Luxembourg National Research Fund

Abstract

DNA (=deoxyribonucleic acid) can adopt different conformations according to the succession of the various nucleotides that make it up and the number of strands involved. In addition to the widespread and now well-known duplex forms, specific DNA sequences, which are very rich in guanines (one of the 5 bases found in DNA/RNA), can adopt a more particular conformation, which corresponds to G-quadruplexes (G4s). These particular DNA (or RNA) structures comprise a stack of at least two guanine plates, also called quartets, formed by the association of four guanines interacting with each other by H bonds.

In the last decades, one approach that has been more and more explored in anti-cancer drug design is by targeting those G-quadruplexes. These G4 motifs have indeed received a great deal of attention as promising targets in the development of therapeutic agents because of their location at the end of chromosomes, in the telomeres. In fact, telomeres are shortened after each cell division until they reach a critical length at which the cell is no longer able to divide. A cell death mechanism, called apoptosis, is then triggered, eliminating cells that have accumulated too many mutations during division cycles. However, in the majority of cancer cells, the telomere length is maintained following overexpression of telomerase, an enzyme which allows telomeric DNA sequences to be added at the end of telomeres. Cancer cells can therefore be regarded as “”immortal”” since they can divide ad infinitum. In addition to telomeric DNA, G-quadruplex structures have also been located in the transcriptional regulatory regions of many oncogenes, as well as in other cancer-related genes. The stabilisation of G-quadruplex structures is therefore a major challenge in order to study their precise biological roles, such as, for example, the inhibition of telomerase activity once the G4s are stabilised.

As the understanding of the biological roles of the different G4 systems is still fragmentary, it is, therefore, necessary to develop compounds capable of selectively stabilising the various structures to study them. Among the various examined compounds, polyazaaromatic ruthenium(II) complexes showed great promise. The advantage of these complexes lies in particular in their ability to modulate their optical and electronic properties by tuning the nature of the ligands. In particular, it is possible to induce, depending on the ancillary ligands selected, either light-up probe properties or properties as a photoreactive agent capable of binding covalently to G4. The extent and geometry of the planar ligand chelated at the metal centre also allow promoting a selective interaction towards G4s.

The development of polyazaaromatic ruthenium(II) complexes as molecular tools for the study and covalent or non-covalent stabilisation of G-quadruplexes will be at the core of this project. More precisely, our research aims at the design of complexes bearing two types of extended (symmetrical or elbow) ligands and two types of ancillary ligands. The different extended ligands will allow deriving a structure – affinity/selectivity relationship (SAR) for the resulting complexes, the ancillary ligands will allow the tuning of the photoreactivity towards the G4s. The project will thus be divided into three axes: the synthesis of the different compounds, the determination of their optical and electrochemical properties and their study in presence of several G4 structures.

There is no cure for glioblastoma (GBM), the most lethal primary brain tumor. Cancer cells must activate mechanisms to maintaining telomeres, the physical ends of our chromosomes, in order to acquire limitless replicative potential. Although targeting DNA repair and telomere maintenance mechanisms have emerged as important therapeutic strategies for many cancers, identifying suitable targets for such strategies in GBM remains a considerable challenge.

Telomeres need special protection from oxidative DNA damage – an inevitable consequence of cellular metabolism. Involved in the removal of oxidized guanines in telomeric DNA is the DNA repair protein NEIL3. We have shown that NEIL3 is required for telomere protection and chemoresistance in GBM cells, suggesting that it represents a relevant target to eradicate GBM.

This proposal aims to understand the molecular mechanisms whereby NEIL3 regulates telomere dynamics in adult and pediatric GBM. It also aims to evaluate the importance of NEIL3 in epigenetic mechanisms controlling gene expression, and test its potential as a therapeutic target in GBM. Our experiments may pave the way for novel DNA repair-based strategies against GBM. As telomeres play a central role in aging, our research may also have implications for aging-associated disorders.

The highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), is transmitted by inhalation of respiratory droplets carrying infectious virus. COVID-19 represents a mild to moderate respiratory illness in most people, but can develop into a more serious illness in older people and those with pre-existing medical conditions. After inhalation, respiratory viruses have to overcome the body´s first-line defence against inhaled particles to further advance into the lungs. This primary defence, also known as mucociliary clearance, is made out of two main actors. First, a layer of mucus paving the walls of the trachea and nose filters the inhaled air, capturing inhaled particles, before it reaches the lungs. Secondly, thin, hair-like structures, also known as motile cilia, emerging from specialized cells in the nasal cavity and trachea are continuously evacuating the mucus from the airways by rhythmic beating. If ciliary function is inhibited, the first-line defence of the body is compromised and viruses and other germs can easily conquer the airways and progress into the lungs. Even if damage to these motile cilia is a common feature of several respiratory viruses, underlying mechanisms responsible for ciliary damage are still poorly understood and investigations of how SARS-CoV-2 damages this defence mechanism have not been performed so far. Secondly, loss of smell (otherwise known as anosmia) is a commonly observed symptom of SARS-CoV-2 infection. Despite the frequency of this feature, the underlying reason for the loss or alteration of smell remains enigmatic. The suspected cause is a functional disruption of the tissue inhabiting the cells responsible for odour detection in the nose (also known as olfactory epithelium). Furthermore, the anatomical proximity between the olfactory epithelium in the nose and the brain represents a potential shortcut for the virus to enter the brain, potentially leading to more severe course of disease with neurologic symptoms. So far, it is unknown if SARS-CoV-2 uses this shortcut to the brain, which underlines the urgent need for studies in this area.

