Generalization by symbolic abstraction in cascaded recurrent networks

Generalization performance in recurrent neural networks is enhanced by cascading several networks. By discretizing abstractions induced in one network, other networks can operate on a coarse symbolic level with increased performance on sparse and structural prediction tasks. The level of systematicity exhibited by the cascade of recurrent networks is assessed on the basis of three language domains. (C) 2004 Elsevier B.V. All rights reserved.

Cascaded DC-DC converter connection of photovoltaic modules

New residential scale photovoltaic (PV) arrays are commonly connected to the grid by a single dc-ac inverter connected to a series string of pv panels, or many small dc-ac inverters which connect one or two panels directly to the ac grid. This paper proposes an alternative topology of nonisolated per-panel dc-dc converters connected in series to create a high voltage string connected to a simplified dc-ac inverter. This offers the advantages of a converter-per-panel approach without the cost or efficiency penalties of individual dc-ac grid connected inverters. Buck, boost, buck-boost, and Cuk converters are considered as possible dc-dc converters that can be cascaded. Matlab simulations are used to compare the efficiency of each topology as well as evaluating the benefits of increasing cost and complexity. The buck and then boost converters are shown to be the most efficient topologies for a given cost, with the buck best suited for long strings and the boost for short strings. While flexible in voltage ranges, buck-boost, and Cuk converters are always at an efficiency or alternatively cost disadvantage.

Ciguatoxins: Cyclic polyether modulators of voltage-gated Iion channel function

Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

PhotoVoltaic DC-DC module integrated converter for novel cascaded and bypass grid connection topologies - design and optimisation

Grid connected PhotoVoltaic (PV) inverters fall into three broad categories — Central, String and Module Integrated Converers (MICs). MICs offer any avantaes in performance and flexibility, but are at a cost disadvantage. Two alternative novel approaches proposed by the author — cascaded dc-dc MICs and bypass dc-dc MICs — integrate a simple non-isolated intelligent dc-dc converter with each PV module to provide the advantages of dc-ac MICs at a lower cost. A suitable universal 150W 5A dc-dc converter design is presented based on two interleaved MOSFET half bridges. Testing shows Zero Voltage Switching (ZVS) keeps losses under 1W for bi-directional power flows up to 15W between two adjacent 12V PV modules for the bypass application, and efficiencies over 94% for most of the operational power range for the cascaded converter application. Based on the experimental results, potential optimizations to further reduce losses are discussed.

Cascaded DC-DC converter connection of photovoltaic modules

New residential scale photovoltaic (PV) arrays are commonly connected to the grid by a single DC-AC inverter connected to a series string of PV modules, or many small DC-AC inverters which connect one or two modules directly to the AC grid. This paper shows that a "converter-per-module" approach offers many advantages including individual module maximum power point tracking, which gives great flexibility in module layout, replacement, and insensitivity to shading; better protection of PV sources, and redundancy in the case of source or converter failure; easier and safer installation and maintenance; and better data gathering. Simple nonisolated per-module DC-DC converters can be series connected to create a high voltage string connected to a simplified DC-AC inverter. These advantages are available without the cost or efficiency penalties of individual DC-AC grid connected inverters. Buck, boost, buck-boost and Cuk converters are possible cascadable converters. The boost converter is best if a significant step up is required, such as with a short string of 12 PV modules. A string of buck converters requires many more modules, but can always deliver any combination of module power. The buck converter is the most efficient topology for a given cost. While flexible in voltage ranges, buck-boost and Cuk converters are always at an efficiency or alternatively cost disadvantage.

A new principle for tight junction modulation based on occludin peptides

The aim of this study was to investigate whether peptides from the extracellular loops of the tight junction protein occludin could be used as a new principle for tight junction modulation. Peptides of 4 to 47 amino acids in length and covering the two extracellular loops of the tight junction protein occludin were synthesized, and their effect on the tight junction permeability in Caco-2 cells was investigated using [C-14] mannitol as a paracellular marker. Lipopeptide derivatives of one of the active occludin peptides (OPs), synthesized by adding a lipoamino acid containing 14 carbon atoms (C-14-) to the N terminus of the peptide, were also investigated. Peptides corresponding to the N terminus of the first extracellular loop of occludin increased the permeability of the tight junctions without causing short-term toxicity. However, the peptides had an effect only when added to the basolateral side of the cells, which could be partly explained by degradation by apical peptidases and aggregate formation. By contrast, the lipopeptide C-14-OP90-103, which protects the peptide from degradation and aggregation, displayed a rapid apical effect. The L- and D-diastereomers of C-14-OP90-103 had distinctly different effects. The D-isomer, which releases intact OP90-103 from the lipoamino acid, displayed a rapid and transient increase in tight junction permeability. The L- isomer, which releases OP90-103 more rapidly, gave a more sustained increase in tight junction permeability. In conclusion, C-14-OP90-103 represents a prototype of a new class of tight junction modulators that act on the extracellular domains of tight junction proteins.

Developmental changes in expression of GABA(A) receptor-channels in rat intrinsic cardiac ganglion neurones

The effects of gamma-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at -60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABA(A) receptor agonists muscimol and taurine, and inhibited by the GABA(A) receptor antagonists, bicuculline and picrotoxin. The GABA(A0) antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABA(A) receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at -100 mV was similar to 20 times higher for intracardiac neurones obtained from neonatal rats (P2-5) compared with adult rats (P45-49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system.

Rev-erb beta regulates the expression of genes involved in lipid absorption in skeletal muscle cells - Evidence for cross-talk between orphan nuclear receptors and myokines

Rev-erbbeta is an orphan nuclear receptor that selectively blocks trans-activation mediated by the retinoic acid-related orphan receptor-alpha (RORalpha). RORalpha has been implicated in the regulation of high density lipoprotein cholesterol, lipid homeostasis, and inflammation. Rev-erbbeta and RORalpha are expressed in similar tissues, including skeletal muscle; however, the pathophysiological function of Rev-erbbeta has remained obscure. We hypothesize from the similar expression patterns, target genes, and overlapping cognate sequences of these nuclear receptors that Rev-erbbeta regulates lipid metabolism in skeletal muscle. This lean tissue accounts for > 30% of total body weight and 50% of energy expenditure. Moreover, this metabolically demanding tissue is a primary site of glucose disposal, fatty acid oxidation, and cholesterol efflux. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. We utilize ectopic expression in skeletal muscle cells to understand the regulatory role of Rev-erbbeta in this major mass peripheral tissue. Exogenous expression of a dominant negative version of mouse Rev-erbbeta decreases the expression of many genes involved in fatty acid/lipid absorption (including Cd36, and Fabp-3 and -4). Interestingly, we observed a robust induction (> 15-fold) in mRNA expression of interleukin-6, an exercise-induced myokine that regulates energy expenditure and inflammation. Furthermore, we observed the dramatic repression (> 20- fold) of myostatin mRNA, another myokine that is a negative regulator of muscle hypertrophy and hyperplasia that impacts on body fat accumulation. This study implicates Rev-erbbeta in the control of lipid and energy homoeostasis in skeletal muscle. In conclusion, we speculate that selective modulators of Rev-erbbeta may have therapeutic utility in the treatment of dyslipidemia and regulation of muscle growth.

A CFTR chloride channel activator prevents HrpN(ea)-induced cell death in Arabidopsis thaliana suspension cells

Erwinia amylovora is a necrogenic bacterium that causes fire blight of the Maloideae subfamily of Roseacae, such as apple and pear. It provokes necrosis in aerial parts of susceptible host plants and the typical hypersensitive reaction in non-host plants. The secreted hatpin, HrpN(ea), is able by itself to induce an active cell death in non-host plants. Ion flux modulations were shown to be involved early in such processes but very few data are available on the plasma membrane ion channel activities responsible for the pathogen-induced ion fluxes. We show here that HrpNea induces cell death in non-host Arabidopsis thaliana suspension cells. We further show that two cystic fibrosis transmembrane conductance regulator modulators, glibenclamide and bromotetramisole, can regulate anion channel activities and HrpN(ea)-induced cell death. (c) 2005 Elsevier SAS. All rights reserved.

