Charting arabidopsis gene functions from multi-omics and single-cell data

Het ontrafelen van gen functie en regulatie is cruciaal voor het begrijpen van de signaalcascades verantwoordelijk voor de ontwikkeling en stressreacties in planten. Ondanks de brede toegang tot hoogwaardige genoomsequenties, is de set van genen met een bekende functie nog lang niet compleet. Met de komst van nieuwe bulk en single-cell omics-profileringsmethoden zijn we een nieuw tijdperk ingegaan waarin geavanceerde en integratieve functionele annotatiestrategieën worden ontwikkeld. We beschrijven een nieuwe netwerkgebaseerde geautomatiseerde functievoorspellingsmethode, en gebruiken deze om functies toe te kennen aan Arabidopsis thaliana genen. Het gebruik van chromatine-toegankelijkheidsinformatie voor een prior graafstructuur uit te lijnen bij het afleiden van gen regulatie netwerken zou het aantal vals positieven moeten verminderen. We bevestigen dit en benadrukken dat veelgebruikte, op gen expressie gebaseerde methoden er niet in slagen om regulatorische netwerken betrouwbaar te reconstrueren. In plaats daarvan bieden aanwijzingen van fysieke eiwit-DNA-interactie, versterkt door aanrijkingsstatistieken in chromatine-toegankelijkheids- of gen expressie data, een nauwkeurigere weergave van genregulatie. De regulatoire signalen die de xyleemidentiteit en celtype overgangen tot stand brengen zijn grotendeels onbekend. Door gebruik te maken van single-cell expressie data, netwerk reconstructie en complementaire regulator prioriteringsmethoden, voorspellen we nieuwe kandidaten met hoge betrouwbaarheid

Nation-building and mass education in Chile : the rationales behind the expansion of education in Chile, 1810–1920

This paper looks at the arguments that were used to further mass education in Chile. As the plausibility of the arguments depends on structural conditions, argumentative changes also shed light on changes in these conditions. We argue, more particularly, that the orientation of the debate shifted from religion vs. science to politics and to the economy, and that the ways in which education had to position itself and ensure support for its expansion thus also changed in the period of the 'long' nineteenth century. The specifics of this constellation might be distinctive of the social and educational landscape in Chile, but analyses of this constellation might also help clarifying the expansion of mass education in various other nation-states, and hence contribute to our understanding of the complexities of world society

Tell me a story! Narrative-driven XAI with Large Language Models

Existing Explainable AI (XAI) approaches, such as the widely used SHAP values or counterfactual (CF) explanations, are arguably often too technical for users to understand and act upon. To enhance comprehension of explanations of AI decisions and the overall user experience, we introduce XAIstories, which leverage Large Language Models (LLMs) to provide narratives about how AI predictions are made: SHAPstories based on SHAP and CFstories on CF explanations. We study the impact of our approach on users’ experience and understanding of AI predictions. Our results are striking: over 90% of the surveyed general audience finds the narratives generated by SHAPstories convincing, and over 78% for CFstories, in a tabular data experiment. More than 75% of the respondents in an image experiment find CFstories more or equally convincing as their own crafted stories. We also find that the generated stories help users to more accurately summarize and understand AI decisions than they do when only SHAP values are provided. The results indicate that combining LLM generated stories with current XAI methods is a promising and impactful research direction

Understanding the survival mechanisms of Campylobacter jejuni in human hosts and in the environment

Campylobacter is a bacterial pathogen that is transmitted mainly through contaminated food causing the so-called campylobacteriosis, the most frequently reported gastrointestinal disease in the European Union since 2005, with more than 127,000 human cases in 2021. Although campylobacteriosis is a self-limiting disease and the use of antibiotics is reserved for the treatment of the most severe cases and immunocompromised patients, in extreme situations, it can trigger complications such as neurological disorders like the Guillain-Barré syndrome or reactive arthritis, and myocarditis, among others. In most reported cases, Campylobacter jejuni is the predominant species, which represents a serious threat to human health, causing a negative impact on the economy of public health systems. Therefore, this Doctoral Thesis aims to study in more detail the molecular mechanisms of pathogenicity and virulence of C. jejuni to resist the harsh environmental conditions existing along the food supply chain and survive the defense mechanisms of the human host with the purpose of improving food safety. The study of the molecular bases of C. jejuni pathogenicity requires Whole-Genome Sequencing (WGS) of the isolates, as well as subsequent genome analysis of the sequenced data. This arises the need to develop a workflow ―CamPype― to automatically analyse WGS data, especially of this genus. CamPype allows the user to customize the WGS analysis to be performed, including quality control of raw reads and read quality filtering, read extension and assembly, bacterial typing, genome annotation, searching for antibiotic resistance and virulence genes, and plasmids, pangenome construction and identification of nucleotide variants. To validate CamPype, 145 Campylobacter spp. genomes, including the species C. jejuni, Campylobacter coli and Campylobacter lari, corresponding to isolates from different stages of the poultry supply chain, as well as clinical strains, from Spain were analysed. The study revealed a wide genetic diversity between and within these species, with a predominance of the lineage Clonal Complex (CC)21, which was identified at all sampling locations. Likewise, several virulence and antibiotic resistance profiles were identified, with a higher frequency of virulence genes found in the species C. jejuni that could explain its greater abundance in the environment. High rates of antibiotic resistance genes were observed, especially against β-lactams, fluoroquinolones and tetracyclines, especially in C. jejuni and C. coli, which justify the threat to global health of increasing antibiotic resistance. On the way to understanding the behaviour of Campylobacter in the environment, two isolates of C. jejuni that had infected two children from the same family at the same time were genomically compared to find the molecular traits that led the boy to suffer from perimyocarditis after the episode of campylobacteriosis. The isolates turned out to be clones of the same bacteria and only differed in 16 Single Nucleotide Polymorphisms (SNPs), which mainly affected the ON/OFF state of hypervariable genes. These differences suggest that, when infection of the human host occurs, the bacteria are able to modulate the expression of certain genes to adapt its behaviour to the environment, which can lead to the development of subsequent complications in the host depending on his/her state. The two previous strains were also phenotypically characterized, together with three different C. jejuni isolates representing different stages of the poultry supply chain, whose genomes were analysed to search for possible genetic markers responsible for the observed phenotypes. Specifically, the behaviour of the isolates was evaluated against typical stress conditions found in the poultry supply chain, such as their ability to tolerate oxygen and oxidative stress, as well as their ability to form biofilm as an adaptive strategy in the food industry, which depends on bacterial motility. The isolates combined different phenotypic behaviours, with special relevance the different swimming ability of the two isolates related to the perimyocarditis case. Furthermore, the comparative analysis of the genomes revealed differences in the pattern of genes associated with the survival strategies evaluated, although the underlying molecular mechanism of each phenotype was mainly the phase variation of hypervariable genes, which was crucial to modulate the diverse survival mechanisms adopted by the bacteria. The different swimming ability of the two isolates related to the perimyocarditis case led to an in-depth study of the motility phenotype in C. jejuni, which again revealed a great diversity in the swimming ability of the bacteria, as well as in the patterns of genes associated with this phenotype and in phasotypes ―combinations of the ON/OFF state of hypervariable genes―. This indicates that motility is a complex phenotype that combines distinct but complementary genetic mechanisms, which determine different swimming abilities. Among these mechanisms, there exists the presence of genes that code for structural proteins of the flagellum, glycosylation proteins of the flagellum that modify its composition, regulatory proteins and chemoreceptors, although the shortening of proteins as a consequence of point mutations or the expression state of those hypervariable genes, which those involved in the glycosylation of the flagellum stand out, are decisive to explain the variability of this phenotype. The previous analysis was complemented with a Genome-Wide Association Study (GWAS) that revealed new findings involved in the motility phenotype from a statistical point of view, considering both the set of the genes and mutations found among all isolates. In particular, up to four regions in the genome seemed to be involved in the greater or lesser swimming ability of the bacteria, regions that code for membrane, transmembrane, periplasmic and capsule proteins, which suggest a fundamental role for the structure and composition of the membrane and capsule in the performance of the bacteria in viscous environments. In addition to the need for correct assembly of the flagellum in a highly ordered process, the phosphate ABC and ATP-binding transporters could be key in the transference of nutrients for the generation of the proton-motive force across the membrane, necessary for the rotation of the flagellum at greater or lesser speed allowing longer or shorter swimming distances of the bacteria. In this way, these last two studies highlight the importance for understanding the motility phenotype in C. jejuni of studying both the genes directly involved in the construction of the flagellum and those genes responsible for starting up the functioning of this filamentous structure. In conclusion, this Doctoral Thesis demonstrates the potential of CamPype to genomically characterize isolates from different species and origins, generating new data useful for subsequent more specific analyses that allow further studies of the molecular bases of C. jejuni pathogenicity. The bacteria are characterized by their ability to efficiently combine diverse and complex genetic mechanisms, among which there are virulence factors involved in multiple processes, several of which are affected by phase variation and that determine different phenotypes, and diverse mechanisms of antibiotic resistance. Although of all these, the phase variation is the mechanism that gives the bacteria the essential adaptive advantage to face stress situations, overcome adverse environmental conditions and adapt to the host, which makes the behaviour of the bacteria to be almost unpredictable and enhances its prevalence in the environment