The first part of the proposed project aims at investigating the mechanism of damage to the mucociliary clearance and specifically motile cilia in the trachea and the nose in order to understand how SARS-CoV-2 proceeds into the lungs. The second part focuses on consequences of SARS-CoV-2-infection in the nose, specifically the olfactory epithelium, and in the brain, specifically the olfactory bulb, where odour signals are received from the nose.

To accomplish the tasks of this project, samples from the nose, trachea, lungs and brain are derived from experiments in three animal species. Investigated animals are susceptible to SARS-CoV-2 infection and are used as animal models to simulate human COVID-19. These include Syrian golden hamsters, ferrets and transgenic mice, the latter expressing the human angiotensin-converting-enzyme-2 (hACE2) protein, famous as one of the main entry receptors for SARS-CoV-2. Applied techniques include (i) light microscopic analysis using various staining methods to characterize tissue damage and cells containing viral particles, (ii) scanning electron microscopy to evaluate three-dimensional changes to the air conducting surface motile cilia as well as (iii) transmission electron microscopy to detect details of intracellular changes. The results will offer a detailed, chronologic description of the consequences of SARS-CoV-2 infection in the upper respiratory tract.

The research project is of high relevance for the research community and will pave the way for further investigations on the origins of SARS-CoV-2-related respiratory and neurologic illness in humans.”

Tropical coral reefs are valuable ecosystems upon which millions of people rely for subsistence. Unfortunately, they are currently facing increasing threats, mostly through global warming. Because of this ecological emergency, restoration techniques will become crucial for re-establishing the biodiversity of damaged reefs and increasing the resilience of these vulnerable ecosystems.
Ecological engineering could offer solutions to this problem, for instance through the designing of adapted artificial reefs. Coral juveniles, called recruits, need an appropriate substrate to settle onto. The factors influencing the recruitment process and survival are still poorly understood. Settlement tiles of different materials and complexities will be deployed on the forereef of Moorea, in French Polynesia. The presented PhD project aims to study the influences of these materials, their textures and their benthic colonisation on coral recruitment. These influences will also be tested on the long-term survival and development of coral juveniles, by analysing the tiles after 6, 12 and 18 months. If innovative artificial materials can significantly increase the coral recruitment and survival rates of a site, they could be used for large scale reef restoration actions.

Another promising technique is the creation of coral nurseries. In these nurseries, the team of Dr Hédouin are growing ‘super corals’, which are genotypes capable of resisting to extreme environmental conditions. They were selected because of their survival during multiple mass bleaching events. The correlation between their resistance and environmental parameters, coral physiology and microbiome diversity will be analysed. Through a series of transplantations of colonies of the same genotype, we will determine if the resistance is due to a genetic adaptation or simply to a reversible adaptation. The transmission of the resistance to the following generation will also be tested after spawning events. Sexual crossing of resistant colonies could be a way to produce new genotypes fit to sustain the future climate conditions. Through the proposed experiments, the properties of ‘super corals’ will be analysed and their potential as a restoration tool will be evaluated.

This project will be the first of its kind in French Polynesia. Ultimately, these innovative and poorly studied techniques could be applied to increase the resilience of tomorrow’s coral reefs. The development of potential ‘super substrates’ and ‘super corals’ will undoubtedly be a promising method to assist corals in the Anthropocene and preserve these valuable ecosystems.

Each cell in the body can be compared to a small factory. Just as a factory has many production lines with a variety of different machines, a cell contains distinct compartments dedicated to particular production steps. The endoplasmic reticulum (ER) is the cell’s largest compartment and it acts as a machine that produces proteins. These proteins are assembled from building blocks called amino acids, folded into their three-dimensional finished structure, and shipped to their final destinations inside or outside the cell.

However, both man-made and cellular machines can run into problems or even break down entirely. In that case, it is crucial to identify the problem and fix it as fast as possible in order to avoid turning out faulty products. The proper function of the endoplasmic reticulum can be disrupted by external factors, such as heat or pathogens, causing so-called “ER stress”. This can lead to the accumulation of incorrectly folded proteins inside the ER, thus clogging the compartment. Consequently, the ER is unable to fulfil its job in protein production, which threatens cell survival. Luckily, cells have developed elaborate strategies to solve such problems. They have surveillance systems that monitor the state of the ER and mechanisms that unclog the ER if necessary, so that it can resume its normal function. These cellular stress responses act like a repair service for the ER and are critical for the survival of the cell. ER dysfunction has been linked to several diseases such as diabetes and cancer.
For this reason, in my PhD project, I focus on a recently discovered cellular stress response at the ER. In our lab, we observed that during ER stress, the membrane surrounding the ER appears to be damaged in some places. This is equivalent to a machine in the factory production line having a crack or leak. We also noticed that certain proteins of the so-called ESCRT machinery are recruited and directed to these damaged regions. We think that this machinery might act as a repair service for the ER. Now I want to find out how this repair service works. My research will contribute to a more complete understanding of what happens in a cell during ER stress. Once we gain a better understanding of how cellular stress responses work, we can determine what goes wrong during disease and we can develop new therapies that assist cells in keeping their internal compartments in good working order.

