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Incident detection is a key component in real-time traffic management systems that allows efficient response plan generation and decision making by means of risk alerts at critical affected sections in the network. State-of-the-art incident detection techniques traditionally require: i) good quality data from closely located sensor pairs, ii) a minimum of two reliable measurements from the flow- occupancy-speed triad, and iii) supervised adjustment of thresholds that will trigger anomalous traffic states. Despite such requirements may be reasonably achieved in simulated scenarios, real-time downstream applications rarely work under such ideal conditions and must deal with low reliability data, missing measurements, and scarcity of curated incident labelled datasets, among other challenges. This paper proposes an unsupervised technique based on univariate timeseries anomaly detection for computationally efficient incident detection in real-world scenarios. Such technique is proved to successfully work when only flow measurements are available, and to dynamically adjust thresholds that adapt to changes in the supply. Moreover, results show good performance with low-reliability and missing data.

Predicting future demand from the current state of the network is an unsolved challenge in dynamic traffic management systems which show the current state of traffic as well as demand and supply forecasts for simulations of response plans. In the context of the TANGENT H2020 project, data-driven methodologies are developed focusing on the real-time demand prediction problem.This paper presents a spatial-temporal graph attention network (ST-GAT) to model: 1) the geometry of the network including centroids as demand generation points; 2) the temporal resolution of traffic counts.Preliminary experiments show promising outcomes when quasi-perfect synthetic data is used for training. Yet more research is needed to fully cater for the challenging requirements of the demand prediction task in real-time settings.

ATP-citrate lyase (ACLY) is a key enzyme provoking metabolic and epigenetic gene regulation. Molecularly, these functions are exerted by the provision of acetyl-coenzyme A, which is then used as a substrate for de novo lipogenesis or as an acetyl-group donor in acetylation reactions. It has been demonstrated that ACLY activity can be positively regulated via phosphorylation at serine 455 by Akt and protein kinase A. Nonetheless, the impact of phosphorylation on ACLY function in human myeloid cells is poorly understood. In this study we reconstituted ACLY knockout human monocytic THP-1 cells with a wild type ACLY as well as catalytically inactive H760A, and phosphorylation-deficient S455A mutants. Using these cell lines, we determined the impact of ACLY activity and phosphorylation on histone acetylation and pro-inflammatory gene expression in response to lipopolysaccharide (LPS). Our results show that ACLY serine 455 phosphorylation does not influence the proper enzymatic function of ACLY, since both, wild type ACLY and phosphorylation-deficient mutant, exhibited increased cell growth and histone acetylation as compared to cells with a loss of ACLY activity. Transcriptome analysis revealed enhanced expression of pro-inflammatory and interferon response genes in ACLY knockout and H760A THP-1 cells under unstimulated or LPS-treated conditions. At the same time, S455A ACLY-expressing cells showed a phenotype very similar to wild type cells. Contrary to ACLY knockout, pharmacological inhibition of ACLY in THP-1 cells or in primary human macrophages does not enhance LPS-triggered pro-inflammatory gene expression. Our data thus suggest that ACLY retains functionality in the absence of Akt/PKA-mediated phosphorylation in human myeloid cells. Furthermore, loss of ACLY activity may elicit long-term adaptive mechanisms, increasing inflammatory responses.

Studies over the past decade have revealed that metabolism profoundly influences immune responses. In particular, metabolism causes epigenetic regulation of gene expression, as a growing number of metabolic intermediates are substrates for histone post-translational modifications altering chromatin structure. One of these substrates is acetyl-coenzyme A (CoA), which donates an acetyl group for histone acetylation. Cytosolic acetyl-CoA is also a critical substrate for de novo synthesis of fatty acids and sterols necessary for rapid cellular growth. One of the main enzymes catalyzing cytosolic acetyl-CoA formation is ATP-citrate lyase (ACLY). In addition to its classical function in the provision of acetyl-CoA for de novo lipogenesis, ACLY contributes to epigenetic regulation through histone acetylation, which is increasingly appreciated. In this review we explore the current knowledge of ACLY and acetyl-CoA in mediating innate and adaptive immune responses. We focus on the role of ACLY in supporting de novo lipogenesis in immune cells as well as on its impact on epigenetic alterations. Moreover, we summarize alternative sources of acetyl-CoA and their contribution to metabolic and epigenetic regulation in cells of the immune system.

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A fraction of procyanidin (PC) was purified from the cider apple and used as the sole carbon source in order to evaluate the potency of different filamentous fungi to grow and degrade them. Fiftegn filamentous fungi were screened in a mineral medium with or without glucose. Almost all the strains were observed to have PC degradation ability. Aspergillus fumigatus was the most efficient fungus that degraded >5OVo of PC after 72h of growth. This strain was selected for further studies. The PC cultured samples were analyzed by thiolysis-HPlC method and constitutive units (catechin units) ofPC polymer were quantified and characterized. Kinetics ofPC degradation revealed that the terminal units of PC decreased during fermentation and on the contrary, an increase in the average degree of polymerization (DPn) from 8 to 36 was also observed at the end of fermentation. These findings suggested that terminal units were possibly modifred by the enzymatic action of the fungus. Normal-Phase HPLC analysis showed that PC oligomers were degraded during the early phase

International audience; Aspergillus fumigatus was able to grow on apple-purified procyanidins (PCs). PCs concentration decreased 30% over the first 60 h of liquid fermentation. The mean degree of polymerization (DPn) of apple-purified PCs increased from 8 to 15 during the fermentation. A fungal enzyme extract from the liquid fermentation was used to study procyanidin B2 [( )-epicatechin-(4b-8)-( )-epicatechin] degradation. The major degradation product (PB2-X) had a retention time of 10.5 min and a molecular mass at m/z 609. High-performance liquid chromatography/multiple fragment mass spectrometry (HPLC/MSn) was used for the structural characterization of PB2-X as well as that of thiolysis-treated PB2-X. Twelve fragment ions at m/z 565, 547, 457, 439 (two fragment ions), 421, 413, 377, 395, 351, 287 and 277 were completely identified. It was therefore deduced that the terminal unit of procyanidin B2 dimer was modified by an oxygenase from A. fumigatus leaving the extension unit intact. In addition, FT-IR analysis confirmed a lactone formation in ( )-epicatechin moiety involved in oxidative degradation. Two reaction schemes were postulated for the interpretation of the results.

[This corrects the article DOI: 10.3389/fimmu.2022.906127.]., (Copyright © 2024 Dominguez, Truemper, Mota, Brüne and Namgaladze.)