Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation

Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the molecular phenotype of these cells; previous attempts at comprehensive profiling had only limited sensitivity or were inaccurate. We generated a Hcrt translating ribosome affinity purification (bacTRAP) line for comprehensive translational profiling of all ribosome-bound transcripts in these neurons in vivo. From this profile, we identified >6000 transcripts detectably expressed above background and 188 transcripts that are highly enriched in these neurons, including all known markers of the cells. Blinded analysis of in situ hybridization databases suggests that ∼60% of these are expressed in a Hcrt marker-like pattern. Fifteen of these were confirmed with double labeling and microscopy, including the transcription factor Lhx9. Ablation of this gene results in a >30% loss specifically of Hcrt neurons, without a general disruption of hypothalamic development. Polysomnography and activity monitoring revealed a profound hypersomnolence in these mice. These data provide an in-depth and accurate profile of Hcrt neuron gene expression and suggest that Lhx9 may be important for specification or survival of a subset of these cells

ImageCLEF 2020: Multimedia Retrieval in Lifelogging, Medical, Nature, and Security Applications

This paper presents an overview of the 2020 ImageCLEF lab that will be organized as part of the Conference and Labs of the Evaluation Forum - CLEF Labs 2020 in Thessaloniki, Greece. ImageCLEF is an ongoing evaluation initiative (run since 2003) that promotes the evaluation of technologies for annotation, indexing and retrieval of visual data with the aim of providing information access to large collections of images in various usage scenarios and domains. In 2020, the 18th edition of ImageCLEF will organize four main tasks: (i) a Lifelog task (videos, images and other sources) about daily activity understanding, retrieval and summarization, (ii) a Medical task that groups three previous tasks (caption analysis, tuberculosis prediction, and medical visual question answering) with new data and adapted tasks, (iii) a Coral task about segmenting and labeling collections of coral images for 3D modeling, and a new (iv) Web user interface task addressing the problems of detecting and recognizing hand drawn website UIs (User Interfaces) for generating automatic code. The strong participation, with over 235 research groups registering and 63 submitting over 359 runs for the tasks in 2019 shows an important interest in this benchmarking campaign. We expect the new tasks to attract at least as many researchers for 2020

Oleic Acid Biosynthesis in Plasmodium falciparum: Characterization of the Stearoyl-CoA Desaturase and Investigation as a Potential Therapeutic Target

BACKGROUND:Plasmodium falciparum parasitization of erythrocytes causes a substantial increase in the levels of intracellular fatty acids, notably oleic acid. How parasites acquire this monounsaturated fatty acid has remained enigmatic. Here, we report on the biochemical and enzymatic characterization of stearoyl-CoA desaturase (SCD) in P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS:Metabolic labeling experiments allowed us to demonstrate the production of oleic acid from stearic acid both in lysates of parasites incubated with [(14)C]-stearoyl-CoA and in parasite-infected erythrocytes labeled with [(14)C]-stearic acid. Optimal SCD activity was detected in schizonts, the stage of maximal membrane synthesis. This activity correlated with a late trophozoite stage-specific induction of PFE0555w transcripts. PFE0555w harbors a typical SCD signature. Similar to mammalian SCDs, this protein was found to be associated with the endoplasmic reticulum, as determined with PFE0555w-GFP tagged transgenic P. falciparum. Importantly, these parasites exhibited increased rates of stearic to oleic acid conversion, providing additional evidence that PFE0555w encodes the plasmodial SCD (PfSCD). These findings prompted us to assess the activity of sterculic acid analogues, known to be specific Delta9-desaturase inhibitors. Methyl sterculate inhibited the synthesis of oleic acid both with parasite lysates and infected erythrocytes, most likely by targeting PfSCD. This compound exhibited significant, rapid and irreversible antimalarial activity against asexual blood stages. This parasiticidal effect was antagonized by oleic acid. CONCLUSION/SIGNIFICANCE:Our study provides evidence that parasite-mediated fatty acid modification is important for blood-stage survival and provides a new strategy to develop a novel antimalarial therapeutic based on the inhibition of PfSCD

The 2021 ImageCLEF Benchmark: Multimedia Retrieval in Medical, Nature, Internet and Social Media Applications

This paper presents the ideas for the 2021 ImageCLEF lab that will be organized as part of the Conference and Labs of the Evaluation Forum — CLEF Labs 2021 in Bucharest, Romania. ImageCLEF is an ongoing evaluation initiative (active since 2003) that promotes the evaluation of technologies for annotation, indexing and retrieval of visual data with the aim of providing information access to large collections of images in various usage scenarios and domains. In 2021, the 19th edition of ImageCLEF will organize four main tasks: (i) a Medical task addressing visual question answering, a concept annotation and a tuberculosis classification task, (ii) a Coral task addressing the annotation and localisation of substrates in coral reef images, (iii) a DrawnUI task addressing the creation of websites from either a drawing or a screenshot by detecting the different elements present on the design and a new (iv) Aware task addressing the prediction of real-life consequences of online photo sharing. The strong participation in 2020, despite the COVID pandemic, with over 115 research groups registering and 40 submitting over 295 runs for the tasks shows an important interest in this benchmarking campaign. We expect the new tasks to attract at least as many researchers for 2021

Overview of the ImageCLEF 2021: Multimedia Retrieval in Medical, Nature, Internet and Social Media Applications

