Interactions of chemostimuli at the single cell level: studies in a model system

The responses of afferent chemosensory fibres of the carotid body to individual chemostimuli have long been established. However, the mechanisms underlying the multiplicative interactions of these stimuli (i.e. how the combined effects of hypoxia and hypercapnia exert a greater effect on afferent nerve discharge than the sum of their individual effects) have not been elucidated. Using the membrane hypothesis for carotid body chemoreception, in which chemostimuli inhibit type I cell K+ channels, leading to depolarization, voltage-gated Ca2+ entry and hence the triggering of exocytosis, this article considers data acquired in isolated type I carotid body cells and model chemoreceptor (PC12) cells to attempt to explain stimulus interactions. Whilst stimulus interactions are not clearly evident at the level of K+ channel inhibition or rises of [Ca2+](i), they are apparent at the level of transmitter release. Thus, it is clear that individual chemoreceptor cells can sense multiple stimuli, and that interactions of these stimuli can produce greater than additive effects in terms of transmitter release

Hypoxic regulation of ion channel function and expression

Acute hypoxia regulates the activity of specific ion channels in a rapid and reversible manner. Such effects underlie appropriate cellular responses to hypoxia which are designed to initiate cardiorespiratory reflexes and contribute importantly to other tissue responses, all of which are designed to improve tissue O2 supply. These responses include excitation of chemoreceptors as well as pulmonary vasoconstriction and systemic vasodilatation. However, such responses may also contribute to the adverse responses to hypoxia, such as excitotoxicity in the central nervous system. Whilst numerous ion channel types are known to be modulated by acute hypoxia, the nature of the O2 sensor in most tissues remains to be identified. Prolonged (chronic) hypoxia regulates functional expression of ion channels, and so remodels excitability of various cell types. Whilst this may contribute to adaptive responses such as high-altitude acclimatization, such altered channel expression may also contribute to the onset of pathological disorders, including Alzheimer's disease. Indeed, evidence is emerging that production of pathological peptides associated with Alzheimer's disease is increased during prolonged hypoxia. Such effects may account for the known increased incidence of this disease in patients who have previously endured hypoxic episodes, such as congestive heart failure and stroke. Identification of the mechanisms coupling hypoxia to the increased production of these peptides is likely to be of therapeutic benefit

Acute oxygen sensing: diverse but convergent mechanisms in airway and arterial chemoreceptors

Airway neuroepithelial bodies sense changes in inspired O2, whereas arterial O2 levels are monitored primarily by the carotid body. Both respond to hypoxia by initiating corrective cardiorespiratory reflexes, thereby optimising gas exchange in the face of a potentially deleterious O2 supply. One unifying theme underpinning chemotransduction in these tissues is K+ channel inhibition. However, the transduction components, from O2 sensor to K+ channel, display considerable tissue specificity yet result in analogous end points. Here we highlight how emerging data are contributing to a more complete understanding of O2 chemosensing at the molecular level

Modeling Surface Appearance from a Single Photograph using Self-augmented Convolutional Neural Networks

We present a convolutional neural network (CNN) based solution for modeling physically plausible spatially varying surface reflectance functions (SVBRDF) from a single photograph of a planar material sample under unknown natural illumination. Gathering a sufficiently large set of labeled training pairs consisting of photographs of SVBRDF samples and corresponding reflectance parameters, is a difficult and arduous process. To reduce the amount of required labeled training data, we propose to leverage the appearance information embedded in unlabeled images of spatially varying materials to self-augment the training process. Starting from an initial approximative network obtained from a small set of labeled training pairs, we estimate provisional model parameters for each unlabeled training exemplar. Given this provisional reflectance estimate, we then synthesize a novel temporary labeled training pair by rendering the exact corresponding image under a new lighting condition. After refining the network using these additional training samples, we re-estimate the provisional model parameters for the unlabeled data and repeat the self-augmentation process until convergence. We demonstrate the efficacy of the proposed network structure on spatially varying wood, metals, and plastics, as well as thoroughly validate the effectiveness of the self-augmentation training process.Comment: Accepted to SIGGRAPH 201

Beware of Courts Bearing Gifts: Transparency and the Court of Justice of the European Union

This article reconsiders the principle of transparency in the European Union (EU) legal order and takes as its focal point the contribution of the EU Courts as regards the presumptions of non-disclosure of EU documents. The aim is to investigate the role played by the judiciary in relation to a twofold question: How open can the Union’s decision-making be, and is it possible for citizens to participate in the decision-making process of EU institutions, bodies, offices and agencies? The article argues that accountability deficits in the field of access to documents have been filled, to an extent, by the EU Courts’ imposition of boundaries on the broad derogations to the right of access to documents. But nevertheless, the article concludes that the establishment through the case law of general presumptions against openness has fundamentally weakened the standards of accountability. Rather regrettably, although the EU legislature set the default position to the widest access to documents, this has been reversed to non-disclosure by the EU judiciary as regards non-legislative documents

Irregular Migrants: Can Humane Treatment be Balanced against Efficient Removal?

The controversial Returns Directive has now been the subject of considerable jurisprudence of the CJEU, addressing many important issues of interpretation. This paper assesses whether the CJEU has been successful in its apparent attempts to balance humanitarian concerns with the EU legislator’s apparent objective of removing irregular migrants from the territory as quickly as possible

Reading the small print: will Cameron’s EU migration reforms pass legal muster?

The draft renegotiation deal obtained by David Cameron would amend three EU laws relating to migration: the free movement of citizens, their right to seek work in another Member State, and their right to claim social security benefits. Steve Peers explains what the proposals will mean and looks at whether they may be liable to legal challenge. He concludes that other Member States will probably accept the amendments on family members and may agree to the child benefit reforms, but the changes on in-work benefits are highly vulnerable