In many settings of practical concern a close connection exists between the expertise held within a group of individuals and individuals' selfish interests, which may prevent the expertise from being offered in an impartial way. Examples of this phenomenon can be found in scientific peer review, which is based on the very idea that the quality of scientific work is best judged by peers of the scientist or scientists carrying out the work, in peer grading, where students on a course assess the work of other students and thus relieve pressure on teachers and enable better quality teaching or larger class sizes, and in the appraisal of employee performance, which relies on reports from other employees to make decisions regarding bonus payments or promotions. In all of these examples we are interested in aggregating individuals' impartial assessment concerning other members of the group into a collective judgment, but honest reporting may be compromised by selfish interests: the interest of a scientist to receive funding for scientific work and publish the results of this work, the interest of a student to do well on a course, or the desire of an employee to receive a bonus payment or be promoted. As it is often reasonable to assume that individuals will provide impartial assessments as long as they cannot influence the resulting judgment about themselves, it makes sense to consider what we call impartial mechanisms for aggregating individuals' reports, procedures that select an outcome in such a way that truthful reporting is in each individual's best interest. The mathematical study of impartial mechanisms is part of the area of mechanism design in microeconomic theory, and specializes the larger class of incentive-compatible mechanisms to settings where reports amount to an assessment of the members of a group and the preferences of an individual only concern the collective judgment of that individual. The study of impartial mechanisms is relatively new and only a small literature exists on such mechanisms, specifically for the allocation of a fixed amount of a divisible resource and the selection of a fixed number of individuals. The proposed project sets out to rigorously study optimal impartial mechanisms for a larger class of settings: selection with and without abstentions and with or without intensities, assignment, and ranking. An impartial mechanism is called optimal in this context if among all impartial mechanisms it maximizes the overall quality of the solution. New mathematical insights regarding impartiality will be used to develop new practical mechanisms for real-world problems of peer review, peer grading, and performance appraisal. These mechanisms will be tested and made available to the public as part of a free online service, which will also be used to investigate real-world impartiality requirements and new application areas.

More than 80 % of the living animal species are arthropods, with over a million modern species described and a fossil record reaching back to the late proterozoic area. Arthropods are common throughout marine, freshwater, terrestrial, and even aerial environments. They include four groups: insects (e.g. flies and beetles), crustaceans (e.g. shrimps and lobsters), chelicerates (e.g. spiders and scorpions) and myriapods (e.g. millipedes and centipedes). There is a long-standing debate on the internal relationships of arthropods. Traditionally, myriapods were thought to be the closest relatives of insects. However, recent comparison of the sequences of similar genes in all arthropod groups resulted in a different hypothesis: insects are more closely related to crustaceans than to myriapods. Interestingly, data on the development of the nervous system in all four groups support this hypothesis and in addition even support a close relationship of chelicerates and myriapods. In contrast to insects and crustaceans, neural stem cells that divide and generate all the cells of the nervous system are absent in chelicerates and myriapods, rather, the area from which the nervous system develops consists of many more cells that directly develop into nerve cells. Despite these differences similar genes control the formation of the nervous system in insects, chelicerates and myriapods. However, their activity and function is adapted to the specific mode of nervous system formation. Crustaceans show the greatest diversity in shape and development among arthropods and therefore it is not clear if all crustacean groups share a common ancestor or if some groups, like the higher crustaceans (e.g. crabs, lobsters), are more closely related to insects while others are not. In addition, the similarities to insects have only been demonstrated in higher crustaceans. Except for two genes, neural development genes have not been identified in crustaceans yet. In the proposed project we will therefore analyse two representatives of crustaceans, the higher crustacean or malacostracan, Orchestia cavimana (a shrimp-like crustacean) and the basal branchiopod, Daphnia magna (a water flea). We will analyse the whole process of nervous system development from the generation of neural stem cells up to the formation of neural networks. On the one hand we will identify genes that are involved in the generation of neural stem cells and study their activity and function. On the other hand, we will verify if neural stem cells are present in the water flea and compare the number and positions of individual stem cells to Orchestia and to insects. Furthermore, we will analyse which nerve cells and support cells are generated by individual stem cells in both crustaceans by single cell labelling of neuroblasts that are adjacent to the ventral midline. In addition, this method will enable us to study the formation of neuronal networks, since the whole cell bodies including the long thin processes that connect individual nerve cells are labelled. The proposed project will (1) contribute substantially to our knowledge on crustacean neurogenesis, (2) contribute to the resolution of arthropod relationships and (3) contribute to the understanding in what way the developmental mechanisms leading to the formation of the nervous system have been modified during evolution in the individual arthropod groups.

