Pharmacological differences of GABAergic compounds: a pharmacodynamic characterization

This thesis describes different ways of exploring the pharmacological and therapeutic effects of novel GABA-ergic and GABA-like agents in humans. Systematic pharmacodynamic evaluations, using well-characterised positive controls, can confirm or refute the unique pharmacological properties of GABAA-subtype selective drugs in healthy volunteers. Such studies can help to predict dosing regimens and therapeutic advantages of these drugs. The distribution of different GABAA-receptor subtypes provides clues for their functional relevance. This knowledge can be used to optimise the desirable and undesirable effect profiles of selective GABA-ergic drugs. Very little is still known about the pathophysiological relevance of GABA-systems in CNS-disorders, although GABA-ergic treatments are in use for a wide range of clinical conditions. The availability of novel compounds with well defined pharmacological characteristics can clarify the involvement of these mechanisms in normal or abnormal physiology. This thesis hopes to show that carefully designed studies, using a range of CNS-measurement that reflect different GABAergic systems, can aid in the development of new GABA-ergic drugs, and help to unravel the role of the different GABA-ergic systems in health and disease.UBL - phd migration 201

Adaptive Mesh Refinement for Characteristic Grids

I consider techniques for Berger-Oliger adaptive mesh refinement (AMR) when numerically solving partial differential equations with wave-like solutions, using characteristic (double-null) grids. Such AMR algorithms are naturally recursive, and the best-known past Berger-Oliger characteristic AMR algorithm, that of Pretorius & Lehner (J. Comp. Phys. 198 (2004), 10), recurses on individual "diamond" characteristic grid cells. This leads to the use of fine-grained memory management, with individual grid cells kept in 2-dimensional linked lists at each refinement level. This complicates the implementation and adds overhead in both space and time. Here I describe a Berger-Oliger characteristic AMR algorithm which instead recurses on null \emph{slices}. This algorithm is very similar to the usual Cauchy Berger-Oliger algorithm, and uses relatively coarse-grained memory management, allowing entire null slices to be stored in contiguous arrays in memory. The algorithm is very efficient in both space and time. I describe discretizations yielding both 2nd and 4th order global accuracy. My code implementing the algorithm described here is included in the electronic supplementary materials accompanying this paper, and is freely available to other researchers under the terms of the GNU general public license.Comment: 37 pages, 15 figures (40 eps figure files, 8 of them color; all are viewable ok in black-and-white), 1 mpeg movie, uses Springer-Verlag svjour3 document class, includes C++ source code. Changes from v1: revised in response to referee comments: many references added, new figure added to better explain the algorithm, other small changes, C++ code updated to latest versio

Quantized Skyrmion Fields in 2+1 Dimensions

A fully quantized field theory is developped for the skyrmion topological excitations of the O(3) symmetric CP$^1$-Nonlinear Sigma Model in 2+1D. The method allows for the obtainment of arbitrary correlation functions of quantum skyrmion fields. The two-point function is evaluated in three different situations: a) the pure theory; b) the case when it is coupled to fermions which are otherwise non-interacting and c) the case when an electromagnetic interaction among the fermions is introduced. The quantum skyrmion mass is explicitly obtained in each case from the large distance behavior of the two-point function and the skyrmion statistics is inferred from an analysis of the phase of this function. The ratio between the quantum and classical skyrmion masses is obtained, confirming the tendency, observed in semiclassical calculations, that quantum effects will decrease the skyrmion mass. A brief discussion of asymptotic skyrmion states, based on the short distance behavior of the two-point function, is also presented.Comment: Accepted for Physical Review

Muon-spin-relaxation study of the magnetic penetration depth in MgB2

The magnetic vortex lattice (VL) of polycrystalline MgB2 has been investigated by transverse-field muon-spin-relaxation (TF-MuSR). The evolution of TF-MuSR depolarization rate, sigma, that is proportional to the second moment of the field distribution of the VL has been studied as a function of temperature and applied magnetic field. The low temperature value s exhibits a pronounced peak near Hext = 75 mT. This behavior is characteristic of strong pinning induced distortions of the VL which put into question the interpretation of the low-field TF-MuSR data in terms of the magnetic penetration depth lambda(T). An approximately constant value of sigma, such as expected for an ideal VL in the London-limit, is observed at higher fields of Hext > 0.4 T. The TF-MuSR data at Hext = 0.6 T are analyzed in terms of a two-gap model. We obtain values for the gap size of D1 = 6.0 meV (2D1/kBTc = 3.6), D2 = 2.6 meV (2D2/kBTc = 1.6), a comparable spectral weight of the two bands and a zero temperature value for the magnetic penetration depth of lambda = 100 nm. In addition, we performed MuSR-measurements in zero external field (ZF-MuSR). We obtain evidence that the muon site (at low temperature) is located on a ring surrounding the center of the boron hexagon. Muon diffusion sets in already at rather low temperature of T > 10 K. The nuclear magnetic moments can account for the observed relaxation rate and no evidence for electronic magnetic moments has been obtained.Comment: 15 pages, 4 figure

