DaMAT: A Data-driven Mutation Analysis Tool

in Proceedings of the 45th International Conference on Software Engineering (ICSE ’23) (in press)

We present DaMAT, a tool that implements data- driven mutation analysis. In contrast to traditional code-driven mutation analysis tools it mutates (i.e., modifies) the data ex- changed by components ... [more ▼]

We present DaMAT, a tool that implements data- driven mutation analysis. In contrast to traditional code-driven mutation analysis tools it mutates (i.e., modifies) the data ex- changed by components instead of the source of the software under test. Such an approach helps ensure that test suites appropriately exercise components interoperability — essential for safety-critical cyber-physical systems. A user-provided fault model drives the mutation process. We have successfully evalu- ated DaMAT on software controlling a microsatellite and a set of libraries used in deployed CubeSats. A demo video of DaMAT is available at https://youtu.be/s5M52xWCj84 [less ▲]

»Comic«

in Bay, Hansjörg; Hamann, Christof; Osthues, Julian (Eds.) et al Handbuch Literatur und Reise (in press)

Cultural Border Studies

in Nesselhauf, Jonas; Weber, Florian (Eds.) Handbuch Kulturwissenschaftliche Studies (in press)

Transcriptional and Chromatin Accessibility Profiling of Neural Stem Cells Differentiating into Astrocytes Reveal Dynamic Signatures Affected under Inflammatory Conditions

in Cells (2023), 12(6), 948

Astrocytes arise from multipotent neural stem cells (NSCs) and represent the most abundant cell type of the central nervous system (CNS), playing key roles in the developing and adult brain. Since the ... [more ▼]

Astrocytes arise from multipotent neural stem cells (NSCs) and represent the most abundant cell type of the central nervous system (CNS), playing key roles in the developing and adult brain. Since the differentiation of NSCs towards a gliogenic fate is a precisely timed and regulated process, its perturbation gives rise to dysfunctional astrocytic phenotypes. Inflammation, which often underlies neurological disorders, including neurodevelopmental disorders and brain tumors, disrupts the accurate developmental process of NSCs. However, the specific consequences of an inflammatory environment on the epigenetic and transcriptional programs underlying NSCs’ differentiation into astrocytes is unexplored. Here, we address this gap by profiling in mice glial precursors from neural tissue derived from early embryonic stages along their astrocytic differentiation trajectory in the presence or absence of tumor necrosis factor (TNF), a master pro-inflammatory cytokine. By using a combination of RNA- and ATAC-sequencing approaches, together with footprint and integrated gene regulatory network analyses, we here identify key differences during the differentiation of NSCs into astrocytes under physiological and inflammatory settings. In agreement with its role to turn cells resistant to inflammatory challenges, we detect Nrf2 as a master transcription factor supporting the astrocytic differentiation under TNF exposure. Further, under these conditions, we unravel additional transcriptional regulatory hubs, including Stat3, Smad3, Cebpb, and Nfkb2, highlighting the interplay among pathways underlying physiological astrocytic developmental processes and those involved in inflammatory responses, resulting in discrete astrocytic phenotypes. Overall, our study reports key transcriptional and epigenetic changes leading to the identification of molecular regulators of astrocytic differentiation. Furthermore, our analyses provide a valuable resource for understanding inflammation-induced astrocytic phenotypes that might contribute to the development and progression of CNS disorders with an inflammatory component. [less ▲]

Un débat parlementaire sur une politique "inhumaine" (Les Italiens dans le Luxembourg des migrations, 6e partie)

Article for general public (2023)

Measuring biological age using a functionally interpretable multi-tissue RNA clock

in Aging Cell (2023)

Continuer à faire réseau : le regard d’une chercheuse sur le projet Respadon (conclusion de la journée).

Scientific Conference (2023, March 13)

L’équipe de ResPaDon organise une journée d’échange autour des résultats et des perspectives de ce projet débuté en mars 2021. Des conditions d’accès aux collectes collaboratives, des enjeux juridiques à ... [more ▼]

L’équipe de ResPaDon organise une journée d’échange autour des résultats et des perspectives de ce projet débuté en mars 2021. Des conditions d’accès aux collectes collaboratives, des enjeux juridiques à la coopération entre acteurs nationaux et établissements de proximité, le Réseau de Partenaires pour l’exploration et l’analyse de données numériques (ResPaDon) propose de partager les résultats de sa démarche pour développer les usages scientifiques de la collection des archives du dépôt légal du web. [less ▲]

Observing unseen flowlines and their contribution to near stream endmembers in forested headwater catchments.