Performance analysis of the collective heating system in three multifamily buildings using in situ monitoring

To reduce carbon emissions in buildings, the share of renewable energy for heating must increase significantly. For an apartment building it can be challenging to integrate these renewable energy technologies, due to lack of space in a single apartment unit. Therefore, switching to a collective heating system facilitates the incorporation of renewable sources, but inevitably, increases the distribution losses, reducing the energy efficiency of the system. This case study analysis discusses the theoretical and actual performance of three multi-family buildings with collective hydronic heating systems with a single circulation pipe for both space heating and domestic hot water, connected to an array of solar thermal collectors. Calorimeters at various points in the system allow a detailed mapping of the heat flows in the buildings. The analysis of this monitoring data show that considerable heat losses occur throughout the storage and distribution system, resulting in a low system efficiency. Particularly in summer months, only a fifth of the generated heat is used beneficially, since there is no space heating demand but the circulation pipe continues to pump water at a high temperature to cover the limited demand for domestic hot water. These total heat losses are significantly higher than what was theoretically determined. Moreover, the contribution of the solar collectors is limited and the absorbed solar heat injected in the system does not outweigh the distribution losses. Consequently, the choice for a collective installation must be weighed with care so that it can contribute to an improved energy performance

Sauver les riches: la charité à Lille à la fin du Moyen Âge

This PhD thesis concerns the profits generated by the accomplishment of the seven works of mercy in Lille, during the last three centuries of the Middle Ages. Within the County of Flanders, Lille is a quiet astonishing town, especially compared to its Dutch-speaking neighbours. Its case has only seldom been studied. Lille was successively ruled by the counts of Flanders, the kings of France and the dukes of Burgundy. In 1237, Countess Joan of Constantinople founded for the sake of her soul, a hospital that she endowed a lot. The goal of the institution was to welcome as many pauperes Christi as possible. At the very beginning of the 16th century, the density of charitable institutions in a 25 000 inhabitants town (a generous hypothesis) was very high, with 16 hospitals, one orphanage in developement, seven parochial charities and numerous alms made by individuals. The goal of helping the pauperes Christi was at the heart of numerous memorial devices. Charitable institutions constituted an important economic issues, due to their wealth and needs in goods and workforce. A prosopographical research shows that their management allows people who could not participate to the Magistrat to obtain an honourable place into the society. Finally, this study shows that the control of charitable institutions – even if indirect – does not only represent a political issue between citizens and their rulers but reinforces their connections