When most people think of neurological disorders, a small number of diseases that affect millions of people such as epilepsy, Alzheimer’s disease, Parkinson’s disease, and stroke come to mind. While scientists and funding agencies focus the majority of their efforts on these devastating diseases, research programs devoted to finding the fundamentals and treatments for numerous rare diseases are largely lacking. A disease is defined as rare in Europe when it affects less than 1 in 2000 people. Over 7,000 different rare diseases have been identified to date. Therefore, taken together, rare diseases currently affect 3.5% to 5.9% of the worldwide population, an estimated 30 million people in Europe, and 300 million worldwide. Due to the low prevalence of each disease, medical expertise is rare, knowledge is scarce, care offerings inadequate and research limited. Thus, despite their large overall number, rare disease patients are the orphans of health systems. The fact that there are often no existing effective treatments and even less cures, adds to the high level of pain and suffering endured by patients and their families.

Congenital disorders of glycosylation (CDGs) comprise a rapidly expanding group of rare diseases caused by genetic defects that compromise the preservation of the sugar structures that are attached to many of our proteins or lipids and that play important roles in the biological functions of these biomolecules. Such defects can affect multiple organ systems, with nearly always an important neurological component. CDGs can be associated with a broad variety of symptoms and can vary in severity from mild cases to severe, disabling or life-threatening forms. Most CDGs are inherited as autosomal recessive conditions, meaning that sick children are born from healthy parents. CDG symptoms are usually apparent from infancy. The N-linked protein glycosylation defect PMM2-CDG, was the first CDG to be reported by Jaeken in 1980. Since then, more than 130 types of CDGs have been identified, and that number continues to grow. Efforts are now guided towards (i) the identification of gene defects causing novel CDGs, (ii) the understanding of how the genetic defects lead to disease symptoms in known CDGs, (iii) the development of more efficient practices to shorten the diagnostic path for patients, and (iv) the development of specific therapeutic approaches for CDGs, including the rarest cases.

In that context, we will define the molecular basis of two human CDGs caused by genetic defects in substructures of an enzyme called GDP-mannose pyrophosphorylase (GMPP). GMPP is responsible for the cellular synthesis of GDP-mannose, the most common compound used in transfer of the sugar mannose to proteins and lipids in humans. The enzyme consists of two substructures (or subunits), called GMPPA and GMPPB. Strikingly, when GMPPA is mutated, patients suffer from a completely different pathology compared to patients with mutations in the GMPPB subunit. In this project, experiments will be designed to establish for the first time the 3-dimensional structure of the GMPP enzyme and to analyze the metabolic consequences of a deficiency of this enzyme in human cell models. This work will form a strong basis for developing improved diagnostic and therapeutic strategies for affected subjects and thereby opens perspectives for decreased suffering of patients and their families.

Alzheimer’s disease (AD), Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are the most frequent age-related neurodegenerative diseases (NDDs) and causes of dementia. The medical management of these diseases is, at this time, based on only symptomatic treatments with often important side effects. The constant increase in the incidence of NDDs constitutes a severe societal and economical challenge due to the ageing population. AD, PD and DLB are multifactorial diseases whose etiology is still poorly understood. However, these disorders share multiple cognitive symptoms such as progressive memory decline. The cellular and molecular causes for the loss of memory in NDDs still need to be characterized. Interestingly, the brain circuits of the memory are all associated with a small brain region localized in the brainstem, called the Locus Coeruleus (LC), which is strongly deteriorated in all NDDs. The LC is secreting the noradrenaline (NA), a neurotransmitter that is a strong modulator of brain cells responses. The degeneration of the LC causes a NA depletion in regions such as the hippocampus (HP), which are key to the memory process, and provokes imbalance in the NA modulatory system. The hypothesis of our work is that the LC deterioration exacerbates the memory decline across AD, PD and DLB. In this PhD project, we will conduct translational and transversal research on human cells in culture and on human post-mortem samples. With the cells in culture, we will investigate the modulatory role of NA on neurons, astrocytes and microglia in healthy and disease conditions, at cellular and molecular levels. With our collection of autopsy samples, we will characterize the neuropathological environment and the signatures of brain cells in the LC and the HP of AD, DLB and PD patient samples. To this purpose, we will use cutting edge single-cell and microscopy techniques to resolve with high precision the alterations of the NA-dependent system. This work will be supported by national and international collaborations, with the LCSB and DLSM of the University of Luxembourg, and with McGill University (Montreal, Canada) and Pitié-Salpêtrière Centre de la mémoire (Paris, France). By characterizing the modulatory role of NA across NDDs and its significance for memory decline, this project aims to improve the classification of pathological features and open new avenues for diagnostic and therapeutic approaches.

Foldable surfaces in architecture and other technical applications use connecting elements such as joints that commonly need intense maintenance and risk failure. In contrast, various structures that do not require hinges for folding can be found in the plant kingdom. Flower opening and closing, and leaf unfolding are promising biological mechanisms in this regard, but so far, only isolated plant structures have been examined for transfer into technology. Moreover, although necessary for understanding plant development and movement, the relationships between structure and function of such plant organs as well as their behaviour under mechanical loading are still poorly understood.

Thus, this project aims to analyse and compare the structures and functions, motion and unfolding patterns of various plant leaves. Investigations will concentrate on shield-shaped (peltate) leaves as these can be found in diverse habitats in which different leaf unfolding mechanisms might have developed in evolution. Detailed analysis and understanding of form structure function relationship is important to generalise mechanisms and detect similar movement and folding patterns across species. On this basis, abstraction of biological concepts is possible. Joint-free and failsafe foldable structures for usage in technical applications in aerospace, architecture and constructional engineering could be developed.

