Pattern-based identity signatures are commonplace in the animal kingdom, but how they are recognized is poorly understood. Here we develop a computer vision tool for analysing visual patterns, NATUREPATTERNMATCH, which breaks new ground by mimicking visual and cognitive processes known to be involved in recognition tasks. We apply this tool to a long-standing question about the evolution of recognizable signatures. The common cuckoo (Cuculus canorus) is a notorious cheat that sneaks its mimetic eggs into nests of other species. Can host birds fight back against cuckoo forgery by evolving highly recognizable signatures? Using NATUREPATTERNMATCH, we show that hosts subjected to the best cuckoo mimicry have evolved the most recognizable egg pattern signatures. Theory predicts that effective pattern signatures should be simultaneously replicable, distinctive and complex. However, our results reveal that recognizable signatures need not incorporate all three of these features. Moreover, different hosts have evolved effective signatures in diverse ways.

Telaprevir 2 (VX-950), an inhibitor of the hepatitis C virus (HCV(a)) NS3-4A protease, is in phase 3 clinical trials. One of the major metabolites of 2 is its P1-(R)-diastereoisomer, 3 (VRT-394), containing an inversion at the chiral center next to the alpha-ketoamide on exchange of a proton with solvent. Compound 3 is approximately 30-fold less active against HCV protease. In an attempt to suppress the epimerization of 2 without losing activity against the HCV protease, the proton at that chiral site was replaced with deuterium (d). The compound 1 (d-telaprevir) is as efficacious as 2 in in vitro inhibition of protease activity and viral replication (replicon) assays. The kinetics of in vitro stability of 1 and 2 in buffered pH solutions and plasma samples, including human plasma, suggest that 1 is significantly more stable than 2. Oral administration (10 mg/kg) in rats resulted in a approximately 13% increase of AUC for 1.

For species which bear unique markings, such as natural spot patterning, field work has become increasingly more reliant on visual identification to recognize and catalog particular specimens or to monitor individuals within populations. While many species of interest exhibit characteristic markings that in principle allow individuals to be identified from photographs, scientists are often faced with the task of matching observations against databases of hundreds or thousands of images. We present a novel technique for automated identification of manta rays (Manta alfredi and Manta birostris) by means of a pattern-matching algorithm applied to images of their ventral surface area. Automated visual identification has recently been developed for several species. However, such methods are typically limited to animals that can be photographed above water, or whose markings exhibit high contrast and appear in regular constellations. While manta rays bear natural patterning across their ventral surface, these patterns vary greatly in their size, shape, contrast, and spatial distribution. Our method is the first to have proven successful at achieving high matching accuracies on a large corpus of manta ray images taken under challenging underwater conditions. Our method is based on automated extraction and matching of keypoint features using the Scale-Invariant Feature Transform (SIFT) algorithm. In order to cope with the considerable variation in quality of underwater photographs, we also incorporate preprocessing and image enhancement steps. Furthermore, we use a novel pattern-matching approach that results in better accuracy than the standard SIFT approach and other alternative methods. We present quantitative evaluation results on a data set of 720 images of manta rays taken under widely different conditions. We describe a novel automated pattern representation and matching method that can be used to identify individual manta rays from photographs. The method has been incorporated into a website (mantamatcher.org) which will serve as a global resource for ecological and conservation research. It will allow researchers to manage and track sightings data to establish important life-history parameters as well as determine other ecological data such as abundance, range, movement patterns, and structure of manta ray populations across the world.

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Abstract

While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.

1. 14C-labelled 1-aminobenzotriazole (ABT), a suicide inactivator of cytochrome P450, was synthesized and administered orally to male rats. The rats were killed at 1, 6, 24, 48 or 72 h after dosing and the concentration of total radioactivity in various tissues and organs measured. 2. The compound appears to be absorbed slowly with 50% of the radioactivity remaining in the stomach at 6 h after dosing and maximum plasma and tissue concentrations were observed at 24 h. 3. Approximately 71% of the dose of 14C was excreted in the urine and 12% in the faeces over 72 h, indicating oral absorption of at least 71%. Tissue-to-plasma ratios of 14C were highest in the liver, adrenals and kidneys, which all contain significant amounts of cytochrome P450; the half-lives of elimination for total 14C in liver, adrenals and kidneys were approximately 24, 16 and 12 h, respectively, while the half-life in plasma was approximately 9 h. 4. ABT was metabolized by N-acetylation, with the acetylated product attaining concentrations equal to ABT in the plasma; two other major metabolites were also excreted in the urine namely, the N-glucuronide of 1-aminobenzotriazole and the N-glucuronide of benzotriazole.

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