Hepatitis E virus (HEV) can cause enterically-transmitted hepatitis in humans. The zoonotic nature of Hepatitis E infections has been established in industrialized areas and domestic pigs are considered as the main reservoir. The dynamics of transmission in pig herds therefore needs to be understood to reduce the prevalence of viremic pigs at slaughter and prevent contaminated pig products from entering the food chain. An experimental trial was carried out to study the main characteristics of HEV transmission between orally inoculated pigs and naïve animals. A mathematical model was used to investigate three transmission routes, namely direct contact between pigs and two environmental components to represent within-and between-group oro-fecal transmission. A large inter-individual variability was observed in response to infection with an average latent period lasting 6.9 days (5.8; 7.9) in inoculated animals and an average infectious period of 9.7 days (8.2; 11.2). Our results show that direct transmission alone, with a partial reproduction number of 1.41 (0.21; 3.02), can be considered as a factor of persistence of infection within a population. However, the quantity of virus present in the environment was found to play an essential role in the transmission process strongly influencing the probability of infection with a within pen transmission rate estimated to 2 ⋅ 10− 6g ge− 1d− 1(1 ⋅ 10− 7; 7 ⋅ 10− 6). Between-pen environmental transmission occurred to a lesser extent (transmission rate: 7 ⋅ 10− 8g ge− 1d− 1(5 ⋅ 10− 9; 3 ⋅ 10− 7) but could further generate a within-group process. The combination of these transmission routes could explain the persistence and high prevalence of HEV in pig populations.

SUMMARYWe aim to evaluate environmental and genetic effects on the expansion/proliferation of committed single cells during embryonic development, using melanoblasts as a paradigm to model this phenomenon. Melanoblasts are a specific type of cell that display extensive cellular proliferation during development. However, the events controlling melanoblast expansion are still poorly understood due to insufficient knowledge concerning their number and distribution in the various skin compartments. We show that melanoblast expansion is tightly controlled both spatially and temporally, with little variation between embryos. We established a mathematical model reflecting the main cellular mechanisms involved in melanoblast expansion, including proliferation and migration from the dermis to epidermis. In association with biological information, the model allows the calculation of doubling times for melanoblasts, revealing that dermal and epidermal melanoblasts have short but different doubling times. Moreover, the number of trunk founder melanoblasts at E8.5 was estimated to be 16, a population impossible to count by classical biological approaches. We also assessed the importance of the genetic background by studying gain-and lossof-function b-catenin mutants in the melanocyte lineage. We found that any alteration of b-catenin activity, whether positive or negative, reduced both dermal and epidermal melanoblast proliferation. Finally, we determined that the pool of dermal melanoblasts remains constant in wild-type and mutant embryos during development, implying that specific control mechanisms associated with cell division ensure half of the cells at each cell division to migrate from the dermis to the epidermis. Modeling melanoblast expansion revealed novel links between cell division, cell localization within the embryo and appropriate feedback control through b-catenin.

This paper proposes a multiscale vision to human crowds which provides a consistent description at the three possible modeling scales, namely, microscopic, mesoscopic, and macroscopic. The proposed approach moves from interactions at the microscopic scale and shows how the same modeling principles lead to kinetic and hydrodynamic models. Hence, a unified framework is developed which permits to derive models at each scale using the same principles and similar parameters. This approach can be used to simulate crowd dynamics in complex environments composed of interconnected areas, where the most appropriate scale of description can be selected for each area. This offers a pathway to the development of a multiscale computational model which has the capability to optimize the granularity of the description depending on the pedestrian local flow conditions. An important feature of the modeling at each scale is that the complex interaction between emotional states of walkers and their motion is taken into account.