A Selective PMCA Inhibitor Does Not Prolong the Electroolfactogram in Mouse

Within the cilia of vertebrate olfactory receptor neurons, Ca(2+) accumulates during odor transduction. Termination of the odor response requires removal of this Ca(2+), and prior evidence suggests that both Na(+)/Ca(2+) exchange and plasma membrane Ca(2+)-ATPase (PMCA) contribute to this removal.In intact mouse olfactory epithelium, we measured the time course of termination of the odor-induced field potential. Replacement of mucosal Na(+) with Li(+), which reduces the ability of Na(+)/Ca(2+) exchange to expel Ca(2+), prolonged the termination as expected. However, treating the epithelium with the specific PMCA inhibitor caloxin 1b1 caused no significant increase in the time course of response termination.Under these experimental conditions, PMCA does not contribute detectably to the termination of the odor response

Spatial Distribution of Calcium-Gated Chloride Channels in Olfactory Cilia

Background: In vertebrate olfactory receptor neurons, sensory cilia transduce odor stimuli into changes in neuronal membrane potential. The voltage changes are primarily caused by the sequential openings of two types of channel: a cyclic-nucleotide-gated (CNG) cationic channel and a calcium-gated chloride channel. In frog, the cilia are 25 to 200 mm in length, so the spatial distributions of the channels may be an important determinant of odor sensitivity. Principal Findings: To determine the spatial distribution of the chloride channels, we recorded from single cilia as calcium was allowed to diffuse down the length of the cilium and activate the channels. A computational model of this experiment allowed an estimate of the spatial distribution of the chloride channels. On average, the channels were concentrated in a narrow band centered at a distance of 29 % of the ciliary length, measured from the base of the cilium. This matches the location of the CNG channels determined previously. This non-uniform distribution of transduction proteins is consistent with similar findings in other cilia. Conclusions: On average, the two types of olfactory transduction channel are concentrated in the same region of the cilium

Polarizing Double Negation Translations

Double-negation translations are used to encode and decode classical proofs in intuitionistic logic. We show that, in the cut-free fragment, we can simplify the translations and introduce fewer negations. To achieve this, we consider the polarization of the formul{\ae}{} and adapt those translation to the different connectives and quantifiers. We show that the embedding results still hold, using a customized version of the focused classical sequent calculus. We also prove the latter equivalent to more usual versions of the sequent calculus. This polarization process allows lighter embeddings, and sheds some light on the relationship between intuitionistic and classical connectives

Limits of Calcium Clearance by Plasma Membrane Calcium ATPase in Olfactory Cilia

BACKGROUND: In any fine sensory organelle, a small influx of Ca(2+) can quickly elevate cytoplasmic Ca(2+). Mechanisms must exist to clear the ciliary Ca(2+) before it reaches toxic levels. One such organelle has been well studied: the vertebrate olfactory cilium. Recent studies have suggested that clearance from the olfactory cilium is mediated in part by plasma membrane Ca(2+)-ATPase (PMCA). PRINCIPAL FINDINGS: In the present study, electrophysiological assays were devised to monitor cytoplasmic free Ca(2+) in single frog olfactory cilia. Ca(2+) was allowed to enter isolated cilia, either through the detached end or through membrane channels. Intraciliary Ca(2+) was monitored via the activity of ciliary Ca(2+)-gated Cl(-) channels, which are sensitive to free Ca(2+) from about 2 to 10 microM. No significant effect of MgATP on intraciliary free Ca(2+) could be found. Carboxyeosin, which has been used to inhibit PMCA, was found to substantially increase a ciliary transduction current activated by cyclic AMP. This increase was ATP-independent. CONCLUSIONS: Alternative explanations are suggested for two previous experiments taken to support a role for PMCA in ciliary Ca(2+) clearance. It is concluded that PMCA in the cilium plays a very limited role in clearing the micromolar levels of intraciliary Ca(2+) produced during the odor response

Health-related quality of life among adult HIV positive patients : assessing comprehensive themes and interrelated associations

Acknowledgements We would like to thank all HIV doctors, HIV nurses and clinical nurse specialists for their help with the inclusion of patients in the study. We are further grateful to all patients who filled out the questionnaires.Peer reviewedPublisher PD

Correlating matched-filter model for analysis and optimisation of neural networks

A new formalism is described for modelling neural networks by means of which a clear physical understanding of the network behaviour can be gained. In essence, the neural net is represented by an equivalent network of matched filters which is then analysed by standard correlation techniques. The procedure is demonstrated on the synchronous Little-Hopfield network. It is shown how the ability of this network to discriminate between stored binary, bipolar codes is optimised if the stored codes are chosen to be orthogonal. However, such a choice will not often be possible and so a new neural network architecture is proposed which enables the same discrimination to be obtained for arbitrary stored codes. The most efficient convergence of the synchronous Little-Hopfield net is obtained when the neurons are connected to themselves with a weight equal to the number of stored codes. The processing gain is presented for this case. The paper goes on to show how this modelling technique can be extended to analyse the behaviour of both hard and soft neural threshold responses and a novel time-dependent threshold response is described

Chatbot Theory: A naïve and elementary theory for dialogue management

Due to the increasing interested and use of chatbot, its properties and operation possibilities shall be proper realized matching both safety and security issues as well as present the several uses and compositions that this technology supports. This paper focus is on dialogue management since it is considered the core of a chatbot. The dialogue manager is responsible to, more than to transform an input sentence into an output one, hold the illusion of a human conversation. In this sense, it is presented an inceptive theoretical framework through a formal way for chatbots that can be used as a reference to explore, compose, build and discuss chatbots. The discussion is performed mostly on ELIZA since, due to its historical records, it can be considered an important reference chatbot, nevertheless, the proposed theory is compatible with the most recent technologies such those using machine and deep learning. The paper then presents some sketchy instances in order to explore the support provided by the theory.This paper has been supported by COMPETE: POCI-01-0145-FEDER-0070 43 and FCT – Fundação para a Ciência e Tecnologia - Project UID/CEC/ 00319/2013

A coalgebraic view of bar recursion and bar induction

We reformulate the bar recursion and induction principles in terms of recursive and wellfounded coalgebras. Bar induction was originally proposed by Brouwer as an axiom to recover certain classically valid theorems in a constructive setting. It is a form of induction on non- wellfounded trees satisfying certain properties. Bar recursion, introduced later by Spector, is the corresponding function defnition principle. We give a generalization of these principles, by introducing the notion of barred coalgebra: a process with a branching behaviour given by a functor, such that all possible computations terminate. Coalgebraic bar recursion is the statement that every barred coalgebra is recursive; a recursive coalgebra is one that allows defnition of functions by a coalgebra-to-algebra morphism. It is a framework to characterize valid forms of recursion for terminating functional programs. One application of the principle is the tabulation of continuous functions: Ghani, Hancock and Pattinson defned a type of wellfounded trees that represent continuous functions on streams. Bar recursion allows us to prove that every stably continuous function can be tabulated to such a tree where by stability we mean that the modulus of continuity is also continuous. Coalgebraic bar induction states that every barred coalgebra is well-founded; a wellfounded coalgebra is one that admits proof by induction