The proposed research will lead to a book entitled The Love of Strangers: Literary Cosmopolitanism in the English 'Fin de Siècle', as well as to two workshops and an international conference designed to explore cosmopolitanism within and beyond the specific historical context of the 1890s.Throughout, I aim to show that knowing how cosmopolitanism was understood in the 1890s can enhance our understanding of, and participation in, the debates around national identity and globalisation that are current in our own day. Cosmopolitanism, derived from the ancient Greek for 'world citizenship', offers a radical alternative to the ideology of nationalism, asking individuals to imagine themselves as part of a global community that goes beyond national and linguistic boundaries. The 1890s witnessed a widespread public debate on cosmopolitanism: in Britain and throughout Europe, this period saw a clash between ideologies of trans-national cooperation and universalism, partly promoted by modern transport and communication technologies, and the rising nationalism that would culminate in the First World War. My research will show that the 1890s controversy around cosmopolitanism, largely uncharted so far, is a shaping influence on the literary culture of this decade which has long been recognised as a crucial turning point in literary history. Promoters of literary cosmopolitanism questioned the supposedly fundamental link between literature, national identity, and national language: they deliberately sought out the strange and foreign in their works in order to create new ways of reading and writing that crossed boundaries between languages and literary genres as much as between different nations. These practices were denounced as politically and morally suspect by the detractors of cosmopolitanism, who stressed the responsibilities of literature towards local communities and the nation. I aim to show that a nuanced and historically-accurate understanding of the debate on cosmopolitanism transforms our understanding of the literary culture of the fin de siècle, allowing us to move beyond the categories of decadence, impressionism, and symbolism that have dominated the critical tradition. In order to do so, I concentrate on authors who embrace the cosmopolitan ideal but are also careful to define what is at stake in the controversy surrounding it. My monograph will therefore be divided into five chapters that examine, respectively: Oscar Wilde; George Egerton (Mary Dunne Bright); Ouida (Maria Louise Ramé); John Addington Symonds and Havelock Ellis; and Henry James. Drawing mainly on articles in the periodical press, the introduction will aim to reconstruct the meaning and associations of the term 'cosmopolitanism' for readers in the 1890s, teasing out its literary implications; while the conclusion will relate the 1890s debate on cosmopolitanism to our current discussion about global/local identities. My case studies have been chosen in order to break down existing distinctions between canonical and marginal writers, 'high' and popular literature, male and female authorship. I will show that the debate on cosmopolitanism involved authors and readerships with very different aesthetic and political agendas. Each chapter draws both on published and archival material in order to piece together literary networks that connect English works from this period with a range of French, Scandinavian, Italian, and German sources. A particularly original aspect of my approach is the emphasis on gender: I argue that politically and socially marginalised groups such as women and homosexual men were drawn to the cosmopolitan ideal as a utopian path towards artistic and personal freedom; and conversely, that cosmopolitanism, with its attack on traditional models of national identity, generated new ways of understanding the body, gender, and sexual identities.

