Parametric, nonparametric and parametric modelling of a chaotic circuit time series

The determination of a differential equation underlying a measured time series is a frequently arising task in nonlinear time series analysis. In the validation of a proposed model one often faces the dilemma that it is hard to decide whether possible discrepancies between the time series and model output are caused by an inappropriate model or by bad estimates of parameters in a correct type of model, or both. We propose a combination of parametric modelling based on Bock's multiple shooting algorithm and nonparametric modelling based on optimal transformations as a strategy to test proposed models and if rejected suggest and test new ones. We exemplify this strategy on an experimental time series from a chaotic circuit where we obtain an extremely accurate reconstruction of the observed attractor.Comment: 19 pages, 8 Fig

Spin orbit effects in a GaAs quantum dot in a parallel magnetic field

We analyze the effects of spin-orbit coupling on fluctuations of the conductance of a quantum dot fabricated in a GaAs heterostructure. We argue that spin-orbit effects may become important in the presence of a large parallel magnetic field B_{||}, even if they are negligble for B_{||}=0. This should be manifest in the level repulsion of a closed dot, and in reduced conductance fluctuations in dots with a small number of open channels in each lead, for large B_{||}. Our picture is consistent with the experimental observations of Folk et al.Comment: 5 page

Probabilistic Atlas Based Segmentation Using Affine Moment Descriptors and Graph-Cuts

We show a procedure for constructing a probabilistic atlas based on affine moment descriptors. It uses a normalization procedure over the labeled atlas. The proposed linear registration is defined by closed-form expressions involving only geometric moments. This procedure applies both to atlas construction as atlas-based segmentation. We model the likelihood term for each voxel and each label using parametric or nonparametric distributions and the prior term is determined by applying the vote-rule. The probabilistic atlas is built with the variability of our linear registration. We have two segmentation strategy: a) it applies the proposed affine registration to bring the target image into the coordinate frame of the atlas or b) the probabilistic atlas is non-rigidly aligning with the target image, where the probabilistic atlas is previously aligned to the target image with our affine registration. Finally, we adopt a graph cut - Bayesian framework for implementing the atlas-based segmentation

Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy

Exome sequencing revealed a homozygous missense mutation (c.317C>G [p.Arg106Pro]) in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations (c.199_201del [p.G1n67del] and c.810+1G>T) in an unrelated person with cone-rod dystrophy. Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.G1n67del variant forms of POC1B. Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments. These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs. Yeast two-hybrid screening of a human retinal cDNA library revealed FAM161A as a binary interaction partner of POC1B. This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.G1n67del variant forms of POC1B. FAM161A was previously implicated in autosomal-recessive retinitis pigmentosa and shown to be located at the base of the photoreceptor connecting cilium, where it interacts with several other ciliopathy-associated proteins. Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors

Experimental research: problems and opportunities in the big-data era

Experimental research in psychology, psycholinguistics or medicine provides quantitative and therefore seemingly conclusive and trustworthy evidence. However, it has been convincingly shown that most research findings are actually false. This has hardly influenced the dominant scientific evaluation system which reflects a continued trust in the unbiasedness of data by a strong reliance on simple quantifications of scientific quality and productivity, such as number of publications and number of citations. This state of affairs is remarkable in the light of a long history of strong criticism of commonly used inference methods and scientific evaluation systems, which is now backed by large-scale research projects directly questioning the reproducibility of scientific findings. This way, the large amounts of data – “big-data” – have helped to uncover some of these problematic issues, but also provided a more open attitude towards data and code sharing. In addition, novel analytic frameworks may help to better integrate empirical data with computational models

Quantum Pumping and Quantized Magnetoresistance in a Hall Bar

We show how a dc current can be generated in a Hall bar without applying a bias voltage. The Hall resistance $R_H$ that corresponds to this pumped current is quantized, just as in the usual integer quantum Hall effect (IQHE). In contrast with the IQHE, however, the longitudinal resistance $R_{xx}$ does not vanish on the plateaus, but equals the Hall resistance. We propose an experimental geometry to measure the pumped current and verify the predicted behavior of $R_H$ and $R_{xx}$.Comment: RevTeX, 3 figure

Weak localization and conductance fluctuations of a chaotic quantum dot with tunable spin-orbit coupling

In a two-dimensional quantum dot in a GaAs heterostructure, the spin-orbit scattering rate is substantially reduced below the rate in a bulk two-dimensional electron gas [B.I. Halperin et al, Phys. Rev. Lett. 86, 2106 (2001)]. Such a reduction can be undone if the spin-orbit coupling parameters acquire a spatial dependence, which can be achieved, e.g., by a metal gate covering only a part of the quantum dot. We calculate the effect of such spatially non-uniform spin-orbit scattering on the weak localization correction and the universal conductance fluctuations of a chaotic quantum dot coupled to electron reservoirs by ballistic point contacts, in the presence of a magnetic field parallel to the plane of the quantum dot.Comment: 4 pages, RevTeX; 2 figures. Substantial revision

Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics

BACKGROUND: Clozapine is highly effective in treatment-resistant schizophrenia, although, there remains significant variability in the response to this drug. To better understand this variability, the objective of this study was to predict brain extracellular fluid (ECF) concentrations and receptor occupancy of clozapine and norclozapine in human central nervous system by translating plasma and brain ECF pharmacokinetic (PK) relationships in the rat and coupling these with known human disposition of clozapine in the plasma. METHODS: Unbound concentrations of clozapine and norclozapine were measured in rat brain ECF using quantitative microdialysis after subcutaneous administration of a 10 mg/kg single dose of clozapine or norclozapine. These data were linked with plasma concentrations obtained in the same rats to develop a plasma-brain ECF compartmental model. Parameters describing brain ECF disposition were then allometrically scaled and linked with published human plasma PK to predict human ECF concentrations. Subsequently, prediction of human receptor occupancy at several CNS receptors was based on an effect model that related the predicted ECF concentrations to published concentration-driven receptor occupancy parameters. RESULTS: A one compartment model with first order absorption and elimination best described clozapine and norclozapine plasma concentrations in rats. A delay in the transfer of clozapine and norclozapine from plasma to the brain ECF compartment was captured using a transit compartment model approach. Human clozapine and norclozapine concentrations in brain ECF were simulated, and from these the median percentage of receptor occupancy of dopamine-2, serotonin-2A, muscarinic-1, alpha-1 adrenergic, alpha-2 adrenergic and histamine-1 for clozapine, and dopamine-2 for norclozapine were consistent with values reported in the literature. CONCLUSIONS: A PK model that relates clozapine and norclozapine disposition in rat plasma and brain, including blood-brain barrier transport, was developed. Using allometry and published human plasma PK, the model was successfully translated to predict clozapine and norclozapine concentrations and accordant receptor occupancy of both agents in human brain. These predicted exposure and occupancy measures at several receptors that bind clozapine may be employed to extend our understanding of clozapine's complex behavioral effects in humans