Hypoxia or the decrease in the oxygen level within tumors is a well-established factor contributing to tumor resistance to various therapies including chemotherapy and radiotherapy. We and others have reported that hypoxia can also make tumors resistant to the emerging and revolutionary cancer immunotherapy by constituting an obstacle preventing the infiltration of immune cells into the tumors, which is a prerequisite parameter to cancer response to immunotherapy. We have generated comprehensive preliminary data in mice showing that inhibiting HIF-1, the protein responsible for the establishment of hypoxia, in melanoma cells resulted in a significant inhibition of tumor volume and weight, associated with a substantial gain in survival. We also reported that blocking hypoxia induced a significant increase in the infiltration of immune cells into melanoma. The aim of this project is to understand how immune cells succeed to infiltrate melanoma following hypoxia inhibition. Such understanding is essential to propose an innovative cancer treatment based on combining drugs inhibiting hypoxia with current cancer therapies. Another aspect of the project is to evaluate the efficacy of an innovative therapeutic approach based on combining immunotherapy with drugs inhibiting hypoxia. The net outcome of the project is to establish the basis of new generation of cancer immunotherapy for the treatment of patients who are not responding to current cancer therapies.

In the next 30 years, the world’s population is expected to reach 9.7 billion people. This population growth will inevitably be accompanied by rapid urbanization and an ever-increasing demand for high-rise buildings. Consequently, reducing the consumption of natural resources and related carbon dioxide emissions for the construction market is a priority. Steel-concrete composite construction solutions are widely used in high-rise and long-span structures due to their important load-bearing capacity. In addition, those structural components can meet the requirements for sustainability.

The recent development of high-performance materials as high-strength steel and high-performance concrete could further improve composite construction. Indeed, these materials lead to slender elements and related increase of the net floor area as well as a reduction of the grey energy through resource-efficiency structures.

The use of high-strength materials in composite columns is impaired by a lack of fundamental knowledge and normative basis. LinCoCo project aims to study the behavior of the steel-concrete interface in the load introduction zone of the composite column where large forces are transferred from the floor to the column. Generally, this connection between the two materials is realized using a shear connector allowing a stronger connection than the natural chemical bond between steel and concrete. However, the composite connectors commonly used today are only of limited suitability, as their limited bearing capacity is often associated with appreciable deformations. Beyond that, there is only a little space available in the load introduction zone to arranging conventional shear connectors.

The LinCoCo project will collect scientific evidence to evaluate the innovative types of shear connectors and provide the basis for them to be applied in engineering structures. The project will offer a basis for the future extension of European Design Codes for the application of composite columns based on high-performance materials.

Additive manufacturing, commonly known as 3D printing, has revolutionised manufacturing in nearly every industrial sector it touched. Up until now, the construction industry did however not see a widespread adoption of this new technology, mainly due to missing information on the material characteristics of additively manufactured structures. The project we propose wants to overcome this issue for one particular 3D printing technique: Wire and Arc Additive Manufacturing (WAAM) for stainless-steel. WAAM uses an industrial robot combined with a welder to create metallic objects of nearly any imaginable shape and size. Analysing these objects, we want to derive and verify a numerical model of the material behaviour which can then be used by engineers and designers to run accurate computer simulations of their desired structure. This will enable a relatively easy and reliable way to verify the safety of their designs and open the path for WAAM to find a widespread adoption in the construction industry.

There is an increasing awareness that volatile organic compounds (VOCs) in the air webreathe, such as solvents or additives released from furniture or household products that were manufactured following poor standards, can have negative health effects.

This has generated a strong interest among the public to be able to detect and monitor VOCs in their homes and several products for home use are now on the market. Unfortunately, these electronics-based products often have difficulties distinguishing between different VOCs, and therefore they often have only one generic VOC signal that gives equal response to the aromas naturally released during cooking as to dangerous compounds. A better strategy for obtaining high selectivity may be to rely on the specific chemical interactions between a targeted VOC and a specific material that responds in a non-electronic manner.

The host group of COMMONSENSE has pioneered such an approach which does not only hold promise for offering high-selectivity VOC sensor for consumers, but it also enables these sensors to be wearable in clothing or incorporated in furniture textiles inthe home, as the sensor takes the form of a textile mat that changes its appearance incase of exposure to the targeted VOC. Since the sensor is non-electronic and requires no additional components, it is fully autonomous, requiring neither batteries, power supplies or internet connection.

At the heart of this sensor concept is the extraordinary responsive nature of liquid crystals (LCs), best known from their usage in displays (LCDs) in TVs, computers and phones. LCs combine well-defined structural arrangements over large scale with an easy-flowing liquid state, and this allows them to generate structural color (similar to the strong colors in peacock feathers or butterfly wings) in a way that changes sensitively to the environment. This means that they can change from blue to red, or from colorless to colored, if they are exposed to certain VOCs. In COMMONSENSE we will incorporate such LCs in the core of polymer fibers making up a non-woven textile mat (also known as fleece), giving the LC a convenient containment with a textile formfactor. The liquid state of the LC also means that it is fully flexible, ideal for wearable sensors.

Based on recent results that I obtained during my master thesis in the host group, our aim with COMMONSENSE is to produce such LC-functionalized textile mat sensors that are highly specific to certain VOCs and that respond with high sensitivity, well below the European safety thresholds, as well as quickly (within 10 seconds). Considering thematerials involved we also believe the sensors can be made at low cost and a low environmental footprint.

