Bose-Einstein condensation in a circular waveguide

We have produced Bose-Einstein condensates in a ring-shaped magnetic waveguide. The few-millimeter diameter non-zero bias ring is formed from a time-averaged quadrupole ring. Condensates which propagate around the ring make several revolutions within the time it takes for them to expand to fill the ring. The ring shape is ideally suited for studies of vorticity in a multiply-connected geometry and is promising as a rotation sensor.Comment: 4 pages, 4 figure

On the phrasing properties of Hindi relative clauses

This paper presents results from a production experiment in Hindi, showing that differences in attachment site of object relative clauses result in prosodic differences when the antecedent of the relative clause (RC) is part of a complex NP with the structure N1 of N2. In particular, based on duration and F0 data we argue that the phrasing in a matrix sentence encodes the attachment site of the object RC. When the RC attaches high, i.e. modifying the head N1 of the complex NP, N2 and N1 form together a phonological phrase, while the verb of the matrix clause forms a phonological phrase on its own. In the case of low attachment, i.e. the RC modifies the genitive N2, the N2 forms its own phonological phrase, while N1 forms a phonological phrase with the verb of the matrix clause.Theoretical and Experimental Linguistic

Stochastic generation and suppression of early afterdepolarizations in a three-dimensional model of cardiac action potential

The influence of random disturbances on a three-dimensional simplification of Luo–Rudy model of the cardiac action potential is studied. We show that in the parameter region, where the deterministic model is in the equilibrium regime, noise can trigger large-amplitude oscillations that correspond with pathological early afterdepolarizations (EADs). For this stochastic excitement, the phenomenon of coherence resonance was discovered. On the contrary, in another parameter zone of the model, noise can suppress EADs. We analyze these stochastic phenomena using the stochastic sensitivity functions technique, Mahalanobis distance, the methods of principal directions, and confidence domains. © 2021 The Authors. Mathematical Methods in the Applied Sciences published by John Wiley & Sons, Ltd.Russian Science Foundation, RSF: 21-11-00062This work was supported by the Russian Science Foundation (No. 21-11-00062)

Bound States and Threshold Resonances in Quantum Wires with Circular Bends

We study the solutions to the wave equation in a two-dimensional tube of unit width comprised of two straight regions connected by a region of constant curvature. We introduce a numerical method which permits high accuracy at high curvature. We determine the bound state energies as well as the transmission and reflection matrices, ${\cal T}$ and ${\cal R}$ and focus on the nature of the resonances which occur in the vicinity of channel thresholds. We explore the dependence of these solutions on the curvature of the tube and angle of the bend and discuss several limiting cases where our numerical results confirm analytic predictions.Comment: 24 pages, revtex file, one style file and 17 PostScript figures include

Correlation between human ether-a-go-go-related gene channel inhibition and action potential prolongation

Background and Purpose: Human ether-a-go-go-related gene (hERG; Kv11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro-arrhythmic drug effects. This study used a library of dofetilide derivatives to investigate the relationship between standard measures of hERG current block in an expression system and changes in action potential duration (APD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The interference from accompanying block of Cav1.2 and Nav1.5 channels was investigated along with an in silico AP model. Experimental Approach: Drug-induced changes in APD were assessed in hiPSC-CMs using voltage-sensitive dyes. The IC50 values for dofetilide and 13 derivatives on hERG current were estimated in an HEK293 expression system. The relative potency of each drug on APD was estimated by calculating the dose (D150) required to prolong the APD at 90% (APD90) repolarization by 50%. Key Results: The D150 in hiPSC-CMs was linearly correlated with IC50 of hERG current. In silico simulations supported this finding. Three derivatives inhibited hERG without prolonging APD, and these compounds also inhibited Cav1.2 and/or Nav1.5 in a channel state-dependent manner. Adding Cav1.2 and Nav1.2 block to the in silico model recapitulated the direction but not the extent of the APD change. Conclusions and Implications: Potency of hERG current inhibition correlates linearly with an index of APD in hiPSC-CMs. The compounds that do not correlate have additional effects including concomitant block of Cav1.2 and/or Nav1.5 channels. In silico simulations of hiPSC-CMs APs confirm the principle of the multiple ion channel effects

Magnetic trapping of ultracold neutrons

Three-dimensional magnetic confinement of neutrons is reported. Neutrons are loaded into an Ioffe-type superconducting magnetic trap through inelastic scattering of cold neutrons with 4He. Scattered neutrons with sufficiently low energy and in the appropriate spin state are confined by the magnetic field until they decay. The electron resulting from neutron decay produces scintillations in the liquid helium bath that results in a pulse of extreme ultraviolet light. This light is frequency downconverted to the visible and detected. Results are presented in which 500 +/- 155 neutrons are magnetically trapped in each loading cycle, consistent with theoretical predictions. The lifetime of the observed signal, 660 s +290/-170 s, is consistent with the neutron beta-decay lifetime.Comment: 17 pages, 18 figures, accepted for publication in Physical Review