Mixed state properties of superconducting MgB2 single crystals

We report on measurements of the magnetic moment in superconducting MgB2 single crystals. We find \mu_0H_{c2}^c(0) = 3.2 T, \mu_0H_{c2}^{ab}(0) = 14.5 T, \gamma = 4.6, \mu_0H_c(0) = 0.28 T, and \kappa(T_c) = 4.7. The standard Ginzburg-Landau and London model relations lead to a consistent data set and indicate that MgB2 is a clean limit superconductor of intermediate coupling strength with very pronounced anisotropy effects

Far-infrared transmission studies of c-axis oriented superconducting MgB2 thin film

We reported far-infrared transmission measurements on a c-axis oriented superconducting MgB$_{2}$ thin film in the frequency range of 30 $\sim$ 250 cm$^{-1}$. We found that these measurements were sensitive to values of scattering rate $1/\tau$ and superconducting gap $2\Delta$. By fitting the experimental transmission spectra at 40 K and below, we obtained $1/\tau =$ (700 $\sim$ 1000) cm$^{-1}$ and $2\Delta (0)\cong$ 42 cm$^{-1}$. These two quantities suggested that MgB$_{2}$ belong to the dirty limit.Comment: submitted at May

Quantum Vacuum Experiments Using High Intensity Lasers

The quantum vacuum constitutes a fascinating medium of study, in particular since near-future laser facilities will be able to probe the nonlinear nature of this vacuum. There has been a large number of proposed tests of the low-energy, high intensity regime of quantum electrodynamics (QED) where the nonlinear aspects of the electromagnetic vacuum comes into play, and we will here give a short description of some of these. Such studies can shed light, not only on the validity of QED, but also on certain aspects of nonperturbative effects, and thus also give insights for quantum field theories in general.Comment: 9 pages, 8 figur

Variation in enteric methane emissions among cows on commercial dairy farms

Methane (CH4) emissions by dairy cows vary with feed intake and diet composition. Even when fed on the same diet at the same intake, however, variation between cows in CH4 emissions can be substantial. The extent of variation in CH4 emissions among dairy cows on commercial farms is unknown, but developments in methodology now permit quantification of CH4 emissions by individual cows under commercial conditions. The aim of this research was to assess variation among cows in emissions of eructed CH4 during milking on commercial dairy farms. Enteric CH4 emissions from 1,964 individual cows across 21 farms were measured for at least 7 days per cow using CH4 analysers at robotic milking stations. Cows were predominantly of Holstein Friesian breed and remained on the same feeding systems during sampling. Effects of explanatory variables on average CH4 emissions per individual cow were assessed by fitting a linear mixed model. Significant effects were found for week of lactation, daily milk yield and farm. The effect of milk yield on CH4 emissions varied among farms. Considerable variation in CH4 emissions was observed among cows after adjusting for fixed and random effects, with the coefficient of variation ranging from 22 to 67% within farms. This study confirms that enteric CH4 emissions vary among cows on commercial farms, suggesting that there is considerable scope for selecting individual cows and management systems with reduced emissions

A survey on probabilistic broadcast schemes for wireless ad hoc networks

Broadcast or flooding is a dissemination technique of paramount importance in wireless ad hoc networks. The broadcast scheme is widely used within routing protocols by a wide range of wireless ad hoc networks such as mobile ad hoc networks, vehicular ad hoc networks, and wireless sensor networks, and used to spread emergency messages in critical scenarios after a disaster scenario and/or an accidents. As the type broadcast scheme used plays an important role in the performance of the network, it has to be selected carefully. Though several types of broadcast schemes have been proposed, probabilistic broadcast schemes have been demonstrated to be suitable schemes for wireless ad hoc networks due to a range of benefits offered by them such as low overhead, balanced energy consumption, and robustness against failures and mobility of nodes. In the last decade, many probabilistic broadcast schemes have been proposed by researchers. In addition to reviewing the main features of the probabilistic schemes found in the literature, we also present a classification of the probabilistic schemes, an exhaustive review of the evaluation methodology including their performance metrics, types of network simulators, their comparisons, and present some examples of real implementations, in this paper

Menus for Feeding Black Holes

Black holes are the ultimate prisons of the Universe, regions of spacetime where the enormous gravity prohibits matter or even light to escape to infinity. Yet, matter falling toward the black holes may shine spectacularly, generating the strongest source of radiation. These sources provide us with astrophysical laboratories of extreme physical conditions that cannot be realized on Earth. This chapter offers a review of the basic menus for feeding matter onto black holes and discusses their observational implications.Comment: 27 pages. Accepted for publication in Space Science Reviews. Also to appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher