Most of the 250 millions of male piglets reared yearly in the EU are castrated by surgical means without pain prevention. Castration is performed primarily to improve meat quality and secondly to facilitate management. Indeed, pigs for meat production are usually slaughtered when testes are well developed and secrete sex steroids at the origin of boar taint, a specific taste of the meat rejected by consumers, and of behavioural problems linked to mounting and aggressive behaviours. Following the general trend of the society for a better recognition of animal sentience, there is an increasing pressure for banning surgical castration. In addition to avoiding suffering of piglets due to surgical castration, raising entire males may have positive effects on the environment since the food conversion of entire males is more efficient (about 10%). A positive influence of testicular hormones on health is also suspected. Another alternative to surgical castration would be to perform immuno-castration which consists of vaccinating the animals against reproductive hormones a few weeks before slaughter. Immuno-castrated animals benefit from the testicular hormones during most of their life and their feed conversion efficiency is intermediate between surgically castrated and entire males. The aim of the present project is to acquire more knowledge on the development of the behaviour, physiology and nutrient requirements of entire and immuno-castrated pigs to take advantage of their positive characteristics and to reduce the impact of their negative ones. The project will be divided into four tasks focusing on the influence of testicular hormones on behaviour (Task 1), on the hypothalamo-pituitary-adrenal (HPA) axis and sympathetic nervous system (Task 2), on the immune function and health (Task 3) and on the nutrient utilization (Task 4). Since the underlying physiological mechanisms of sexual development are connected, we will analyse the interactions between systems and functions. In each task, we will compare entire males, males surgically castrated early in life and males immuno-castrated during puberty (subjected to sex hormones for a large period of their life). Therefore, we will be able to determine short and long-term effects of testicular hormones. According to the present knowledge on the different aspects, we will follow the development of the pigs or focus on the actual slaughter age of fattening pigs. In addition, for Tasks 1-3, we will vary the housing as a possible solution for reducing the negative effects of sexual development since it may affect deeply the behaviour, HPA axis and immune system. For Task 1, animals will be observed either in their rearing environment, during controlled tests outside their home pen and at the slaughter house. Animals will be fitted with ear transponders to analyze feeding behaviour by telemetry. For Task 2, animals will be submitted either to single samplings (in blood, saliva and/or urine) at various ages or to serial blood samplings via a permanent catheter after a hormonal challenge or an acute stressor. Concentrations of hormones or their metabolites from the HPA axis and SNS will be measured. For Task 3, we will evaluate various dimensions of the immune system using blood cell numeration, in vitro tests of lymphocytes proliferation, analysis of lymphocytes subtypes by cytometry, IgG response to an immune challenge. Health of the animals will be evaluated by measurement of blood concentrations of proteins indicative of inflammatory reactions and by clinical examination of the viscera from slaughtered animals. In Task 4, we will measure circulating levels of hormones and nutrients with single samples collected at various ages or serial blood collected at one age in catheterized animals. In addition, we will evaluate energy and protein utilization by measurements in metabolic chamber. For Tasks 2-4, level of expression of receptors or enzymes from the HPA axis (in adrenals and liver), receptors to sex hormones (in liver, adrenals, muscle and lymphoid organs), receptors or hormones from the somatotropic axis (liver and muscle) will be measured in tissue samples collected in slaughtered animals. We expect that some of these results regarding the effects of testicular hormones on the behaviour and the physiology may apply to numerous mammalian species especially those characterized by a pubertal development similar to pigs. Some other results, for instance those regarding the handling easiness of pigs, the effect of housing or the nutrient requirements, will be more specific to pigs. These results will contribute to remove breaks to the production of entire and immuno-castrated pigs that may improve animal welfare and reduce environmental problems.

Since 1998, obesity has been considered by World Health Organization to be a disease spreading in an epidemic way. Currently, obesity affects nearly 20 to 50% of the world population. Eventhough all social classes of the population are affected, it appears to predominate in classes having low economic income, and is not restricted to developed countries. This pathology represents a proven factor for the development of type II diabetes and several cardiovascular diseases. Existing therapies based on drug delivery or surgery exhibit a limited effectiveness in comparison to their high invasivity and reduced adaptability. Some researches focused on the study of the vagal nerve have demonstrated its important role in nervous signals addressed to the hypothalamus for satiety regulation. This has promoted exploration in the field of vagal nerve electrostimulation in order to induce satiety (and thus weight reduction) for people suffering severe and morbid obesity. The SAVANE project presents the experimental development of a complete vagal nerve stimulator system, implantable by cœlioscopy and intended to obesity treatment. Indeed, a treatment method using vagal nerve stimulation and having both advantages of reversibility and adaptability has been successfully experimented on a pig at the National Institute of Agronomic Research of Rennes (France). This work has led to the deposit of an international request of patent, on August 28th, 2007. The similarity between pigs and humans' anatomy,particularly considering their respective digestive apparatus, enables scientists to extrapolate the experimental methodology and subsequent results to Human Being. Nevertheless, the employed exploratory method may not be directly implementable to humans due to both the invasiveness of the surgical technique (laparotomy) and the inadequacy of the device's architecture. The primary objective of the project will be the technical validation on a pig, of the complete system intended to be implanted by cœlioscopy. The secondary one will be devoted to the validation of the stimulation strategy planned for obesity treatment. In a near future, the complete valorisation of the project will consist in a successful transfer and validation of the entire system (stimulator and stimulation procedure) to the human being. Indeed, for evident reasons of detachment, the human validation part will not be included in this study.

The neurobiological bases of filial attachment are still poorly known, in contrast to the extensive work done on maternal behaviour. Sheep are precocial mammals developing mutual mother-young recognition. The fact that lambs can develop a strong bond with their dam makes them suitable for the study of filial attachment. Lambs have the ability to bond both to their dam and to humans but the neurobiological mechanism may be dissimilar. As OT is known to play a major role in social behaviours, the aim of our project is to examine to what extend the OXTergic system participates in the physiological and neurobiological mechanism mediating homo- and hetero-specific attachment responses. We hypothesise that the release of OXT will be triggered by the mere presence of the mother, but that in the case of the humans, additional somatosensory stimulation such as touch will be necessary. Such additional stimulation from the mother (nosing, body contact) should also potentiate the release of OXT. We will use the separation-reunion paradigm developed by Ainsworth (1989) in human infants and adapted for animals. Under such experimental conditions, subjects are soothed by the presence of their partner and distressed when isolated. In addition, knowing that (i) positive interactions with the attachment figure promotes calmness and (i) OXT is proposed as a mediator for well-being, we will test the hypothesis that calming stimuli provided by the attachment figure decrease heart rate and cortisol levels, activate specific brain structures, and that most of the behavioural and physiological responses can be attenuated by OXT antagonists. General experimental situation ' At birth, lambs will be either left with their mother or they will be separated and reared artificially with powdered milk. In the second situation, a specific person will take care of a specific group of lambs to favour the development of hetero-specific attachment. ' On week 1, lambs will be submitted to a two-choice test in order to determine the existence of a preference for the attachment figure (ewe or human). ' On week 2, neurosurgery will be performed on lambs used in Task.1 to implant an intracerebroventricular cannula for subsequent collection of cerebrospinal fluid. ' On week 4 to 6, lambs will be allocated to one of the three following groups: o (i) tested with their attachment figure (no somatosensory stimulation), then isolated, and lastly tested after reunion with the attachment figure (no somatosensory stimulation). Each phase of the test lasts 30 min making a total of 90 min for the whole testing session. Proximal interaction will be prevented by a double layer fence (50 cm apart), the human will sit still. Main hypothesis: OXT is more likely to be released in the presence of the mother; o (ii) tested in the same situation as above but with somatosensory stimuli provided by the attachment figure (both partners can interact: body-to-body contact with mother, nosing, sniffing; stroking with human). Main hypothesis: OXT is released in both cases, response potentiated by nosing/stroking in comparison to previous situation. o (iii) tested in isolation. Main hypothesis: no change in OXT levels; o These three situations may be repeated according to experimental needs. Specific aims of the proposal ' Task 1. Subtask 1.1 is a crucial descriptive step that will give valuable correlative information between central-peripheral OXT release and (1) the distressed state induced by isolation, (2) the calm state induced by the mere presence of the attachment figure, (3) the calm stated induced by somatosensory stimuli provided during positive interactions with the attachment figure (and plasma cortisol and heart rate variation). Subtask 1.2 will characterize neuronal activation during interactions with the attachment figure which will include, or not, additional somatosensory stimulation (mother: nosing; human: stroking). ' Task 2 will aim at determining the sites and dynamic of action of OXT with the use of gamma cameras and scintigraphy. ' Task 3 will aim at quantifying in deeper details the behavioural responses of lambs when interacting with their attachment figure. Based on results from Subtask 1.1, specific times in regards to the separation-reunion situation will be chosen to take blood samples and correlate OXT, cortisol levels, and heart rate variation with the intensity of the interactions. ' Task 4 will test the hypothesis of the involvement of the OXTergic system in the expression of calmness. The effects of the antagonist will be tested when lambs will be with their attachment figure. Social bonds, e.g. the relationship between the responses displayed by lambs in the absence or the presence of their attachment figure and OXT will be studied with an interdisciplinary approach at 7 levels: 1) Behaviour 2) Physiology; 3) Neurophysiology 4) Neuroendocrinology 5) Neurobiology 6) Functional brain imaging 7) Pharmacology

The IoT will contain a huge number of devices and objects that have very low or nonexistent processing and communication resources, coupled to a small number of high-power devices. The weakest devices, which are most ubiquitous, will not be able to authenticate themselves using cryptographic methods. Other important tasks in the IoT will be to verify if an object is authentic, or to identify an object. Our plan is to address these issues using Physical Unclonable Functions (PUFs). PUFs, and especially Quantum Readout PUFs, are ideally suited to the IoT setting because they allow for the authentication and identification of physical objects without requiring any crypto or storage of secret information. Furthermore, we foresee that back-end systems will not be able to provide security and privacy via cryptographic primitives due to the sheer number of IoT devices. Our plan is to address these problems using privacy-preserving database structures and algorithms with good scaling behaviour. Approximate Nearest Neighbour (ANN) search algorithms, which have remarkably good scaling behaviour, have recently become highly efficient, but do not yet have the right security properties and have not yet been applied to PUF data. Summarised in a nutshell, the project aims to improve the theory and practice of technologies such as PUFs and ANN search in the context of generic IoT authentication and identification scenarios.

The IoT has a great potential to provide novel services to humans in critical areas for society. This innovation however requires updating our understanding of the risks associated with the new technology so that we can deploy it with confidence and society can trust it. Amongst the biggest problems for this vision to become a reality are security flaws due to technical restrictions, immaturity of software applications, intrusion threats through new challenges in complex usage scenarios, and mainly a lack of transparency. The IoT could become human centric computing that serves our society, but simultaneously amongst the main triggers for security problems is human behaviour, either unintentionally or maliciously. The core idea of SUCCESS is to use methods and tools with a proven track record to provide more transparency of security risks for people in given IoT scenarios. Our core scientific innovation will consist on the extension of well-known industry-strength methods in our priority areas. Our technological innovation will provide adequate tools to address risk assessment and adaptavity within IoT in healthcare environments and an open source repository to foster future reuse, extension and progress in this area. Our project will validate the scientific and technological innovation through pilots, one of which will be in collaboration with a hospital and will allow all stakeholders (e.g. physicians, hospital technicians, patients and relatives) to enjoy a safer system capable to appropriately handle highly sensitive information on vulnerable people while making security and privacy risks understandable and secure solutions accessible. This innovation will be achieved by a multi-disciplinary team of recognized experts in their fields which has significant experience in knowledge transfer to and from society. SUCCESS will have significant impact, strengthening the interdisciplinary approach to this important challenge at the crossroads between society and technology, creating new methods for increased security in healthcare, supporting the use of these robust methods by adequate open-source tools, and educating on the use of our products through real-life working prototypes.