Advancing time series data analytics and applied machine learning in healthcare

Tijdreeksdata bestaat uit een reeks waarnemingen, elk gekoppeld aan een specifiek tijdstip. Dit type data is wijdverspreid in verschillende sectoren, waaronder de gezondheidszorg, financiële sector en transport. De analyse van tijdreeksdata brengt echter diverse uitdagingen met zich mee. Twee van deze uitdagingen zijn enerzijds schaalbaarheid naar grotere datasets en anderzijds het kunnen omgaan met de diversiteit binnen tijdreeksdata. Deze uitdagingen beïnvloeden het inzicht, de interpretatie en de verwerking van tijdreeksdata. Dit speelt een belangrijke rol in machinaal leren, waar de interpretatie van modellen essentieel is, met name in de gezondheidszorg. Daar is het van cruciaal belang om over oplossingen te beschikken die klinisch transparant en acceptabel zijn. Dit doctoraat richt zich op het overwinnen van de bovenstaande uitdagingen in bestaande tools en technieken voor effectieve tijdreeksdata-analyse. De ontworpen open-source tools en algoritmische innovaties, waaronder Plotly-Resampler, MinMaxLTTB, tsdownsample en tsflex, bieden efficiënte en flexibele oplossingen aan voor de visualisatie en verwerking van tijdreeksdata. Deze tools en technieken kunnen gebruikt worden voor meer transparante en klinisch acceptabele toepassingen van machinaal leren in onder andere de gezondheidszorg, wat wordt aangetoond met slaapscoring. Om verder te focussen op klinische acceptatie wordt traditionele machinaal leren gebruikt om een nieuwe methode te ontwikkelen voor lenssuggestie tijdens cataractoperaties

Effects of different processing techniques on oxidation during mealworm protein fractionation and simulated gastrointestinal digestion

Effects of different processing techniques on oxidation during mealworm protein fractionation and simulated gastrointestinal digestion Alternative protein sources are increasingly in demand to replace, at least in part, meat in the human diet. Commonly, these alternative protein sources are of vegetable origin, but could also include protein from insect, such as mealworm (Tenebrio molitor). Several processing steps are required to extract and purify mealworm protein from its original matrix. Little is known how the oxidative quality of mealworm is affected by the killing and drying method, protein extraction, and subsequent gastrointestinal digestion. In this study, mealworms were subjected to two different killing methods: blast-freezing (-38°C, 4h) or blanching (100°C, 40s), and two different drying methods: oven drying (65°C, 3d) or freeze-drying (-20°C, 4d), and then ground into four different full-fat flours. These flours were then defatted with ethyl acetate (1:3) to produce four defatted flours and finally subjected to isoelectric point precipitation to produce four different protein concentrates. This way, a total of twelve samples were obtained and subjected to in vitro digestion, simulating the conditions from the mouth to the small intestine. HPLC-FLD was used to measure the levels of lipid oxidation products (hexanal, propanal, and 4-hydroxy-2-nonenal) and the glycoxidation product pentosidine. In addition, total Maillard reaction products (MRPs) were extracted using methanol and determined spectrophotometrically. The different processing and extraction steps had a clear effect on the levels of oxidation products found in the mealworm extracts and after their in vitro digestion. Freeze-drying promoted lipid oxidation in full-fat flours and increased further during in vitro digestion. In oven-dried samples, the amount of lipid oxidation products was almost absent. All defatted flours, independent of prior treatment, showed relatively very low amounts of lipid oxidation products, which were probably lost during defatting and did not increase after digestion. In the protein concentrates, the blanched samples showed an increase in lipid oxidation products, however the blast-frozen samples did not. Compared to the other treatments, relatively high levels of pentosidine and MRPs were formed in all the blast-frozen oven-dried samples, these were also present in the protein concentrate prepared by blast-freezing and freeze-drying. In vitro digestion did not increase the pentosidine concentration, but increased the amount of MRPs. Of interest, all samples with high glycoxidation concomitantly contained relatively low levels of lipid oxidation products. In summary, varying processing techniques influenced the oxidative quality of mealworm protein extracts. Also, the study revealed a potential link between elevated glyc(o)xidation and reduced lipid oxidation during both processing and digestion