Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission

"Diffuse" gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived "average" spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S. Cheng and G. E. Romero. More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Grid-texture mechanisms in human vision:contrast detection of regular sparse micro-patterns requires specialist templates

Previous work has shown that human vision performs spatial integration of luminance contrast energy, where signals are squared and summed (with internal noise) over area at detection threshold. We tested that model here in an experiment using arrays of micro-pattern textures that varied in overall stimulus area and sparseness of their target elements, where the contrast of each element was normalised for sensitivity across the visual field. We found a power-law improvement in performance with stimulus area, and a decrease in sensitivity with sparseness. While the contrast integrator model performed well when target elements constituted 50–100% of the target area (replicating previous results), observers outperformed the model when texture elements were sparser than this. This result required the inclusion of further templates in our model, selective for grids of various regular texture densities. By assuming a MAX operation across these noisy mechanisms the model also accounted for the increase in the slope of the psychometric function that occurred as texture density decreased. Thus, for the first time, mechanisms that are selective for texture density have been revealed at contrast detection threshold. We suggest that these mechanisms have a role to play in the perception of visual textures

Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention

Aim: A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results: The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91–209) vs. 134 (85–194) AU⋅min, P 203 AU⋅min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08–2.68; P = 0.02). Bleeding risk was not altered. Conclusion: We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated

Exploiting Ligand-Protein Conjugates to Monitor Ligand-Receptor Interactions

We introduce three assays for analyzing ligand-receptor interactions based on the specific conjugation of ligands to SNAP-tag fusion proteins. Conjugation of ligands to different SNAP-tag fusions permits the validation of suspected interactions in cell extracts and fixed cells as well as the establishment of high-throughput assays. The different assays allow the analysis of strong and weak interactions. Conversion of ligands into SNAP-tag substrates thus provides access to a powerful toolbox for the analysis of their interactions with proteins

Four theorems on the psychometric function

In a 2-alternative forced-choice (2AFC) discrimination task, observers choose which of two stimuli has the higher value. The psychometric function for this task gives the probability of a correct response for a given stimulus difference, Δx. This paper proves four theorems about the psychometric function. Assuming the observer applies a transducer and adds noise, Theorem 1 derives a convenient general expression for the psychometric function. Discrimination data are often fitted with a Weibull function. Theorem 2 proves that the Weibull "slope" parameter, β, can be approximated by [Formula: see text], where [Formula: see text] is the β of the Weibull function that fits best to the cumulative noise distribution, and [Formula: see text] depends on the transducer. We derive general expressions for [Formula: see text] and [Formula: see text], from which we derive expressions for specific cases. One case that follows naturally from our general analysis is Pelli's finding that, when [Formula: see text], [Formula: see text]. We also consider two limiting cases. Theorem 3 proves that, as sensitivity improves, 2AFC performance will usually approach that for a linear transducer, whatever the actual transducer; we show that this does not apply at signal levels where the transducer gradient is zero, which explains why it does not apply to contrast detection. Theorem 4 proves that, when the exponent of a power-function transducer approaches zero, 2AFC performance approaches that of a logarithmic transducer. We show that the power-function exponents of 0.4-0.5 fitted to suprathreshold contrast discrimination data are close enough to zero for the fitted psychometric function to be practically indistinguishable from that of a log transducer. Finally, Weibull β reflects the shape of the noise distribution, and we used our results to assess the recent claim that internal noise has higher kurtosis than a Gaussian. Our analysis of β for contrast discrimination suggests that, if internal noise is stimulus-independent, it has lower kurtosis than a Gaussian

Neonatal Fc Receptor: From Immunity to Therapeutics

The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn