Registration of retinal images from Public Health by minimising an error between vessels using an affine model with radial distortions

In order to estimate a registration model of eye fundus images made of an affinity and two radial distortions, we introduce an estimation criterion based on an error between the vessels. In [1], we estimated this model by minimising the error between characteristics points. In this paper, the detected vessels are selected using the circle and ellipse equations of the overlap area boundaries deduced from our model. Our method successfully registers 96 % of the 271 pairs in a Public Health dataset acquired mostly with different cameras. This is better than our previous method [1] and better than three other state-of-the-art methods. On a publicly available dataset, ours still better register the images than the reference method

Cyber Enigmas? Passive Detection and Pedagogical Agents: Can Students Spot the Fake?

This paper presents a study that was undertaken to examine human interaction with a pedagogical agent and the passive and active detection of such agents within a synchronous, online environment. A pedagogical agent is a software application which can provide a human like interaction using a natural language interface. These may be familiar from the smartphone interfaces such as ‘Siri’ or ‘Cortana’, or the virtual online assistants found on some websites, such as ‘Anna’ on the Ikea website. Pedagogical agents are characters on the computer screen with embodied life-like behaviours such as speech, emotions, locomotion, gestures, and movements of the head, the eye, or other parts of the body. The passive detection test is where participants are not primed to the potential presence of a pedagogical agent within the online environment. The active detection test is where participants are primed to the potential presence of a pedagogical agent. The purpose of the study was to examine how people passively detected pedagogical agents that were presenting themselves as humans in an online environment. In order to locate the pedagogical agent in a realistic higher education online environment, problem-based learning online was used. Problem-based learning online provides a focus for discussions and participation, without creating too much artificiality. The findings indicated that the ways in which students positioned the agent tended to influence the interaction between them. One of the key findings was that since the agent was focussed mainly on the pedagogical task this may have hampered interaction with the students, however some of its non-task dialogue did improve students' perceptions of the autonomous agents’ ability to interact with them. It is suggested that future studies explore the differences between the relationships and interactions of learner and pedagogical agent within authentic situations, in order to understand if students' interactions are different between real and virtual mentors in an online setting

Association analysis in Kabuli chickpea (Cicer arietinum L.)

In the millennium of an ever-growing population, feeding the millions ample amount of food with necessarily required nutrition has become a tough challenge. To cater protein requirement, plant-based protein, especially pulses, have always been a better option. Among the pulses, chickpea is one of the choicest crops being extensively cultivated throughout the world. However, the production and productivity of crops are not sufficient to meet consumer demand throughout the world. To aid in the selection process of chickpea breeding, the present study was performed to evaluate fifty-one kabuli chickpea (Cicer arietinum L.) germplasm lines along with four checks for the degree and direction of association of twelve quantitative characters on yield in fifty five kabuli chickpea genotypes. Considerable positive correlation was found between the weight of 100 seeds and the height of the chickpea plant, but the number of pods per plant and seed volume per weight were observed to be in negative association with the former trait. The primary branch depicted a substantial amount of positive correlation with harvest index, seed yield per individual plant, pods produced per plant. Secondly, the current study on association analysis also unveiled positive and highly significant correlations of the number of primary branches, height at the first pod set, pods/plant, and weight of 100 seeds on seed yield, suggesting their further use as selection criteria  in the  process of crop improvement

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

Objectives: Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species. Methods: The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target. Results: IBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target. Conclusions: The HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the 2-arylpropanoic class. Activity against stationary phase bacilli and multidrug-resistant isolates permits us to speculate a novel mechanism of antimycobacterial action. Further medicinal chemistry and target elucidation studies could potentially lead to new therapies against TB

Searching for pulsars associated with the Fermi GeV excess

The Fermi Large Area Telescope has detected an extended region of GeV emission towards the Galactic Centre that is currently thought to be powered by dark matter annihilation or a population of young and/or millisecond pulsars. In a test of the pulsar hypothesis, we have carried out an initial search of a 20 deg2 area centred on the peak of the galactic centre GeV excess. Candidate pulsars were identified as a compact, steep spectrum continuum radio source on interferometric images and followed with targeted single-dish pulsation searches. We report the discovery of the recycled pulsar PSR 1751−2737 with a spin period of 2.23 ms. PSR 1751−2737 appears to be an isolated recycled pulsar located within the disc of our Galaxy, and it is not part of the putative bulge population of pulsars that are thought to be responsible for the excess GeV emission. However, our initial success in this small pilot survey suggests that this hybrid method (i.e. wide-field interferometric imaging followed up with single-dish pulsation searches) may be an efficient alternative strategy for testing whether a putative bulge population of pulsars is responsible for the GeV excess

Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell wall peptidoglycan in Mycobacterium tuberculosis.

