Herpesviruses cause serious diseases in humans and animals. After initial lytic infection, herpesviruses establish a quiescent (latent) infection, which allows their persistence in the host for life. We and others recently identified a novel mechanism that allows maintenance of the genome of certain herpesviruses during latency, by integrating their complete genetic material into host telomeres. One of these viruses is human herpesvirus 6 (HHV-6) which is associated with seizures, encephalitis, and graft rejection in transplant patients. Sporadic reactivation of the integrated virus ensures continued evolution of the virus as it spreads to a new cadre of susceptible individuals. There are critical gaps in our knowledge regarding the fate of herpesvirus genomes during integration and reactivation as well as of viral and cellular factors involved in these processes. INTEGHER will make use of novel technologies to close these gaps and to devise new therapeutic approaches. Specifically, we will 1) determine the fate of the HHV-6 genome during latency by developing a novel reporter system that allows live-cell imaging of the virus genome in living cells and elucidate epigenetic changes of the HHV-6 genome during integration and reactivation; 2) identify viral and cellular factors that drive virus genome integration and reactivation, using recombinant viruses, drugs and CRISPR/Cas9 genome engineering 3) employ genome-editing tools to eliminate the virus genome integrated in host chromosomes in vitro and in an in vivo model. The proposal utilizes state-of-the-art technologies and pioneers new approaches, particularly with regard to visualization and excision of virus genomes in latently infected cells that are also present in (bone marrow) transplants. Altogether, these studies will define the mechanism of herpesvirus integration and reactivation and will provide new tools for therapeutic excision of virus genomes from living cells.

Through the lens of ‘shared and equal parenting’, DEMFAM studies the transformation of gender and the family in contemporary global history. First, it studies a shift from hierarchical to egalitarian conceptions of family relations, or a democratisation of the family. This entails the equalisation of parental rights within and outside the domain of heterosexual marriages, which coincided with the harmonisation of the rights of marital and non-marital children. The emergence of post-familial care arrangements, secondly, led to a denser regulation, or juridification of co-parenting. Inner-familial power shifts were accompanied by a reconfiguration of family-state relations. The project investigates the development of judicial and extra-judicial institutions (including family courts, social work interventions, and mediation agencies) which aimed to promote parental cooperation and safeguard child welfare in familial conflict situations. Finally, it shows how parental rights assumed centre stage in the twenty-first century’s ‘gender wars’, or the politicisation of gender, sexuality, and the family in struggles over national and religious identity, liberalism, and democracy. DEMFAM analyses these (limited and contradictory) transformative processes across different political-economic and legal systems within a shared global environment. The project develops a social history of law reform on different political scales to understand global dynamics of divergence and convergence in the transformation of gender and the family. It combines the analysis of transnational knowledge circulation (including policy transfer, civil society mobilisation, and scientific expertise) with the comparative study of family change in Western Europe (FRG, UK), Central Eastern Europe (the GDR, Poland), and South Asia (India). Integrating research on post-colonial legal pluralism, and on (post-)socialist gender and family politics, DEMFAM opens new horizons for global gender history.

Traditional complexity theory focuses on the dichotomy between P and NP-hard problems. Lately, it has become increasingly clear that this misses a major part of the picture. Results by the PI and others offer glimpses on a fascinating structure hiding inside NP: new computational problems that seem to lie between polynomial and NP-hard have been identified; new conditional lower bounds for problems with large polynomial running times have been found; long-held beliefs on the difficulty of problems in P have been overturned. Computational geometry plays a major role in these developments, providing some of the main questions and concepts. We propose to explore this fascinating landscape inside NP from the perspective of computational geometry, guided by three complementary questions: (A) What can we say about the complexity of search problems derived from existence theorems in discrete geometry? These problems offer a new perspective on complexity classes previously studied in algorithmic game theory (PPAD, PLS, CLS). Preliminary work indicates that they have the potential to answer long-standing open questions on these classes. (B) Can we provide meaningful conditional lower bounds on geometric problems for which we have only algorithms with large polynomial running time? Prompted by a question raised by the PI and collaborators, such lower bounds were developed for the Frechet distance. Are similar results possible for problems not related to distance measures? If so, this could dramatically extend the traditional theory based on 3SUM-hardness to a much more diverse and nuanced picture. (C) Can we find subquadratic decision trees and faster algorithms for 3SUM-hard problems? After recent results by Pettie and Gronlund on 3SUM and by the PI and collaborators on the Frechet distance, we have the potential to gain new insights on this large class of well-studied problems and to improve long-standing complexity bounds for them.

This action supports physical and blended mobility of higher education students and staff from EU Member States and third countries associated to Erasmus+ to any country in the world. Students in all study fields and cycles can take part in a study period or traineeship abroad. Higher education teaching and administrative staff can take part in professional development activities abroad, as well as staff from the field of work in order to teach and train students or staff at higher education institutions.

Multiple causal modelling techniques are employed in the applied sciences. For instance, Structural Equations Models (SEMs) are employed in genetics, econometrics and psychology; Fault Tree Analyses (FTAs) are employed in aerospace and nuclear engineering; Petri Nets are used in traffic control and integrated computational systems. Each technique has a unique way of representing causal phenomena, drawing on different data and background information. But what is it about the world that allows each of these techniques to work? And what makes each technique a representation of causal phenomena specifically? POCAM will break new ground answering these questions by determining a single, underlying causal ontology within the powers metaphysics framework. In doing so, POCAM will provide an explanation of why such varied causal modelling practices are so successful, thereby helping practitioners better conceptualise the connections among different modelling formalisms and with our pre-scientific understanding of causation in everyday life. While there have been attempts to determine an underlying ontology for SEMs there has yet to be any philosophical engagement with FTAs or Petri Nets, despite their pervasiveness in science. Moreover, current ontologies for causal models in metaphysics fail to be adequately reductive, preventing them from being truly explanatory. POCAM will therefore be pioneering in its attempt to provide a single reductive ontology of all three modelling techniques. To do so, POCAM will draw on the scientific credentials of the powers metaphysics framework. The nature of powers and their role in causation is increasingly well understood but has yet to be brought into sustained theoretical engagement with the casual modelling literature. Dr Friend’s unique expertise, as a philosopher of science and trained engineer, will enable him, aided by expert scientific advice and supervision, to carry out this inter-disciplinary research.