Chloroplasts and mitochondria are normal components of many cells - they are sub-cellular structures called organelles. Interestingly, these two organelles evolved from bacteria that were engulfed by other cells over a billion years ago, and in many ways they still resemble free-living bacteria. Chloroplasts are found in plant cells, contain the green pigment chlorophyll, and are responsible for the reactions of photosynthesis (the process that captures sunlight energy and uses it to power the activities of the cell). Since photosynthesis is the only significant mechanism of energy-input into the living world, chloroplasts are of inestimable importance, not just to plants but to all life on Earth. Actually, chloroplasts belong to a wider family of related organelles called plastids. Other members of the family are the highly-pigmented chromoplasts in ripe fruits, and etioplasts in dark-grown plants. Although plastids do contain DNA (a relic from their evolutionary past as free-living photosynthetic bacteria), and so can make some of their own proteins, most of the proteins needed to form a functional plastid are encoded on DNA in the cell nucleus; these proteins are made outside of the plastid in the cellular matrix known as the cytosol. As plastids are each surrounded by a double membrane, or envelope, that is impervious to the passive movement of proteins, this presents a significant problem. To overcome the problem, plastids evolved a sophisticated protein import apparatus, which uses energy (in the form of ATP) to drive the import of proteins from the cytosol, across the envelope, to the plastid interior. This import apparatus comprises two molecular machines: one in the outer envelope membrane called TOC (an abbreviation of "Translocon at the outer envelope membrane of chloroplasts"), and another in the inner envelope membrane called TIC. Each machine is made up of several different proteins which cooperate to ensure the efficiency of import. We work on a model plant called Arabidopsis that has many advantages for research, such as an availability of numerous mutants (each one with a mutation in a specific gene). One such mutant plant, ppi1, has a defect in a TOC gene such that plastid protein import does not work efficiently. Several years ago, we identified another mutation called sp1 (this stands for "suppressor of ppi1") that counteracts the negative effects of ppi1. The gene disrupted by sp1 (the SP1 gene) encodes a type of regulatory protein called a "ubiquitin E3 ligase". These work by labelling-up unwanted proteins and targeting them for removal. Because this control mechanism was not previously known to operate in plastids, this discovery was an important breakthrough in biology. The SP1 E3 ligase carefully controls the composition of the TOC machinery so that the right proteins are always imported (this is normally good, but in the abnormal ppi1 background it is apparently a hindrance). Such control is very important when plastids need to convert from one form to another; e.g. when dark-germinated plants emerge into the light, etioplasts must change into chloroplasts so that photosynthesis can begin. In this project we will investigate whether SP1 is important for the conversion of chloroplasts into chromoplasts in tomato fruit. If it is, then our work may have commercial, agricultural importance by enabling the manipulation of fruit ripening in crops (e.g. tomato, bell pepper, citrus). We will also study in much greater detail how SP1 and related proteins control plastid development. For example, our work may elucidate how plants respond to stresses like salinity and drought, which are major limits on crop yield across the world. Photosynthetic performance (and thus the energy available to plants for growth) is strongly affected by stress, and we suspect that SP1 is involved in this process. Thus, knowledge gained from our work may enable improved adaptation of crops to adverse environmental conditions.

Pluripotent stem cells can differentiate into all adult cell types. Understanding how pluripotent stem cells differentiate into many different mature cell types is a key question for the biomedical and regenerative sciences. The regulation of gene activity is key for stem cells and differentiation. In the nucleus, histones and other molecules wrap the genetic material in a substance called chromatin. The accessibility of DNA within chromatin is of fundamental importance: chromatin "opens" to allow gene activity and "closes" to shut it down. Microscopy studies very early on showed that stem cells have relatively open chromatin while fully mature cells have large closed regions instead. We currently think that pluripotent stem cells achieve differentiation into many different cell types by opening and closing of different regions of their genomes in each type. In the last decade, we have made great advances to understand these opening and closing events in part thanks to the development of techniques that measure chromatin accessibility and interactions across the entire genome, and have elucidated the events that characterize differentiation to a few cell types in vitro. We have also discovered that alterations in these events often lead to cancer and disease. However, we still do not understand how pluripotent stem cells orchestrate their chromatin opening and closing events to unfold the differentiation programs of the myriad of mature cell types that make a complex adult organism. To tackle this question, I propose to measure chromatin interactions and accessibility at the single cell level in the planarian Schmidtea mediterranea, an ideal model organism through which we can investigate pluripotent stem cell differentiation in vivo. Freshwater planarians are invertebrates that, unlike us, have pluripotent stem cells as adults. They constantly differentiate into all cell types to replace damaged cells and to enable the remarkable planarian regeneration properties: each piece from a planarian can regenerate an entire adult in a matter of days. Recent technological advances of single-cell analysis together with the properties of planarians as a model organism enable this research now. We have already implemented single-cell approaches into planarians, resulting in the elucidation of the complete differentiation tree of planarian stem cells. Here I propose to use novel single-cell techniques to measure chromatin structure and accessibility in planarian cells. This will tell us which regions of the planarian DNA and chromatin open or close in every stage of differentiation to each of the major planarian mature cell types. We can also turn off several genes that are likely to be regulating this process and measure chromatin accessibility in these animals. Most of these genes are present in both humans and planarians and we know that stem cells from both need them to function both but we still ignore their precise mechanisms of action. By measuring how chromatin accessibility changes after turning them off we will understand which are the opening and closing events that they regulate and in which cell types they are important. This information will enable new strategies for human stem cell differentiation approaches and regenerative medicine by targeting those same genes. Altogether, this research will allow us to understand how stem cells reshape their chromatin to differentiate into multiple and different mature cell types.