This paper presents an overview of the ImageCLEF 2021 lab that was organized as part of the Conference and Labs of the Evaluation Forum – CLEF Labs 2021. ImageCLEF is an ongoing evaluation initiative (first run in 2003) that promotes the evaluation of technologies for annotation, indexing and retrieval of visual data with the aim of providing information access to large collections of images in various usage scenarios and domains. In 2021, the 19th edition of ImageCLEF runs four main tasks: (i) a medical task that groups three previous tasks, i.e., caption analysis, tuberculosis prediction, and medical visual question answering and question generation, (ii) a nature coral task about segmenting and labeling collections of coral reef images, (iii) an Internet task addressing the problems of identifying hand-drawn and digital user interface components, and (iv) a new social media aware task on estimating potential real-life effects of online image sharing. Despite the current pandemic situation, the benchmark campaign received a strong participation with over 38 groups submitting more than 250 runs

Creating and curating an archive: Bury St Edmunds and its Anglo-Saxon past

This contribution explores the mechanisms by which the Benedictine foundation of Bury St Edmunds sought to legitimise and preserve their spurious pre-Conquest privileges and holdings throughout the Middle Ages. The archive is extraordinary in terms of the large number of surviving registers and cartularies which contain copies of Anglo-Saxon charters, many of which are wholly or partly in Old English. The essay charts the changing use to which these ancient documents were put in response to threats to the foundation's continued enjoyment of its liberties. The focus throughout the essay is to demonstrate how pragmatic considerations at every stage affects the development of the archive and the ways in which these linguistically challenging texts were presented, re-presented, and represented during the Abbey’s history

VisionAPI: An API for Offline and Online Segmentation and Identification of Hand-Sketched Graphical User Interfaces

Segmentation and identification of a graphical user interface consist of detecting the location, dimensions, and arrangement of elements of the user interface, such as controls, labels, images, and icons, and recognizing them, respectively. While these problems have been already addressed for a graphical user interface stored in a file and processed offline, it has received less attention for online processing when the interface evolves and is expressed in different formats, such as a whiteboard drawing or a paper sketch. To overcome these limitations, we present VisionAPI, an application programming interface trained for segmenting and identifying elements of a hand-sketched graphical user interface both offline and online using computer vision. For this purpose, we rely on a software architecture based on Resnet101 to extract features and Faster R-CNN to build boundary boxes to obtain an 85% recognition rate for 21 classes of elements found in graphical user interfaces: paragraph, dropdown list, checkbox, radio button, rating, toggle button, text area, date picker, stepper input, slider, video, label, table, list, header, button, image, linebreak, container, link, and text input

Evaluating a Large Language Model on Searching for GUI Layouts

The field of generative artificial intelligence has seen significant advancements in recent years with the advent of large language models, which have shown impressive results in software engineering tasks but not yet in engineering user interfaces. Thus, we raise a specific research question: would an LLM-based system be able to search for relevant GUI layouts? To address this question, we conducted a controlled study evaluating how Instigator, an LLM-based system for searching GUI layouts of web pages by generative pre-trained training, would return GUI layouts that are relevant to a given instruction and what would be the user experience of (N=34) practitioners interacting with Instigator. Our results identify a very high similarity and a moderate correlation between the rankings of the GUI layouts generated by Instigator and the rankings of the practitioners with respect to their relevance to a given design instruction. We highlight the results obtained through thirteen UEQ+ scales that characterize the user experience of the practitioner with Instigator, which we use to discuss perspectives for improving such future tool

Dynamics of ozone and nitrogen oxides at Summit, Greenland: I. Multi-year observations in the snowpack

© 2015 Elsevier Ltd. A multi-year investigation of ozone (O3) and nitrogen oxides (NOx) in snowpack interstitial air down to a depth of 2.8 m was conducted at Summit, Greenland, to elucidate mechanisms controlling the production and destruction of these important trace gases within the snow. Snowpack O3 values ranged from 30 to 40 ppbv during winter months, and dropped below 10 ppbv in summer. Wintertime NOx levels were low at all depths in the snowpack (below 10 pptv for NO and below 25 pptv for NO2). In the summer, NO values up to 120 pptv, and NO2 mixing ratios up to ∼700 pptv were observed. O3 loss within the snowpack was observed throughout all seasons. The magnitude of the O3 loss rate tracked the seasonal and diurnal cycle of incoming short wave solar radiation. Production of NO within a shallow layer of the snowpack was recorded during the spring and summer months. NO2 production also occurred, and heightened levels were measured down to 2.5 m in the snowpack. The average daily maximum in NO was observed at solar noon, and the minimum was seen during night. The daily peak in NO2 was on average 7 h shifted from the incoming solar radiation and NO maxima. NOx levels in interstitial air during spring were enhanced relative to summer and fall. The influence of meteorological effects such as wind pumping on snowpack interstitial air levels of O3 and NOx was investigated using case study periods. Increased snowpack ventilation during high wind events was found to yield enhancement in snowpack NOx, with this effect being enhanced during times when O3 was elevated in ambient air. This behavior suggests that O3 is involved in NOx production in the snowpack. This extensive set of observations is used to re-evaluate physical and chemical processes that describe the dynamic O3 and NOx chemistry occurring within snowpack interstitial air at Summit