Doctoral thesis (2023)

The general scope of the PhD research project falls within the framework of developing integrated catchment hydro-biogeochemical theories in the context of the Critical Zone (CZ). Significant advances in ... [more ▼]

The general scope of the PhD research project falls within the framework of developing integrated catchment hydro-biogeochemical theories in the context of the Critical Zone (CZ). Significant advances in the understanding of water transit time theory, subsurface structure controls, and the quantification of catchment scale weathering rates have resulted in the convergence of classical biogeochemical and hydrological theories. This will potentially pave the way for a more mechanistic understanding of CZ because many challenges still exist. Perhaps the most difficult of all is a unifying hydro-biogeochemical theory that can compare catchments across gradients of climate, geology, and vegetation. Understanding the processes driving the evolution of chemical tracers as they move through space and time is of cardinal importance to validating mixing hypotheses and assisting in determining the residence time of water in CZ. The specific aim of the study is to investigate what physical and biogeochemical processes are driving variations in observable endmembers in stream discharge as a function of the hydrological state at headwater catchment scale. This requires looking beyond what can be observed in the stream and what is called ”unseen flowlines” in this thesis. The Weierbach Experimental Catchment (WEC) in Luxembourg provides a unique opportunity to study these processes, with an extensive biweekly groundwater chemistry dataset spanning over ten years. Additionally, WEC has been the subject of numerous published works in the domain of CZ science, adding to an already detailed hydrological and geochemical understanding of the system. Multivariate analysis techniques were used to identify the unseen flowlines in the catchment. Together with the excising hydrological perception model and a geochemical modelling approach, these flowlines were rigorously investigated to understand what processes drive their respective manifestations in the system. The existing perceptual model for WEC was updated by the new findings and tested on 27 flood events to assess if it could adequately explain the c − Q behaviour observed during these periods. The novelty of the study lies in the fact that it uses both data-driven modelling approaches and geochemical processbased modelling to look beyond what can be observed in the near-stream environment of headwaters. [less ▲]

Senescence as a Converging Mechanism in Parkinson's Disease

Doctoral thesis (2023)

Neurodegenerative diseases are one of the leading causes of disability and mortality, affecting millions of people worldwide. Parkinson’s disease (PD) is the second most common neurodegenerative disease ... [more ▼]

Neurodegenerative diseases are one of the leading causes of disability and mortality, affecting millions of people worldwide. Parkinson’s disease (PD) is the second most common neurodegenerative disease globally, and while it was first described over 200 years ago, curative treatments remain elusive. One of the main challenges in developing effective therapeutic strategies for PD is the complex molecular pathophysiology of the disease has not been well recapitulated in classically used animal models systems, and studies using post-mortem tissue from patients only represents the end point of disease. Human derived brain organoid models have revolutionized the field of neurological disease modeling, as they are able to recapitulate key cellular and physiological features reminiscent of the human brain. This thesis describes the use of human midbrain organoids (hMO) to model and gain a deeper understanding of genetic forms of PD. In the first manuscript, patient-specific hMO harboring a triplication in the SNCA gene (3xSNCA hMO) were able to recapitulate the key neuropathological hallmarks of PD. We observed the progressive loss and dysfunction of midbrain dopaminergic neurons in 3xSNCA hMO, and the accumulation of pathological α-synuclein including elevated levels of pS129 α-synuclein and the presence of α-synuclein aggregates. We also identified a phenotype indicative of senescence in the 3xSNCA hMO, which represents a mechanism that has recently gained more attention as a driving factor in PD pathogenesis and progression. The second manuscript of this thesis investigated the pathogenic role of LRRK2-G2019S in astrocytes using a combination of post-mortem brain tissue, induced pluripotent stem cell derived astrocytes and hMO. The iPSC derived astrocytes and organoids recapitulated the phenotypes seen in the post-mortem tissue, emphasizing the validity of these models in reflecting the in vivo situation. Interestingly, single-cell RNA sequencing of the hMO revealed that astrocytes from the LRRK2-G2019S organoids showed a senescent-like phenotype. Thus, this thesis highlights the relevance of senescence as a converging mechanism in PD. Finally, this thesis explores the future development of organoid models as they are combined with technologies such as microfluidic devices as in Manuscript III to improve their complexity and reproducibility. Ultimately, this will lead to the development of more representative models that can better recapitulate and model PD as well as other neurodegenerative disorders. [less ▲]

« La cour d’assises semble être devenue une succursale de l’Académie française ». Figurations de l’éloquence judiciaire dans l’œuvre de Courier et de Béranger

in Romantisme (2023), 199(1), 16-25

In 1821 Paul-Louis Courier, accused of outrages to public morality because of his Simple discours (1821) and Pierre-Jean de Béranger, prosecuted for having outraged, with his Chansons (1821), public and ... [more ▼]

In 1821 Paul-Louis Courier, accused of outrages to public morality because of his Simple discours (1821) and Pierre-Jean de Béranger, prosecuted for having outraged, with his Chansons (1821), public and religious morality and social mores, and insulted the king, appeared before the Assizes court of the Seine. These two famous trials inspired both Courier and Béranger to write respectively the Procès de Paul-Louis Courier (The Trial of Paul-Louis Courier) and the Procès fait aux chansons de P.-J. de Béranger (The Trial against the Songs of P.-J. de Béranger). This paper aims to study through the lens of these texts the manner in which Courier and Béranger understand and appropriate, within texts that need to be considered as both aesthetic declarations and political professions of faith, the judicial eloquence manifested during their respective trials. [less ▲]