Continuous variable tripartite entanglement from twin nonlinearities

In this work, we analyse and compare the continuous variable tripartite entanglement available from the use of two concurrent or cascaded X (2) nonlinearities. We examine both idealized travelling-wave models and more experimentally realistic intracavity models, showing that tripartite entangled outputs are readily producible. These may be a useful resource for applications such as quantum cryptography and teleportation.

Entangled-state cycles from conditional quantum evolution

A system of cascaded qubits interacting via the one-way exchange of photons is studied. While for general operating conditions the system evolves to a superposition of Bell states (a dark state) in the long-time limit, under a particular resonance condition no steady state is reached within a finite time. We analyze the conditional quantum evolution (quantum trajectories) to characterize the asymptotic behavior under this resonance condition. A distinct bimodality is observed: for perfect qubit coupling, the system either evolves to a maximally entangled Bell state without emitting photons (the dark state) or executes a sustained entangled-state cycle-random switching between a pair of Bell states while emitting a continuous photon stream; for imperfect coupling, two entangled-state cycles coexist, between which a random selection is made from one quantum trajectory to another.

Prediction of protein continuum secondary structure with probabilistic models based on NMR solved structures

Background: The structure of proteins may change as a result of the inherent flexibility of some protein regions. We develop and explore probabilistic machine learning methods for predicting a continuum secondary structure, i.e. assigning probabilities to the conformational states of a residue. We train our methods using data derived from high-quality NMR models. Results: Several probabilistic models not only successfully estimate the continuum secondary structure, but also provide a categorical output on par with models directly trained on categorical data. Importantly, models trained on the continuum secondary structure are also better than their categorical counterparts at identifying the conformational state for structurally ambivalent residues. Conclusion: Cascaded probabilistic neural networks trained on the continuum secondary structure exhibit better accuracy in structurally ambivalent regions of proteins, while sustaining an overall classification accuracy on par with standard, categorical prediction methods.

Top-down influences on lexical selection during spoken word production: A 4T fMRI investigation of refractory effects in picture naming

Spoken word production is assumed to involve stages of processing in which activation spreads through layers of units comprising lexical-conceptual knowledge and their corresponding phonological word forms. Using high-field (4T) functional magnetic resonance imagine (fMRI), we assessed whether the relationship between these stages is strictly serial or involves cascaded-interactive processing, and whether central (decision/control) processing mechanisms are involved in lexical selection. Participants performed the competitor priming paradigm in which distractor words, named from a definition and semantically related to a subsequently presented target picture, slow picture-naming latency compared to that with unrelated words. The paradigm intersperses two trials between the definition and the picture to be named, temporally separating activation in the word perception and production networks. Priming semantic competitors of target picture names significantly increased activation in the left posterior temporal cortex, and to a lesser extent the left middle temporal cortex, consistent with the predictions of cascaded-interactive models of lexical access. In addition, extensive activation was detected in the anterior cingulate and pars orbitalis of the inferior frontal gyrus. The findings indicate that lexical selection during competitor priming is biased by top-down mechanisms to reverse associations between primed distractor words and target pictures to select words that meet the current goal of speech.

Toxin insights into nicotinic acetylcholine receptors

Venomous species have evolved cocktails of bioactive peptides to facilitate prey capture. Given their often exquisite potency and target selectivity, venom peptides provide unique biochemical tools for probing the function of membrane proteins at the molecular level. in the field of the nicotinic acetylcholine receptors (nAChRs), the subtype specific snake alpha-neurotoxins and cone snail alpha-conotoxins have been widely used to probe receptor structure and function in native tissues and recombinant systems. However, only recently has it been possible to generate an accurate molecular view of these nAChR-toxin interactions. Crystal structures of AChBP, a homologue of the nAChR ligand binding domain, have now been solved in complex with alpha-cobratoxin, alpha-conotoxin PnIA and alpha-conotoxin Iml. The orientation of all three toxins in the ACh binding site confirms many of the predictions obtained from mutagenesis and docking simulations on homology models of mammalian nAChR. The precise understanding of the molecular determinants of these complexes is expected to contribute to the development of more selective nAChR modulators. In this commentary, we review the structural data on nAChR-toxin interactions and discuss their implications for the design of novel ligands acting at the nAChR. (c) 2006 Elsevier Inc. All rights reserved.