The process for making the sensors is called coaxial electrospinning, and it leads to some very interesting situations from a physics point of view, such as the need to stabilize a non-spherical interface between two liquids, the behavior of very large molecules (polymers) in the presence of different solvents, and what happens to the polymers when a solvent is evaporated, as well as the ability of the LC to amplify an event taking place at the scale of individual molecules to structures large enough to produce colors that we can see with our eyes. Therefore, I expect to learn much new physics as well as chemistry myself while advancing the scientific community’s understanding of these fascinating issues through my research in COMMONSENSE. And because there is such a strong concrete usefulness of the materials that I will produce, I hope to engage in discussions with the public, at events, in schools and on-line, to explain how science can solve important problems in our lives and in our socitieies.

Current Artificial Intelligence and Machine Learning research in chemistry and materials is mostly concerned with the exploration of chemical compound space. Chemistry, being the science of transformations, needs to extend the applicability of machine learning methods to modeling chemical reactivity. Thus, the proposed project aims at developing a hierarchy of methods that are capable of predicting transformations between molecules. This would be a major step forward towards applying machine learning methods in industry-relevant and pharmaceutical production processes. In particular, the developed methods would be applied to study the sequence of events leading to biomolecular synthesis (“origin of life”) on Earth.

In nature, the shell of a bug (scarabaeus) or the wings from a butterfly show rich and strong coloration with colors that strongly depend on the angle of view. This phenomenon is known as opalescence. The structural colors are due to periodic, ordered arrangements of defined nanostructures. For years, scientists try to understand and reproduce these natural arrangements to produce, for example, new functional surface coatings interesting as paints or as sensor. 2 dimensionial (2D) ordered structures can be prepared with small particles in the size range of billionths of a meter (nanometer), typically referred to as colloids. Colloidal particles are small enough so that they do not experience the gravitational force but undergo random motion due to collisions with each other and solvent molecules in dispersion.

In this project, small and large colloids will be mixed to form a binary dispersion. Specific colloids with a core-shell structure with hard cores and a soft, deformable shell will be used as multifunctional building blocks. The binary dispersion will then be injected to air/water interfaces in order to form monolayers of the colloids trapped at the interface. The ultimate goal of the project is the preparation of new 2D structures with homogenously distributed but precisely arranged small and large colloids. To achieve this, it will be crucial to suppress the separation of both particle species into domains of only large and domains of only small particles. To avoid this separation, particles with a tailored surface charge will be synthesized.

To investigate the microstructure of the arranged colloids as well as the distribution of the particles within the monolayers, the monolayers will be transferred from the air/water interface to a solid substrate. The structures will then be analyzed by different microscopy techniques in order to visualize the arrangement of the particles. Furthermore, the 2D structures will be analyzed for the first time directly at the air/water interface using optical spectroscopy to detect the properties at the interface.

The aim of the project is to have a protocol which is fast, simple and reproducible meaning that every researcher can repeat the process as described to produce the same structures. Moreover, the structures that will be developed in this project will be interesting for future applications in nanotechnology, for example, as sensors, lasers and light management structures in optical devices. The knowledge generated will be interesting for researchers in the field of colloids but also in a much broader context for chemists, physicists and material scientists.

Magnetic nanoparticles play a big role in a number of daily-life applications, e.g., as constituents of temperature-sensitive ferrofluids (which may be used as sealings), for usage in magnetic hyperthermia (where they are used to kill cancerous cells), or as contrast-enhancing agents in magnetic resonance imaging. In many of these applications the internal magnetization or spin structure of the nanoparticles is assumed to be homogeneous, i.e., it is assumed that the spins point everywhere into the same direction. However, there are more and more studies in the literature which provide evidence that this assumption is violated and that the spin structure may be highly inhomogeneous, i.e., the spin direction varies with the position inside the particle. In this project we will study how a beam of neutrons, which can be imagined as tiny magnetic compass needles, is deflected (scattered) by the spins of a nanoparticle. From such a scattering process one can obtain important information on the structural and magnetic parameters of a nanoparticle such as its size, shape, shell thickness (if present), or in particular on its spin structure. This will allow us to better understand the importance of an inhomogeneous spin structure and to assess its relevance for the above-mentioned applications.

Chemical systems are the building blocks of extremely complex and diverse phenomena that constitute the core of every living organism. These include feeding, sensing, communicating, computing, replicating, among many other activities. The key to this complexity is that these chemical systems are open and continuously driven far-from-equilibrium by the energy rich nutrients ingested by the cells. In that regard, in recent years, synthetic chemistry made spectacular progress by realizing that open reactors could produce behaviors much richer than those of closed ones. Theories describing how an external energy supply can produce such levels of complexity have been proposed, in particular by the group that I will join during my PhD. However, these theories suffer from practical limitations which prevent their effective use. The main goal of my PhD project will be to overcome these limitations and develop a thermodynamic theory for open chemical systems that will allow me to better understand how living systems can be so efficient at performing complex tasks at the chemical level despite the high level of thermal noise present at these scales.

Marian Sovereignty and Jesuit Historiography, these two poles constitute the pillars on which the historical argument of the proposed project shall rest. Centring our consideration around one of Europe’s most contested space of early modernity, the Spanish Low Countries and the duchy of Luxembourg respectively, in which concepts of sovereignty and rule were challenged, this project will argue that, from the seventeenth century onward, a vocabulary of sovereignty had been constructed and a vision of the Luxembourgish space diffused around the figure of the Virgin Mary. By focusing on the Jesuits and their activity in a space that constituted an intersection sphere of Bourbon and Habsburg spheres of influence, the project will look at how Jesuit historiography reimagined the duchy as Marian space.

