchange standards utilizing the multifaceted, ubiquitous magnetic tape are presented

Representing and Utilizing DDI in Relational Databases

This document is primarily intended for implementers of DDI-based metadata stores who are considering different technical options for housing and managing their metadata. The Data Documentation Initiative (DDI) metadata specification is expressed in the form of XML schema. With version 3, the DDI specification has become quite complex, including 21 namespaces and 846 elements. Organizations employing DDI, or considering doing so, may want to 1. store and manage the metadata elements in relational databases, for reasons of integration with existing systems, familiarity with the concepts of relational databases (such as Structured Query Language), systems performance, and/or other reasons; 2. select only the subset of the available DDI metadata elements that is of utility to their work, and have the flexibility of capturing metadata they need that would not fit into the DDI model. This paper discusses advantages and disadvantages of the relational database approach to managing DDI. It also describes methods for modeling DDI in relational databases and for formally defining subsets of DDI to employ in this environment.

Feynman's Diagrams, Pictorial Representations and Styles of Scientific Thinking

In this paper we argue that the different positions taken by Dyson and Feynman on Feynman diagrams’ representational role depend on different styles of scientific thinking. We begin by criticizing the idea that Feynman Diagrams can be considered to be pictures or depictions of actual physical processes. We then show that the best interpretation of the role they play in quantum field theory and quantum electrodynamics is captured by Hughes' Denotation, Deduction and Interpretation theory of models (DDI), where “models” are to be interpreted as inferential, non-representational devices constructed in given social contexts by the community of physicists

The nature of representation in Feynman diagrams

After a brief presentation of Feynman diagrams, we criticizise the idea that Feynman diagrams can be considered to be pictures or depictions of actual physical processes. We then show that the best interpretation of the role they play in quantum field theory and quantum electrodynamics is captured by Hughes' Denotation, Deduction and Interpretation theory of models (DDI), where models are to be interpreted as inferential, non-representational devices constructed in given social contexts by the community of physicists

The role of interaction model in simulation of drug interactions and QT prolongation

Computational modelling is a cornerstone of Comprehensive In Vitro Proarrhythmia Assay and is re-increasingly being used in drug development. Electrophysiological effects of drug-drug interactions can be predicted in silico, e.g. with the use of in vitro cardiac ion channel data, PK profiles and human ventricular cardiomyocyte models. There are, however, several approaches with different assumptions used to assess the combined effect of multiple drugs, and there is no agreed standard interaction model. The aim of this study was to assess whether the choice of the drug-drug interaction (DDI) model (Bliss independence, Loewe additivity, or simple sum) influences the results of QT interval simulation trial. The Simcyp Simulator version 12.1 (Simcyp Ltd. [part of Certara], Sheffield, UK) and Cardiac Safety Simulator 2.0 (Simcyp Ltd. [part of Certara], Sheffield, UK) were used to simulate results of 8 virtual trials mimicking clinical studies and generate individual QTc data. The combined effect of inhibitory actions of drugs which were given simultaneously was calculated with use of three different interaction models. The PD effect of DDI was assessed and the differences between mean observed and mean predicted ΔQTcB values for terfenadine interactions were not statistically significant in all but one cases. Differences between the three DDI models are not statistically significant, implying that the choice of the DDI model, in the case of lack of synergy or antagonism, is irrelevant to the average predicted effect at the clinical level. However, in some cases, it can influence the verdict on combinatorial therapy safety for individual patients

Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers

Low-dose oral S-ketamine is increasingly used in chronic pain therapy, but extensive cytochrome P450 (CYP) mediated metabolism makes it prone to pharmacokinetic drug-drug interactions (DDIs). In our study, concentration-time data from five studies were used to develop a semimechanistic model that describes the ticlopidine-mediated inhibition of S-ketamine biotransformation. A mechanistic model was implemented to account for reversible and time-dependent hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S-ketamine exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic clearances for S-ketamine, its primary metabolite norketamine, and ticlopidine. Nonlinear mixed effects modeling approach was used (NONMEM version 7.3.0), and the final model was evaluated with visual predictive checks and the sampling-importance-resampling procedure. Our final model produces biologically plausible output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated S-ketamine metabolism. Simulations from our model may be used to evaluate chronic pain therapy with S-ketamine.Peer reviewe

Distributed Dendritic Processing Facilitates Object Detection: A Computational Analysis on the Visual System of the Fly

Hennig P, Möller R, Egelhaaf M. Distributed Dendritic Processing Facilitates Object Detection: A Computational Analysis on the Visual System of the Fly. PLoS ONE. 2008;3(8): e3092.Background: Detecting objects is an important task when moving through a natural environment. Flies, for example, may land on salient objects or may avoid collisions with them. The neuronal ensemble of Figure Detection cells (FD-cells) in the visual system of the fly is likely to be involved in controlling these behaviours, as these cells are more sensitive to objects than to extended background structures. Until now the computations in the presynaptic neuronal network of FD-cells and, in particular, the functional significance of the experimentally established distributed dendritic processing of excitatory and inhibitory inputs is not understood. Methodology/Principal Findings: We use model simulations to analyse the neuronal computations responsible for the preference of FD-cells for small objects. We employed a new modelling approach which allowed us to account for the spatial spread of electrical signals in the dendrites while avoiding detailed compartmental modelling. The models are based on available physiological and anatomical data. Three models were tested each implementing an inhibitory neural circuit, but differing by the spatial arrangement of the inhibitory interaction. Parameter optimisation with an evolutionary algorithm revealed that only distributed dendritic processing satisfies the constraints arising from electrophysiological experiments. In contrast to a direct dendro-dendritic inhibition of the FD-cell (Direct Distributed Inhibition model), an inhibition of its presynaptic retinotopic elements (Indirect Distributed Inhibition model) requires smaller changes in input resistance in the inhibited neurons during visual stimulation. Conclusions/Significance: Distributed dendritic inhibition of retinotopic elements as implemented in our Indirect Distributed Inhibition model is the most plausible wiring scheme for the neuronal circuit of FD-cells. This microcircuit is computationally similar to lateral inhibition between the retinotopic elements. Hence, distributed inhibition might be an alternative explanation of perceptual phenomena currently explained by lateral inhibition networks

A Physiologically Based Pharmacokinetic Model of Ketoconazole and Its Metabolites as Drug–Drug Interaction Perpetrators

The antifungal ketoconazole, which is mainly used for dermal infections and treatment of Cushing’s syndrome, is prone to drug–food interactions (DFIs) and is well known for its strong drug– drug interaction (DDI) potential. Some of ketoconazole’s potent inhibitory activity can be attributed to its metabolites that predominantly accumulate in the liver. This work aimed to develop a wholebody physiologically based pharmacokinetic (PBPK) model of ketoconazole and its metabolites for fasted and fed states and to investigate the impact of ketoconazole’s metabolites on its DDI potential. The parent–metabolites model was developed with PK-Sim® and MoBi® using 53 plasma concentration-time profiles. With 7 out of 7 (7/7) DFI AUClast and DFI Cmax ratios within two-fold of observed ratios, the developed model demonstrated good predictive performance under fasted and fed conditions. DDI scenarios that included either the parent alone or with its metabolites were simulated and evaluated for the victim drugs alfentanil, alprazolam, midazolam, triazolam, and digoxin. DDI scenarios that included all metabolites as reversible inhibitors of CYP3A4 and P-gp performed best: 26/27 of DDI AUClast and 21/21 DDI Cmax ratios were within two-fold of observed ratios, while DDI models that simulated only ketoconazole as the perpetrator underperformed: 12/27 DDI AUClast and 18/21 DDI Cmax ratios were within the success limits