Gallium oxide and gadolinium gallium oxide insulators on Si δ-doped GaAs/AlGaAs heterostructures

Test devices have been fabricated on two specially grown GaAs/AlGaAs wafers with 10 nm thick gate dielectrics composed of either Ga<sub>2</sub>O<sub>3</sub> or a stack of Ga<sub>2</sub>O<sub>3</sub> and Gd<sub>0.25</sub>Ga<sub>0.15</sub>O<sub>0.6</sub>. The wafers have two GaAs transport channels either side of an AlGaAs barrier containing a Si delta-doping layer. Temperature dependent capacitance-voltage (C-V) and current-voltage (I-V) studies have been performed at temperatures between 10 and 300 K. Bias cooling experiments reveal the presence of DX centers in both wafers. Both wafers show a forward bias gate leakage that is by a single activated channel at higher temperatures and by tunneling at lower temperatures. When Gd<sub>0.25</sub>Ga<sub>0.15</sub>O<sub>0.6</sub> is included in a stack with 1 nm of Ga<sub>2</sub>O<sub>3</sub> at the interface, the gate leakage is greatly reduced due to the larger band gap of the Gd<sub>0.25</sub>Ga<sub>0.15</sub>O<sub>0.6</sub> layer. The different band gaps of the two oxides result in a difference in the gate voltage at the onset of leakage of ~3 V. However, the inclusion of Gd<sub>0.25</sub>Ga<sub>0.15</sub>O<sub>0.6</sub> in the gate insulator introduces many oxide states (≤4.70Ã�Â�10<sup>12</sup> cm<sup>âÂ�Â�2</sup>). Transmission electron microscope images of the interface region show that the growth of a Gd<sub>0.25</sub>Ga<sub>0.15</sub>O<sub>0.6</sub> layer on Ga<sub>2</sub>O<sub>3</sub> disturbs the well ordered Ga<sub>2</sub>O<sub>3</sub>/GaAs interface. We therefore conclude that while including Gd<sub>0.25</sub>Ga<sub>0.15</sub>O<sub>0.6</sub> in a dielectric stack with Ga<sub>2</sub>O<sub>3</sub> is necessary for use in device applications, the inclusion of Gd decreases the quality of the Ga<sub>2</sub>O<sub>3</sub>/GaAs interface and near interface region by introducing roughness and a large number of defect states

Hyperpolarisation-activated ion channels as a target for nitric oxide-cGMP signalling in the rat brain.

Most of the known physiological effects of nitric oxide (NO) in the brain are mediated by activation of specialised guanylyl cyclase-coupled receptors, leading to a rise in intracellular cGMP. Apart from protein kinase activation little is known about subsequent cGMP signal transduction. In optic nerve axons, hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels, which bind cGMP (and cAMP) directly, appear to be a target. The objective was to test this possibility directly using electrophysiological methods. Studies were initially carried out by recording extracellularly from Schaffer collateral/commissural axons in hippocampal slices, where the NO-cGMP pathway contributes to synaptic plasticity. Pharmacological manipulation of the NO-cGMP pathway failed to affect significantly axonal conduction at 0.2 - 5 Hz, a frequency range in which HCN channels were found to influence conduction reliability. Raising cAMP levels were similarly ineffective suggesting that, unlike in optic nerve, the subunit composition is likely to render the HCN channels relatively cyclic nucleotide-insensitive. Next, I investigated two neuronal types known to express the cyclic nucleotide-sensitive HCN channel subunits (HCN2 and/or HCN4), namely the principal cells of the medial nucleus of the trapezoid body and of the deep cerebellar nuclei. Using whole-cell voltage clamp, I found no reproducible evidence of regulation of HCN channel function by NO, even though exogenous cGMP was effective routinely and the neurones expressed NO-activated guanylyl cyclase, as shown by immunohistochemistry. I then carried out a series of non-invasive sharp electrode current-clamp recordings in deep cerebellar nuclear neurones. Using the characteristic voltage sag as an index of HCN channel operation, exogenous NO was found to modulate the channels reproducibly. Attempts to refine the original whole-cell recording solution to optimise preservation of the NO-cGMP pathway failed to restore NO-sensitivity. Minimising cell dialysis by using the perforated-patch variant of the whole-cell method, however, was successful. The results provide direct evidence that HCN channels are potential downstream mediators of NO-cGMP signaling in the deep cerebellar nuclei and suggest that the importance of this transduction pathway may have been previously overlooked because of unsuitable recording methods. 3

An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles.

The tumor necrosis factor (TNF) alpha gene lies within the class III region of the major histocompatibility complex (MHC), telomeric to the class II and centromeric to the class I region. We have recently described the first polymorphism within the human TNF-alpha locus. This is biallelic and lies within the promoter region. Frequency analysis of the TNF-alpha polymorphism, using the polymerase chain reaction and single-stranded conformational polymorphism, in HLA-typed individuals, reveals a very strong association between the uncommon TNF allele and HLA A1, B8, and DR3 alleles. This is the first association between TNF-alpha and other MHC alleles and raises the possibility that the uncommon TNF-alpha allele may contribute to the many autoimmune associations of the A1,B8,DR3 haplotype