The last five years have been some of the most challenging in EU’s history. Faced by a string of crises – from the migrant crisis and Brexit, through the challenges to the transatlantic alliance posed by the Trump administration, to the Covid-19 pandemic – the EU has also seen its foundations shaken from within by the rise of right-wing populism and the democratic backsliding of some of its member states. The spread of belief in a strict social order and an idea that the society is divided in two camps – ‘the pure people’ versus ‘the corrupt elite’ and other threats to the EU’s strength and cohesion have been mirrored by the events taking place in the Union’s immediate neighborhood – especially in the countries of Southeast Europe (SEE) still hoping for EU accession. These countries have faced serious threats to their democracies, constitutional systems, strategic orientation toward EU integrations, and even statehood. The rise of right-wing populism in SEE has been intensified by the state of de facto collapse of the process of Europeanization and the decreased interest of the EU in the region, as well as the entry of outside players like Russia and China into regional politics. The effects of these developments could be catastrophic, as the region continues to be ruled by unstable and fragile regimes where politicians use social polarization to maintain power. What is particularly troubling, this social polarization is kept salient through the use of some of the same issues that led to the violent collapse of the Yugoslav federation three decades ago. The constitutional structure and integrity of Bosnia and Herzegovina are contested, as are the independence and integrity of Kosovo. Right-wing populist and nationalist parties are in power in Serbia and in Montenegro, dividing the public over the previously resolved question of the union between the two states. The status of the Albanian minority in North Macedonia is also challenged, as is the political stability of the whole country. To all of this one must add the devastating economic crisis sparked by the Covid-19 pandemic and the scene is set for a political maelstrom that could destroy prospects for the region’s integration into the EU for generations to come. This state of affairs in SEE, however, did not come about suddenly. It is the direct product of the policies implemented by the different EU-level political actors over the past three decades, as well as of the rational calculations by the regional politicians on how to solidify their hold on power. This is why the central question of the proposed project is: How and why has the EU (un)intentionally contributed to the collapse of Europeanization and to the democratic backsliding in Southeast Europe? The EU itself has been divided on the Europeanization, democratization, and ultimately integration of Southeast Europe, its policy responses to the rise of right-wing populism and authoritarianism among its member states, and on its responses to the policy challenges from other powers like the US, Russia, and China. However, its divisions in these three crucial policy fields rarely feature in the scholarly accounts of the failures and successes of its approach in Southeast Europe. This study will go against that trend. It will examine the political, institutional and geopolitical (f)actors which influenced the EU process of decision making and adoption of strategies for SEE that (in)directly contributed to democratic backsliding and the rise of right-wing populism in the region. It will lift the veil of policymaking and political negotiations within the EU and between the EU and SEE countries, and expose how and why EU policies toward SEE are failing to promote democracy, but are instead encouraging authoritarianism. Lessons learned and recommendations made will be portable across regions and will serve the EU in the process of future European Neighborhood Policy evaluation and making.

After the end of World War II, European science and scientific infrastructure lay devastated. In an effort to rebuild this to its former glory, European countries decided to collaborate on some of the first international scientific research projects. An example is the Centre Européen de la Recherche Nucléaire (CERN), established in 1954, which in recent years provided the experimental evidence for the existence of the Higgs Boson. Even though projects like CERN were scientific endeavours, they also provided a powerful political signal that European countries were committed to peaceful collaboration after a period of deep division.

This project will investigate the history of European scientific cooperation to show how science came to play such a political role. In particular, it will study the expectations, views, and ideals of a group of six scientists and administrators instrumental in shaping these developments, and how they reimagined scientific cooperation as a tool to unite Europe.

In multilingual contexts such as Luxembourg, the successful integration of immigrant children into school and society depends, among others, on their experiences and ability to cope with the multilingualism in Luxembourg. This study will focus on children from Arab, Turkish or Persian backgrounds who might find it more challenging to cope because of their different non-western linguistic and cultural backgrounds. While it is known that the parents at home, teachers at schools and policy-makers influence the children’s language use and their experiences with multilingualism, the children also play an active role in shaping their languaging practices. This study applies a qualitative methodology and explores the ways in which these immigrant children negotiate and shape multilingual experiences, express themselves, and develop linguistic identities at home, school and on social media. The findings are important for teachers, parents and policy-makers.