ATP-dependent Mur ligases (Mur synthetases) play essential roles in the biosynthesis of cell wall peptidoglycan (PG) as they catalyze the ligation of key amino acid residues to the stem peptide at the expense of ATP hydrolysis, thus representing potential targets for antibacterial drug discovery. In this study we characterized the division/cell wall (dcw) operon and identified a promoter driving the co-transcription of mur synthetases along with key cell division genes such as ftsQ and ftsW. Furthermore, we have extended our previous investigations of MurE to MurC, MurD and MurF synthetases from Mycobacterium tuberculosis. Functional analyses of the pure recombinant enzymes revealed that the presence of divalent cations is an absolute requirement for their activities. We also observed that higher concentrations of ATP and UDP-sugar substrates were inhibitory for the activities of all Mur synthetases suggesting stringent control of the cytoplasmic steps of the peptidoglycan biosynthetic pathway. In line with the previous findings on the regulation of mycobacterial MurD and corynebacterial MurC synthetases via phosphorylation, we found that all of the Mur synthetases interacted with the Ser/Thr protein kinases, PknA and PknB. In addition, we critically analyzed the interaction network of all of the Mur synthetases with proteins involved in cell division and cell wall PG biosynthesis to re-evaluate the importance of these key enzymes as novel therapeutic targets in anti-tubercular drug discovery

Roman mining on Exmoor: a geomorphological approach at Anstey's Combe, Dulverton

A survey of valley fills in south-facing combes (headwater valleys) along the south side of the Exmoor massif revealed an anomalously deep infill in one valley. This infill of up to 5 m depth had been gullied revealing a complex stratigraphy. Studies of the stratigraphy, clast orientation and shape suggested several accumulation episodes under different environmental conditions commencing in a periglacial climatic regime. Later units included sandy silts which can be dated using optically stimulated luminescence (OSL) of quartz grains. The OSL dates, indicate that the inter-gravel silts accumulated in two periods, the Romano-British period and the 16th-17th centuries AD. A survey of the very small valley catchment revealed a linear trench of a type associated with early iron mining. Given the anomalously high volume of accumulated sediment from such a small catchment and evidence of mining on the slope above the site, the geomorphic mechanism is almost certainly the downslope transport of mining debris from the slope to the valley floor. This study suggests that the systematic survey of headwater valleys in metalliferous uplands may be one way of locating areas of early mining activity and that such deposits could provide a chronology of working and abandonment

Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase

© 2018 Elsevier Ltd Multi-target inhibitors have become increasing popular as a means to leverage the advantages of poly-pharmacology while simplifying drug delivery. Here, we describe dual inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH), two targets known to synergize when treating inflammatory and neuropathic pain. The structure activity relationship (SAR) study described herein initially started with t-TUCB (trans-4-[4-(3-trifluoromethoxyphenyl-l-ureido)-cyclohexyloxy]-benzoic acid), a potent sEH inhibitor that was previously shown to weakly inhibit FAAH. Inhibitors with a 6-fold increase of FAAH potency while maintaining high sEH potency were developed by optimization. Interestingly, compared to most FAAH inhibitors that inhibit through time-dependent covalent modification, t-TUCB and related compounds appear to inhibit FAAH through a time-independent, competitive mechanism. These inhibitors are selective for FAAH over other serine hydrolases. In addition, FAAH inhibition by t-TUCB appears to be higher in human FAAH over other species; however, the new dual sEH/FAAH inhibitors have improved cross-species potency. These dual inhibitors may be useful for future studies in understanding the therapeutic application of dual sEH/FAAH inhibition