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Brian Robertson

Publications and source records attributed to Brian Robertson.

15 recordsLinked to original sources
PubMed2006

Aberration correction in an adaptive free-space optical interconnect with an error diffusion algorithm.

Aberration correction within a free-space optical interconnect based on a spatial light modulator for beam steering and holographic wavefront correction is presented. The wavefront sensing technique is based on an extension of a modal wavefront sensor described by Neil et al. [J. Opt. Soc. Am. A 17, 1098 (2000)], which uses a diffractive element. In this analysis such a wavefront sensor is adapted with an error diffusion algorithm that yields a low reconstruction error and fast reconfigurability. Improvement of the beam propagation quality (Strehl ratio) for different channels across the input plane is achieved. However, due to the space invariancy of the system, a trade-off among the beam propagation quality for channels is obtained. Experimental results are presented and discussed.

Journal Article↗
PubMed2006

Cross-talk analysis in a telecentric adaptive free-space optical relay based on a spatial light modulator.

We present an analysis of the performance limit of an adaptive multichannel free-space optical interconnect based on a spatial light modulator (SLM). The SLM function is to provide an active alignment of the signal beam in the detector plane. A thorough cross-talk analysis based on the diffractive properties of an ideal SLM in an isoplanatic optical system is shown. We analyze the performance in terms of the bit-error rate (BER) due to cross talk between different channels in the optical interconnect for different alignment states and for different phase-modulation schemes.

Journal Article↗
PubMed2006

Modelling infectious disease - time to think outside the box?

Models occupy an essential position in the study of infectious disease as a result of the ethical problems of exposing humans to potentially lethal agents. Deliberately induced infections in well-defined animal models provide much useful information about disease processes in an approximation of their natural context. Despite this, animal models are not the natural disease process, and recent experimental advances show, perhaps not unsurprisingly, that there are large differences between natural infections and animal models. Focusing on mouse models of bacterial pathogens, we discuss some of these discrepancies and suggest ways of improving model systems in the future.

Animals↗
PubMed2005

Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies.

Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson's and Alzheimer's diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility. Previous work suggested that BDS toxins ("blood depressing substance," from the sea anemone Anemonia sulcata) were specific blockers for rapidly inactivating Kv3.4 channels, and consequently these toxins are increasingly used as diagnostic agents for Kv3.4 subunits in central neurons. However, precisely how selective are these toxins for this important CNS protein? We show that BDS is not selective for Kv3.4 but markedly inhibits current through Kv3.1 and Kv3.2 channels. Inhibition comes about not by "pore block" but by striking modification of Kv3 gating kinetics and voltage dependence. Activation and inactivation kinetics are slowed by BDS-I and BDS-II, and V(1/2) for activation is shifted to more positive voltages. Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 reveals that BDS acts via voltage-sensing domains, and, consistent with this, ON gating currents from nonconducting Kv3.2 are markedly inhibited. The altered kinetics and gating properties, combined with lack of subunit selectivity with Kv3 subunits, seriously affects the usefulness of BDS toxins in CNS studies. Furthermore, our results do not easily fit with the voltage sensor "paddle" structure proposed recently for Kv channels. Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction.

Animals↗
PubMed2005

Taking a new look at the hosted applications model.

Deciding whether to adopt a hosted applications model for your organization? Advantages--rapid time to value, no hardware and software maintenance responsibilities, reduced IT staff support burden. Disadvantages--reliance on the Internet to deliver applications, concerns about security, and limited customization options with some vendors.

Information Systems↗
PubMed2005

Six steps to an effective denials management program.

The following six steps can help you manage denials management issues in your organization: Create standard definitions of denial types. Establish a denial hierarchy. Establish a centralized denial database. Develop key performance indicators. Build responsibility matrices. Measure, monitor, and take action.

Accounts Payable and Receivable↗
PubMed2004

Design and analysis of an adaptive board-to-board dynamic holographic interconnect.

We describe the design and analysis of an adaptive free-space optical interconnect between two circuit boards in a standard electronic backplane. An array of vertical-cavity surface-emitting lasers is used as the transmitter, and this communicates with a detector array on the receiver circuit board. Routing is achieved with a holographic crossbar that has a ferroelectric liquid-crystal spatial light modulator to display binary phase computer-generated holograms. A detailed analysis of a 48-channel interconnect designed to operate at 1 (Gbytes/s)/channel indicates that such a switch will operate successfully given typical components and card misalignments.

Journal Article↗
PubMed2004

Characterisation of hyperpolarization-activated currents (I(h)) in the medial septum/diagonal band complex in the mouse.

Hyperpolarization-activated cyclic nucleotide gated (HCN) channel subunits are distributed widely, but selectively, in the central nervous system, and underlie hyperpolarization-activated currents (I(h)) that contribute to rhythmicity in a variety of neurons. This study investigates, using current and voltage-clamp techniques in brain slices from young mice, the properties of I(h) currents in medial septum/diagonal band (MS/DB) neurons. Subsets of neurons in this complex, including GABAergic and cholinergic neurons, innervate the hippocampal formation, and play a role in modulating hippocampal theta rhythm. In support of a potential role for I(h) in regulating MS/DB firing properties and consequently hippocampal neuron rhythmicity, I(h) currents were present in around 60% of midline MS/DB complex neurons. The I(h) currents were sensitive to the selective blocker ZD7288 (10 microM). The I(h) current had a time constant of activation of around 220 ms (at -130 mV), and tail current analysis revealed a half-activation voltage of -98 mV. Notably, the amplitude and kinetics of I(h) currents in MS/DB neurons were insensitive to the cAMP membrane permeable analogue 8-bromo-cAMP (1 mM), and application of muscarine (100 microM). Immunofluoresence using antibodies against HCN1, 2 and 4 channel subunits revealed that all three HCN subunits are expressed in neurons in the MS/DB, including neurons that express the calcium binding protein parvalbumin (marker of fast spiking GABAergic septo-hippocampal projection neurons). The results demonstrate, for the first time, that specific HCN channel subunits are likely to be coexpressed in subsets of MS/DB neurons, and that the resultant I(h) currents show both similarities, and differences, to previously described I(h) currents in other CNS neurons.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2004

Phenotypic characterization and genealogical tracing in an Afrikaner schizophrenia database.

Founder populations hold tremendous promise for mapping genes for complex traits, as they offer less genetic and environmental heterogeneity and greater potential for genealogical research. Not all founder populations are equally valuable, however. The Afrikaner population meets several criteria that make it an ideal population for mapping complex traits, including founding by a small number of initial founders that likely allowed for a relatively restricted set of mutations and a large current population size that allows identification of a sufficient number of cases. Here, we examine the potential to conduct genealogical research in this population and present initial results indicating that accurate genealogical tracing for up to 17 generations is feasible. We also examine the clinical similarities of schizophrenia cases diagnosed in South Africa and those diagnosed in other, heterogeneous populations, specifically the US. We find that, with regard to basic sample descriptors and cardinal symptoms of disease, the two populations are equivalent. It is, therefore, likely that results from our genetic study of schizophrenia will be applicable to other populations. Based on the results presented here, the history and current size of the population, as well as our previous analysis addressing the extent of background linkage disequilibrium (LD) in the Afrikaners, we conclude that the Afrikaner population is likely an appropriate founder population to map genes for schizophrenia using both linkage and LD approaches.

Adult↗
PubMed2003

Design and implementation of a modulator-based free-space optical backplane for multiprocessor applications.

Design and implementation of a free-space optical backplane for multiprocessor applications is presented. The system is designed to interconnect four multiprocessor nodes that communicate by using multiplexed 32-bit packets. Each multiprocessor node is electrically connected to an optoelectronic VLSI chip which implements the hyperplane interconnection architecture. The chips each contain 256 optical transmitters (implemented as dual-rail multiple quantum-well modulators) and 256 optical receivers. A rigid free-space microoptical interconnection system that interconnects the transceiver chips in a 512-channel unidirectional ring is implemented. Full design, implementation, and operational details are provided.

Journal Article↗
PubMed2002

Adaptive beam steering implemented in a ferroelectric liquid-crystal spatial-light-modulator free-space, fiber-optic switch.

Active alignment of a 1 x 8 free-space optical switch was studied experimentally. Optical signals, carried on single-mode fibers, were switched by a ferroelectric liquid-crystal-on-silicon spatial light modulator. Continuous measurement of the in-coupled power to the fibers provided feedback for the switch control. The switch automatically located and locked to the output fibers. An advantage with adaptive switches of a similar kind is relaxed geometrical tolerances in the switch assembly. Further, such switches can adapt to possible geometrical changes and light wavelength drift during operation.

Journal Article↗
PubMed2002

Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia.