As a widespread risk factor for both physical and mental illness, stress represents a serious burden for the individual person concerned but also for society as a whole. In order to relief stress, many people play video games. However, research is not conclusive regarding the relationship between video games, and especially violent video games, and stress levels. There is research indicating that video games and violent video games reduce stress, but also research that suggests that video games induce stress. One of the reasons for this inconsistency in research results may be that other factors that were not addressed in prior studies might influences this relationship. Therefore, this project aims at investigating the relation between non-excessive video game play and stress, and if other factors, like personality, influences this relationship. Can video game play effectively reduce subjectively perceived and physically measurable stress levels? Are there differences between violent and non-violent video game effects on stress? Finally, which key factors (e.g. personality traits like the so-called Dark Tetrad) influence the relationship between video game play and stress? The Dark Tetrad is a combination of the personality factors of Machiavellianism (focus on dominance), psychopathy, narcissism, and sadism. In order to address these research questions, Study 1 (online survey) will provide information on gaming motives, game preferences, and personality profiles of video game users. Study 2 (lab experiment) will investigate if playing both violent and non-violent video games reduce stress levels and if personality traits influence this effect in that depending on the personality profile of players, games may have a different effect on stress levels. Study 3 (lab experiment) will test if physiological patterns after gameplay differ regarding either regulation of induced frustration or stress. This includes measuring the effect of violent video game play for recovery of physically measured stress levels after being stressed in a task prior to gameplay, as well as the potentiation of aggression after being frustrated prior to gameplay. In a last study, participants will provide systematic self-reports at random times during daily life on (for example) their stress levels and gaming hours over a period of 2 to 4 weeks. This will focus on changes in regulatory processes, behavior, and personality and will inform if video games can be used to regulate stress in everyday life effectively. In sum, the results of this project will allow (a) drawing conclusions on the effects of violent vs. non-violent video game play on subjective and objective stress levels, and (b) specifying if treatment procedures using video games could be integrated into stress interventions to combat the highly prevalent stress rates in society.

The incursion of technology into criminal justice is today an indisputable phenomenon. However, innovative justice mechanisms are still insufficiently addressed by scientific research and call for an in-depth reflection on their impact. Indeed, most criminological research interested in the digitisation of justice mainly tend to question the efficiency of new technologies while aiming at optimising the justice system’s functioning. Although such research contributes to technological improvement, it does not, however, allow us to consider in depth the transformations that take place in the very foundations of criminal justice and the evolution of its rationality. Our present research attempts to do so by addressing the fundamental dimension of the digitalisation of the criminal process and not only its technical impact. We seek to understand how this integration contributes to shaping the administration of justice, in particular regarding the conception of the legal subject, the role of the various participants in the trial, the role of the new stakeholders involved.

Tactile Internet (TI) is expected to be the next generation of the Internet of Things (IoT), which allows communication and collaboration among things without any physical boundaries. TI envisions creating a paradigm shift in enabling real-time transmission of touch and actuation (force, torque, surface texture, velocity, position) over the wired and wireless networks. And, it is expected to enable a wide range of immersive applications such as industrial automation, telesurgery, augmented reality, autonomous driving, and robotics, thus enhancing various aspects of our daily life. However, to enable real-time transmission of tactile information along with audio-visual information, future TI systems should overcome the stringent requirements in terms of ultra-low latency, ultra-high reliability, high-data-rate connectivity, resource allocation, and quality latency-reliability trade-off. In this regard, this project aims to propose intelligent architecture frameworks, flexible resource allocation algorithms, distributed learning algorithms to meet the crucial requirements of emerging TI systems over dynamic wireless networks. The developed techniques will be of significant importance to the related scientific communities in advancing future research in this domain, and also to the industries and standardization bodies in adopting them into the future standards of beyond 5G wireless systems.

We intend to develop novel framework for open-domain question-answering (QA). Current QA systems are either based on solving complex graph algorithms, or they adopt various machine learning techniques to find the best answer to a given user question. Solutions based on graph algorithms, on the one hand, do not need much training data, but are limited in terms of what kinds of questions can be matched. Solutions based on machine learning, on the other hand, can potentially find answers to more questions, but need a lot of training data (often hundreds of thousands of manually curated question-answer pairs). In this project, we therefore aim to provide the best of both worlds by combining the two into one coherent framework.

Around 90% of world’s cargo is transported on ocean ships and 60% of the world’s ocean transportation is carried in containers. However, ships are a significant source of air pollution emitting around 940 million tons of CO2 annually and these emissions are projected to increase significantly between 50% and 250% by 2050 if left unmitigated.

This PhD project looks into efficient use of capacity on the vessels to minimize harmful emissions. This PhD project seeks to understand how liner companies can collaborate to allow efficient use of maritime transport capacities in turn resulting in reduced emissions. These collaborative alliances facilitate the cooperation of companies to optimize the capacity, frequency and routes based on demand on particular routes.

Through this research study, we examine three main areas in relation to coopetition and capacity utilization. Firstly, we plan to create a system that will help us measure the emissions and capacity utilization in individual and collaborative settings. Secondly, we examine the impact of alliances in reducing emissions as opposed to operating outside alliances. Thirdly, we plan to build a model of collaboration which can also be applied to air cargo and road transport to reduce emissions in these modes of transport along with ocean transportation.

What is the impact of artificial intelligence on jobs, wages and the risk of unemployment? While in the past, software and robots have replaced middle-skill workers performing specific routine tasks, artificial intelligence has demonstrated its potential to automate both routine and non-routine tasks in a wide range of occupations and sectors. As economic theories argue that AI also has positive impacts on the labor market and on consumers, this new technology induces deep changes in the labor market which inevitably hurt those unable to adapt. Yet, evidence on the detailed impacts of AI-induced automation on wages and employment across occupations is still limited, and policies aimed at supporting workers displaced by AI need more guidance.

In this PhD project, I will provide new evidence of the impact of AI-induced automation on workers in France. The project will combine various data sources to identify how different jobs have evolved over time, what part of these evolutions can be attributed to AI, and how AI-induced changes have affected their wages and career paths. Having identified the profiles of workers who are most at risk of suffering from the introduction of AI, I will then evaluate which policies are most effective at helping displaced workers find employment again.

This PhD project is closely aligned with national and international priorities and provides an original scientific contribution to a highly relevant societal issue. It will do so by providing new evidence on the positive and adverse effects of automation and will inform policymakers in the design of new public policies.