Multidimensional analysis of human intestinal fluid composition

The oral administration of solid dosage forms is the commonest method to achieve systemic therapy and relies on the drug’s solubility in human intestinal fluid (HIF), a key factor that influences bioavailability and biopharmaceutical classification. However, HIF is difficult to obtain and is known to be variable, which has led to the development of a range of simulated intestinal fluid (SIF) systems to determine drug solubility in vitro. In this study we have applied a novel multidimensional approach to analyse and characterise HIF composition using a published data set in both fasted and fed states with a view to refining the existing SIF approaches. The data set provided 152 and 172 measurements of five variables (total bile salt, phospholipid, total free fatty acid, cholesterol and pH) in time-dependent HIF samples from 20 volunteers in the fasted and fed state, respectively. The variable data sets for both fasted state and fed state are complex, do not follow normal distributions but the amphiphilic variable concentrations are correlated. When plotted 2-dimensionally a generally ellipsoid shaped data cloud with a positive slope is revealed with boundaries that enclose published fasted or fed HIF compositions. The data cloud also encloses the majority of fasted state and fed state SIF recipes and illustrates that the structured nature of design of experiment (DoE) approaches does not optimally cover the variable space and may examine media compositions that are not biorelevant. A principal component analysis in either fasted or fed state in combination with fitting an ellipsoid shape to enclose the data results in 8 points that capture over 95% of the compositional variability of HIF. The variable’s average rate of concentration change in both fasted state and fed state over a short time scale (10 min) is zero and a Euclidean analysis highlights differences between the fasted and fed states and among individual volunteers. The results indicate that a 9-point DoE (8 + 1 central point) could be applied to investigate drug solubility in vitro and provide statistical solubility limits. In addition, a single point could provide a worst-case solubility measurement to define the lowest biopharmaceutical classification boundary or for use during drug development. This study has provided a novel description of HIF composition. The approach could be expanded in multiple ways by incorporation of further data sets to improve the statistical coverage or to cover specific patient groups (e.g., paediatric). Further development might also be possible to analyse information on the time dependent behaviour of HIF and to guide HIF sampling and analysis protocols

The Effect of Large Amplitude Fluctuations in the Ginzburg-Landau Phase Transition

The lattice Ginzburg-Landau model in d=3 and d=2 is simulated, for different values of the coherence length $\xi$ in units of the lattice spacing $a$, using a Monte Carlo method. The energy, specific heat, vortex density $v$, helicity modulus $\Gamma_\mu$ and mean square amplitude are measured to map the phase diagram on the plane $T-\xi$. When amplitude fluctuations, controlled by the parameter $\xi$, become large ($\xi \sim 1$) a proliferation of vortex excitations occurs changing the phase transition from continuous to first order.Comment: 4 pages, 5 postscript (eps) figure

A note on the appearance of self-dual Yang-Mills fields in integrable hierarchies

A family of mappings from the solution spaces of certain generalized Drinfeld-Sokolov hierarchies to the self-dual Yang-Mills system on R^{2,2} is described. This provides an extension of the well-known relationship between self-dual connections and integrable hierarchies of AKNS and Drinfeld-Sokolov type

Toda Soliton Mass Corrections and the Particle--Soliton Duality Conjecture

We compute quantum corrections to soliton masses in affine Toda theories with imaginary exponentials based on the nonsimply-laced Lie algebras $c_n^{(1)}$. We find that the soliton mass ratios renormalize nontrivially, in the same manner as those of the fundamental particles of the theories with real exponentials based on the nonsimply-laced algebras $b_n^{(1)}$. This gives evidence that the conjectured relation between solitons in one Toda theory and fundamental particles in a dual Toda theory holds also at the quantum level. This duality can be seen as a toy model for S-duality.Comment: LATEX, 17 pages, no figures Note added at end of discussio

Generalized Drinfeld-Sokolov Hierarchies II: The Hamiltonian Structures

In this paper we examine the bi-Hamiltonian structure of the generalized KdV-hierarchies. We verify that both Hamiltonian structures take the form of Kirillov brackets on the Kac-Moody algebra, and that they define a coordinated system. Classical extended conformal algebras are obtained from the second Poisson bracket. In particular, we construct the $W_n^l$ algebras, first discussed for the case $n=3$ and $l=2$ by A. Polyakov and M. Bershadsky.Comment: 41 page

Preceding rule induction with instance reduction methods

A new prepruning technique for rule induction is presented which applies instance reduction before rule induction. An empirical evaluation records the predictive accuracy and size of rule-sets generated from 24 datasets from the UCI Machine Learning Repository. Three instance reduction algorithms (Edited Nearest Neighbour, AllKnn and DROP5) are compared. Each one is used to reduce the size of the training set, prior to inducing a set of rules using Clark and Boswell's modification of CN2. A hybrid instance reduction algorithm (comprised of AllKnn and DROP5) is also tested. For most of the datasets, pruning the training set using ENN, AllKnn or the hybrid significantly reduces the number of rules generated by CN2, without adversely affecting the predictive performance. The hybrid achieves the highest average predictive accuracy

Solitons and Vertex Operators in Twisted Affine Toda Field Theories

Affine Toda field theories in two dimensions constitute families of integrable, relativistically invariant field theories in correspondence with the affine Kac-Moody algebras. The particles which are the quantum excitations of the fields display interesting patterns in their masses and coupling and which have recently been shown to extend to the classical soliton solutions arising when the couplings are imaginary. Here these results are extended from the untwisted to the twisted algebras. The new soliton solutions and their masses are found by a folding procedure which can be applied to the affine Kac-Moody algebras themselves to provide new insights into their structures. The relevant foldings are related to inner automorphisms of the associated finite dimensional Lie group which are calculated explicitly and related to what is known as the twisted Coxeter element. The fact that the twisted affine Kac-Moody algebras possess vertex operator constructions emerges naturally and is relevant to the soliton solutions.Comment: 27 pages (harvmac) + 3 figures (LaTex) at the end of the file, Swansea SWAT/93-94/1