The location of a schizophrenia susceptibility locus at chromosome 22q11 has been suggested by genome-wide linkage studies. Additional support was provided by the observation of a higher-than-expected frequency of 22q11 microdeletions in patients with schizophrenia and the demonstration that approximately 20-30% of individuals with 22q11 microdeletions develop schizophrenia or schizoaffective disorder in adolescence and adulthood. Analysis of the extent of these microdeletions by using polymorphic markers afforded further refinement of this locus to a region of approximately 1.5 Mb. Recently, a high rate of 22q11 microdeletions was also reported for a cohort of 47 patients with Childhood Onset Schizophrenia, a rare and severe form of schizophrenia with onset by age 13. It is therefore likely that this 1.5-Mb region contains one or more genes that predispose to schizophrenia. In three independent samples, we provide evidence for a contribution of the PRODH2/DGCR6 locus in 22q11-associated schizophrenia. We also uncover an unusual pattern of PRODH2 gene variation that mimics the sequence of a linked pseudogene. Several of the pseudogene-like variants we identified result in missense changes at conserved residues and may prevent synthesis of a fully functional enzyme. Our results have implications for understanding the genetic basis of the 22q11-associated psychiatric phenotypes and provide further insights into the genomic instability of this region.

Africa↗
PubMed2002

Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones.

Whole-cell patch clamp recordings were used to investigate the properties of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones at a holding potential of -20 mV. Increasing the external potassium (K(+)) concentration from 3 mM to 20 mM produced a rightward shift in the observed reversal potential of approximately 30 mV or approximately 40 mV for a K(+)-or a caesium (Cs(+))-based intracellular solution respectively, indicating the outward current was a K(+) current. The outward current was partially inhibited by the K(+) channel blocker, tetraethylammonium (TEA; IC(50)=0.15 mM). Subsequently, the background or TEA-insensitive current was measured in the presence of 1 mM TEA. The background current was reversibly inhibited by barium (Ba(2+); 300 microM, 50%) and potentiated by the application of arachidonic acid (AA; 1 mM, 62%). The volatile anaesthetic, halothane (1 mM), and the neuroprotectant, riluzole (500 microM), both reversibly inhibited the background current by 54% and 36% respectively. The background current was insensitive to changes in both intracellular and extracellular acidification. The GABA(B) and mu-opioid receptor agonists, baclofen and [D-Ala(2), N-MePhe(4)-Gly-ol(5)] enkephalin (DAMGO) both reversibly potentiated the outward current by 42% and 26% respectively. In contrast, the metabotropic glutamate receptor and acetylcholine receptor agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and muscarine both reversibly inhibited the outward current by 48% and 42% respectively. These data suggest that cerebellar Purkinje neurones possess a background current which shares several properties with recently cloned two-pore K(+) channels, particularly THIK-1.

Animals↗
PubMed2002

Presynaptic internal Ca2+ stores contribute to inhibitory neurotransmitter release onto mouse cerebellar Purkinje cells.

1. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded in mouse Purkinje cells in the presence of 1 micro M tetrodotoxin (TTX). Under these conditions, which eliminated Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs), the contribution of Ca(2+) stores to spontaneous GABA release was examined. 2. The plant alkaloid ryanodine acts as an inhibitor of endoplasmic reticulum ryanodine-sensitive Ca(2+) release channels (ryanodine receptors) at low micromolar concentrations. Ryanodine effects were confined to a subpopulation of cells tested. At 10 micro M ryanodine, 4/12 cells showed a significant increase in mean mIPSC frequency of +19.6+/-4.0% (n=4). 3. The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump inhibitor cyclopiazonic acid (CPA) produced a more robust effect. In 8/10 cells, 25 micro M CPA caused a significant increase in mean mIPSC frequency; the mean increase being +26.0+/-3.0% (n=8). Similar results were seen with thapsigargin (1-2 micro M), another SERCA pump inhibitor. 4. Ruthenium red (RuR) has been proposed to either act directly on the release machinery or block Ca(2+) pumps on internal stores. At 10 micro M RuR, all cells showed a rapid, large increase in mean mIPSC frequency of +90.4+/-16.4% (n=9). This increase was greater than that seen by agents known to modulate Ca(2+) stores and was more consistent with a direct action. At this concentration, RuR also occluded the effects of CPA. 5. For all reagents, there were no obvious effects on mean mIPSC amplitude. However, the effects on mIPSC frequency were consistent with a presynaptic action and indicate that Ca(2+) stores may contribute to spontaneous GABA release onto mouse Purkinje cells.

Animals↗