Functional characterization of GABAA receptor-mediated modulation of cortical neuron network activity in microelectrode array recordings

The numerous γ-aminobutyric acid type A receptor (GABAAR) subtypes are differentially expressed and mediate distinct functions at neuronal level. In this study we have investigated GABAAR-mediated modulation of the spontaneous activity patterns of primary neuronal networks from murine frontal cortex by characterizing the effects induced by a wide selection of pharmacological tools at a plethora of activity parameters in microelectrode array (MEA) recordings. The basic characteristics of the primary cortical neurons used in the recordings were studied in some detail, and the expression levels of various GABAAR subunits were investigated by western blotting and RT-qPCR. In the MEA recordings, the pan-GABAAR agonist muscimol and the GABABR agonist baclofen were observed to mediate phenotypically distinct changes in cortical network activity. Selective augmentation of αβγ GABAAR signaling by diazepam and of δ-containing GABAAR (δ-GABAAR) signaling by DS1 produced pronounced changes in the majority of the activity parameters, both drugs mediating similar patterns of activity changes as muscimol. The apparent importance of δ-GABAAR signaling for network activity was largely corroborated by the effects induced by the functionally selective δ-GABAAR agonists THIP and Thio-THIP, whereas the δ-GABAAR selective potentiator DS2 only mediated modest effects on network activity, even when co-applied with low THIP concentrations. Interestingly, diazepam exhibited dramatically right-shifted concentration-response relationships at many of the activity parameters when co-applied with a trace concentration of DS1 compared to when applied alone. In contrast, the potencies and efficacies displayed by DS1 at the networks were not substantially altered by the concomitant presence of diazepam. In conclusion, the holistic nature of the information extractable from the MEA recordings offers interesting insights into the contributions of various GABAAR subtypes/subgroups to cortical network activity and the putative functional interplay between these receptors in these neurons

Human β-Defensin 2 Mutations Are Associated With Asthma and Atopy in Children and Its Application Prevents Atopic Asthma in a Mouse Model

Asthma and allergies are complex, chronic inflammatory diseases in which genetic and environmental factors are crucial. Protection against asthma and allergy development in the context of farming environment is established by early animal contact, unpasteurized milk consumption and gut microbiota maturation. The human β-defensin 2 (hBD-2) is a host defense peptide present almost exclusively in epithelial tissues, with pronounced immunomodulatory properties, which has recently been shown to ameliorate asthma and IBD in animal models. We hypothesized that adequate hBD-2 secretion plays a role in the protection against asthma and allergy development and that genetic variations in the complex gene locus coding for hBD-2 may be a risk factor for developing these diseases, if as a consequence, hBD-2 is insufficiently produced. We used MALDI-TOF MS genotyping, sequencing and a RFLP assay to study the genetic variation including mutations, polymorphisms and copy number variations in the locus harboring both genes coding for hBD-2 (DEFB4A and DEFB4B). We administered hBD-2 orally in a mouse model of house dust mite (HDM)-asthma before allergy challenge to explore its prophylactic potential, thereby mimicking a protective farm effect. Despite the high complexity of the region harboring DEFB4A and DEFB4B we identified numerous genetic variants to be associated with asthma and allergy in the GABRIELA Ulm population of 1,238 children living in rural areas, including rare mutations, polymorphisms and a lack of the DEFB4A. Furthermore, we found that prophylactic oral administration of hBD-2 significantly curbed lung resistance and pulmonary inflammation in our HDM mouse model. These data indicate that inadequate genetic capacity for hBD-2 is associated with increased asthma and allergy risk while adequate and early hBD-2 administration (in a mouse model) prevents atopic asthma. This suggests that hBD-2 could be involved in the protective farm effect and may be an excellent candidate to confer protection against asthma development

Simulating open quantum systems: from many-body interactions to stabilizer pumping

In a recent experiment, Barreiro et al. demonstrated the fundamental building blocks of an open-system quantum simulator with trapped ions [Nature 470, 486 (2011)]. Using up to five ions, single- and multi-qubit entangling gate operations were combined with optical pumping in stroboscopic sequences. This enabled the implementation of both coherent many-body dynamics as well as dissipative processes by controlling the coupling of the system to an artificial, suitably tailored environment. This engineering was illustrated by the dissipative preparation of entangled two- and four-qubit states, the simulation of coherent four-body spin interactions and the quantum non-demolition measurement of a multi-qubit stabilizer operator. In the present paper, we present the theoretical framework of this gate-based ("digital") simulation approach for open-system dynamics with trapped ions. In addition, we discuss how within this simulation approach minimal instances of spin models of interest in the context of topological quantum computing and condensed matter physics can be realized in state-of-the-art linear ion-trap quantum computing architectures. We outline concrete simulation schemes for Kitaev's toric code Hamiltonian and a recently suggested color code model. The presented simulation protocols can be adapted to scalable and two-dimensional ion-trap architectures, which are currently under development.Comment: 27 pages, 9 figures, submitted to NJP Focus on Topological Quantum Computatio

KELT-1b: A Strongly Irradiated, Highly Inflated, Short Period, 27 Jupiter-mass Companion Transiting a mid-F Star

We present the discovery of KELT-1b, the first transiting low-mass companion from the wide-field Kilodegree Extremely Little Telescope-North (KELT-North) survey. The V=10.7 primary is a mildly evolved, solar-metallicity, mid-F star. The companion is a low-mass brown dwarf or super-massive planet with mass of 27.23+/-0.50 MJ and radius of 1.110+0.037-0.024 RJ, on a very short period (P=1.21750007) circular orbit. KELT-1b receives a large amount of stellar insolation, with an equilibrium temperature assuming zero albedo and perfect redistribution of 2422 K. Upper limits on the secondary eclipse depth indicate that either the companion must have a non-zero albedo, or it must experience some energy redistribution. Comparison with standard evolutionary models for brown dwarfs suggests that the radius of KELT-1b is significantly inflated. Adaptive optics imaging reveals a candidate stellar companion to KELT-1, which is consistent with an M dwarf if bound. The projected spin-orbit alignment angle is consistent with zero stellar obliquity, and the vsini of the primary is consistent with tidal synchronization. Given the extreme parameters of the KELT-1 system, we expect it to provide an important testbed for theories of the emplacement and evolution of short-period companions, and theories of tidal dissipation and irradiated brown dwarf atmospheres.Comment: 30 pages, 19 figures. Submitted to Ap

Transformation of spin information into large electrical signals via carbon nanotubes

Spin electronics (spintronics) exploits the magnetic nature of the electron, and is commercially exploited in the spin valves of disc-drive read heads. There is currently widespread interest in using industrially relevant semiconductors in new types of spintronic devices based on the manipulation of spins injected into a semiconducting channel between a spin-polarized source and drain. However, the transformation of spin information into large electrical signals is limited by spin relaxation such that the magnetoresistive signals are below 1%. We overcome this long standing problem in spintronics by demonstrating large magnetoresistance effects of 61% at 5 K in devices where the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 micron gap between epitaxial electrodes of the highly spin polarized manganite La0.7Sr0.3MnO3. This improvement arises because the spin lifetime in nanotubes is long due the small spin-orbit coupling of carbon, because the high nanotube Fermi velocity permits the carrier dwell time to not significantly exceed this spin lifetime, because the manganite remains highly spin polarized up to the manganite-nanotube interface, and because the interfacial barrier is of an appropriate height. We support these latter statements regarding the interface using density functional theory calculations. The success of our experiments with such chemically and geometrically different materials should inspire adventure in materials selection for some future spintronicsComment: Content highly modified. New title, text, conclusions, figures and references. New author include

KELT-2Ab: A Hot Jupiter Transiting the Bright (V=8.77) Primary Star of a Binary System

We report the discovery of KELT-2Ab, a hot Jupiter transiting the bright (V=8.77) primary star of the HD 42176 binary system. The host is a slightly evolved late F-star likely in the very short-lived "blue-hook" stage of evolution, with \teff=6148\pm48{\rm K}, $\log{g}=4.030_{-0.026}^{+0.015}$ and \feh=0.034\pm0.78. The inferred stellar mass is $M_*=1.314_{-0.060}^{+0.063}$\msun\ and the star has a relatively large radius of $R_*=1.836_{-0.046}^{+0.066}$\rsun. The planet is a typical hot Jupiter with period $4.11379\pm0.00001$ days and a mass of $M_P=1.524\pm0.088$\mj\ and radius of $R_P=1.290_{-0.050}^{+0.064}$\rj. This is mildly inflated as compared to models of irradiated giant planets at the $\sim$4 Gyr age of the system. KELT-2A is the third brightest star with a transiting planet identified by ground-based transit surveys, and the ninth brightest star overall with a transiting planet. KELT-2Ab's mass and radius are unique among the subset of planets with $V<9$ host stars, and therefore increases the diversity of bright benchmark systems. We also measure the relative motion of KELT-2A and -2B over a baseline of 38 years, robustly demonstrating for the first time that the stars are bound. This allows us to infer that KELT-2B is an early K-dwarf. We hypothesize that through the eccentric Kozai mechanism KELT-2B may have emplaced KELT-2Ab in its current orbit. This scenario is potentially testable with Rossiter-McLaughlin measurements, which should have an amplitude of $\sim$44 m s$^{-1}$.Comment: 9 pages, 2 tables, 4 figures. A short video describing this paper is available at http://www.youtube.com/watch?v=wVS8lnkXXlE. Revised to reflect the ApJL version. Note that figure 4 is not in the ApJL versio

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Applications of Field-Theoretic Renormalization Group Methods to Reaction-Diffusion Problems

We review the application of field-theoretic renormalization group (RG) methods to the study of fluctuations in reaction-diffusion problems. We first investigate the physical origin of universality in these systems, before comparing RG methods to other available analytic techniques, including exact solutions and Smoluchowski-type approximations. Starting from the microscopic reaction-diffusion master equation, we then pedagogically detail the mapping to a field theory for the single-species reaction k A -> l A (l < k). We employ this particularly simple but non-trivial system to introduce the field-theoretic RG tools, including the diagrammatic perturbation expansion, renormalization, and Callan-Symanzik RG flow equation. We demonstrate how these techniques permit the calculation of universal quantities such as density decay exponents and amplitudes via perturbative eps = d_c - d expansions with respect to the upper critical dimension d_c. With these basics established, we then provide an overview of more sophisticated applications to multiple species reactions, disorder effects, L'evy flights, persistence problems, and the influence of spatial boundaries. We also analyze field-theoretic approaches to nonequilibrium phase transitions separating active from absorbing states. We focus particularly on the generic directed percolation universality class, as well as on the most prominent exception to this class: even-offspring branching and annihilating random walks. Finally, we summarize the state of the field and present our perspective on outstanding problems for the future.Comment: 10 figures include