Hyperbolic geometry, discovered by Bolyai and Lobatchevsky in the 1850s, is a cousin of Euclidean geometry which is in many ways richer. In the 1970s, W. Thurston discovered many examples of hyperbolic structures on 3-dimensional manifolds – the analogs of surfaces in dimension 3. He in fact realized that “most” 3-dimensional manifolds admit hyperbolic structures, that is, geometric structures locally modelled on the 3-dimensional hyperbolic space. Hyperbolic geometry then took a central place in contemporary geometry and low-dimensional topology.

A key feature of hyperbolic structures on closed manifolds is their rigidity: they cannot be deformed. Hyperbolic structures of finite volume on non-closed manifolds are also rigid in a suitable sense, however their holonomy can be deformed through an operation known as Dehn filling, also discovered by Thurston.
For hyperbolic manifolds of infinite volume, substantial questions remain open, for instance a pair of conjectures of Thurston on the unique determination of hyperbolic structures of a certain relatively simple type (convex co-compact structures) in terms of the induced geometry on the boundary of their convex core, the smallest non-empty geodesically convex subset that they contain. The first direction of the project will be to investigate such rigidity questions, by considering them within the larger context of the “Weyl problem” considered for unbounded convex domains in H3. The Weyl problem is a classical problem in the differential geometry of convex surfaces in Euclidean space. It was posed and answered in the first half of the XXth century, and the main results were extended to closed surfaces in the hyperbolic space. However it was noted recently that suitable extensions to unbounded surfaces in hyperbolic space contain as special cases well-known conjectures on hyperbolic structures on 3-dimensional manifolds.

A second, related direction will consider similar rigidity questions but in higher dimension. The main motivation here is a pair of papers of Kerckhoff and Storm, who on one hand provided a rigidity result for compact hyperbolic manifolds with totally geodesic boundary, and on the other found examples of 4-dimensional manifolds whose holonomy can be deformed.

A third direction will be to consider rigidity issues for higher-dimensional hyperbolic manifolds in terms of deformations of Poincaré-Einstein metrics, a type of Riemannian metric (including many hyperbolic ones) that have a rich rigidity and deformation theory.

Quantum physics and Einstein’s relativity are two of the most counterintuitive, yet fascinating theories of modern science. Their implications for our experience of time and space, and for issues such as causality and self-determination are vast, and have been the subject of ongoing debates between philosophers, physicists and mathematicians for a century. My PhD project tries to explore, clarify, and justify the origin of quantum theory in a relativistic setting by bringing powerful computer tools, thorough logic, and machine verification to the field.

The ideal scientific theory is founded on a system of axioms, which is a reasonably small list of logical assumptions. A good system of axioms is clear, succinct, and expresses formal concepts that make intuitive sense to the qualified reader. The axiomatic approach has an illustrious history in modern mathematics and mathematical philosophy, where it famously allowed people like Russell, Cantor, and Goedel to develop a rigorous foundation for mathematics, and begin to analyse the mysteries of infinity, a concept equally as mind-boggling as quantum entanglement.

Several axiom systems have been proposed for the quantum theory of particles, one of which I will focus on. The big caveat is that while several desirable properties can be proven in this axiom system, no one has managed yet to demonstrate that the most important particle physics theory, the standard model, is in fact derived from these axioms. I hope to shed some light on why that is, at the same time enabling and developing the use of computer-supported proof mechanisms in axiomatic physics.

CubeSat is one of the widely used types of small satellites which is able to endure the harsh conditions of the outer space. Indeed, if there are an appropriate number of these small satellites exploring the Earth, specific tasks which have thus far been performed by LEO (Low Earth Orbit) satellite systems, could be performed by these small satellites at a lower cost and lower energy consumption. For instance, Earth monitoring, disaster recovery, and remote surveillance are some of these important applications. Equipping these small satellites with Global Navigation Satellite Systems (GNSS) on-board receivers makes the CubeSat systems an interesting candidate to explore GNSS observations for the recovery of both static and time-variable gravity fields. Moreover, what makes CubeSats mission an interesting candidate to explore the Earth’s gravity field in terms of both static and time-variable fields, is their on-board GNSS receivers’ data which allows high spatio-temporal enhancement of the current gravity field models of the Earth. On the other hand, CubeSats which are equipped with on-board Global Navigation Satellite System (GNSS) receivers would be good candidates for precise orbit determination (POD) and the extraction of the long wave-length part of the Earth’s gravitational field. Therefore, one of the secondary objectives of the CubeSats mission can be dedicated to measure the Earth’s gravity field with the on-board GNSS hl-SST system. The GNSS observations with all the other relevant parameters can be used to determine the kinematic positions of the CubeSats based on a precise point positioning approach. The on-board GNSS receivers of the Earth observation nanosatellites (e.g. (Spire Earth observation nanosatellites) provide a unique dataset which has a high temporal and spatial resolution. Therefore, satellite remote sensing observations are beneficial to observe the large-scale (>1000 km) and short-term (<1 month) signals of the Earth’s gravity field which the GRACE mission is unable to observe due to its ground track coverage. Thus, the purpose of this research is to use the high-rate GNSS observation tracking data as an independent source to determine the Earth’s gravity field based on the CMA. In addition, it is also possible to combine the observations of non-dedicated satellite missions with those ones derived from the dedicated gravimetric missions to observe the short-term signals (<1 month) of the Earth’s gravity field model.