Imaging cytoplasmic cAMP in mouse brainstem neurons

<p>Abstract</p> <p>Background</p> <p>cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca²⁺levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.</p> <p>Results</p> <p>Using a strictly neuron-restricted promoter we virally transduced neurons in the organotypic brainstem slices which contained pre-Bötzinger complex, constituting the rhythm-generating part of the respiratory network. Fluorescent cAMP sensor Epac1-camps was expressed both in neuronal cell bodies and neurites, allowing us to measure intracellular distribution of cAMP, its absolute levels and time-dependent changes in response to physiological stimuli. We recorded [cAMP]_ichanges in the micromolar range after modulation of adenylate cyclase, inhibition of phosphodiesterase and activation of G-protein-coupled metabotropic receptors. [cAMP]_ilevels increased after membrane depolarisation and release of Ca²⁺from internal stores. The effects developed slowly and reached their maximum after transient [Ca²⁺]_ielevations subsided. Ca²⁺-dependent [cAMP]_itransients were suppressed after blockade of adenylate cyclase with 0.1 mM adenylate cyclase inhibitor 2'5'-dideoxyadenosine and potentiated after inhibiting phosphodiesterase with isobutylmethylxanthine and rolipram. During paired stimulations, the second depolarisation and Ca²⁺release evoked bigger cAMP responses. These effects were abolished after inhibition of protein kinase A with H-89 pointing to the important role of phosphorylation of calcium channels in the potentiation of [cAMP]_itransients.</p> <p>Conclusion</p> <p>We constructed and characterized a neuron-specific cAMP probe based on Epac1-camps. Using viral gene transfer we showed its efficient expression in organotypic brainstem preparations. Strong fluorescence, resistance to photobleaching and possibility of direct estimation of [cAMP] levels using dual wavelength measurements make the probe useful in studies of neurons and the mechanisms of their plasticity. Epac1-camps was applied to examine the crosstalk between Ca²⁺and cAMP signalling and revealed a synergism of actions of these two second messengers.</p

miRNA Regulatory Circuits in ES Cells Differentiation: A Chemical Kinetics Modeling Approach

MicroRNAs (miRNAs) play an important role in gene regulation for Embryonic Stem cells (ES cells), where they either down-regulate target mRNA genes by degradation or repress protein expression of these mRNA genes by inhibiting translation. Well known tables TargetScan and miRanda may predict quite long lists of potential miRNAs inhibitors for each mRNA gene, and one of our goals was to strongly narrow down the list of mRNA targets potentially repressed by a known large list of 400 miRNAs. Our paper focuses on algorithmic analysis of ES cells microarray data to reliably detect repressive interactions between miRNAs and mRNAs. We model, by chemical kinetics equations, the interaction architectures implementing the two basic silencing processes of miRNAs, namely “direct degradation” or “translation inhibition” of targeted mRNAs. For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data. When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction. This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation

CerebNet: A fast and reliable deep-learning pipeline for detailed cerebellum sub-segmentation

Quantifying the volume of the cerebellum and its lobes is of profound interest in various neurodegenerative and acquired diseases. Especially for the most common spinocerebellar ataxias (SCA), for which the first antisense oligonculeotide-base gene silencing trial has recently started, there is an urgent need for quantitative, sensitive imaging markers at pre-symptomatic stages for stratification and treatment assessment. This work introduces CerebNet, a fully automated, extensively validated, deep learning method for the lobular segmentation of the cerebellum, including the separation of gray and white matter. For training, validation, and testing, T1-weighted images from 30 participants were manually annotated into cerebellar lobules and vermal sub-segments, as well as cerebellar white matter. CerebNet combines FastSurferCNN, a UNet-based 2.5D segmentation network, with extensive data augmentation, e.g. realistic non-linear deformations to increase the anatomical variety, eliminating additional preprocessing steps, such as spatial normalization or bias field correction. CerebNet demonstrates a high accuracy (on average 0.87 Dice and 1.742mm Robust Hausdorff Distance across all structures) outperforming state-of-the-art approaches. Furthermore, it shows high test-retest reliability (average ICC >0.97 on OASIS and Kirby) as well as high sensitivity to disease effects, including the pre-ataxic stage of spinocerebellar ataxia type 3 (SCA3). CerebNet is compatible with FreeSurfer and FastSurfer and can analyze a 3D volume within seconds on a consumer GPU in an end-to-end fashion, thus providing an efficient and validated solution for assessing cerebellum sub-structure volumes. We make CerebNet available as source-code (https://github.com/Deep-MI/FastSurfer)