One of the most promising strategies to treat cancer is attacking it with viruses. Oncolytic viruses can kill tumor cells specifically or induce anticancer immune response. A multiscale model for virotherapy of cancer is investigated through simulations. It was found that, for intratumoral virus administration, a solid tumor can be completely eradicated or keep growing after a transient remission. Furthermore, the model reveals undamped oscillatory dynamics of tumor cells and virus populations, which demands new in vivo and in vitro quantitative experiments aiming to detect this oscillatory response. The conditions for which each one of the different tumor responses dominates, as well as the occurrence probabilities for the other nondominant therapeutic outcomes, were determined. From a clinical point of view, our findings indicate that a successful, single agent virotherapy requires a strong inhibition of the host immune response and the use of potent virus species with a high intratumoral mobility. Moreover, due to the discrete and stochastic nature of cells and their responses, an optimal range for viral cytotoxicity is predicted because the virotherapy fails if the oncolytic virus demands either a too short or a very large time to kill the tumor cell. This result suggests that the search for viruses able to destroy tumor cells very fast does not necessarily lead to a more effective control of tumor growth.

Animal movements have been related to optimal foraging strategies where self-similar trajectories are central. Most of the experimental studies done so far have focused mainly on fitting statistical models to data in order to test for movement patterns described by power-laws. Here we show by analyzing over half a million movement displacements that isolated termite workers actually exhibit a range of very interesting dynamical properties –including Lévy flights– in their exploratory behaviour. Going beyond the current trend of statistical model fitting alone, our study analyses anomalous diffusion and structure functions to estimate values of the scaling exponents describing displacement statistics. We evince the fractal nature of the movement patterns and show how the scaling exponents describing termite space exploration intriguingly comply with mathematical relations found in the physics of transport phenomena. By doing this, we rescue a rich variety of physical and biological phenomenology that can be potentially important and meaningful for the study of complex animal behavior and, in particular, for the study of how patterns of exploratory behaviour of individual social insects may impact not only their feeding demands but also nestmate encounter patterns and, hence, their dynamics at the social scale.

The shape of large on-lattice Eden clusters grown from a single seed is ruled by the underlying lattice anisotropy. This is reflected on the linear growth with time of the interface width (w ∼ t), in contrast with the KPZ universality class (w ∼ t 1/3 ) observed when the Eden model is grown on flat substrates. We propose an extended Eden model, in which the growth probability has a power law dependence with the number of occupied nearest neighbors. Large scale simulations (N 4 × 10 9 particles) were used to determine the time evolution of w. We found that a suitable choice of the power exponent removes the lattice-induced cluster anisotropy and provides a growth exponent in very good agreement with the KPZ universality class. Also, the present model corroborates the results found in off-lattice simulations, in which the center of mass fluctuations are considered in the interface scaling analysis.

As the number or density of interacting individuals in a social group increases, a transition can develop from uncorrelated and disordered behavior of the individuals to a collective coherent pattern. We expand this observation by exploring the fine details of termite movement patterns to demonstrate that the value of the scaling exponent μ of a power law describing the Lévy walk of an individual is modified collectively as the density of animals in the group changes. This effect is absent when termites interact with inert obstacles. We also show that the network of encounters and interactions among specific individuals is selective, resembling a preferential attachment mechanism that is important for social networking. Our data strongly suggest that preferential attachments, a phenomenon not reported previously, and favorite interactions with a limited number of acquaintances are responsible for the generation of Lévy movement patterns in these social insects.

One of the most promising strategies to treat cancer is attacking it with viruses designed to exploit specific altered pathways. Here, the effects of oncolytic virotherapy on tumors having compact, papillary and disconnected morphologies are investigated through computer simulations of a multiscale model coupling macroscopic reaction diffusion equations for the nutrients with microscopic stochastic rules for the actions of individual cells and viruses. The interaction among viruses and tumor cells involves cell infection, intracellular virus replication and release of new viruses in the tissue after cell lysis. The evolution in time of both viral load and cancer cell population, as well as the probabilities for tumor eradication were evaluated for a range of multiplicities of infection, viral entries and burst sizes. It was found that in immunosuppressed hosts, the antitumor efficacy of a virus is primarily determined by its entry efficiency, its replicative capacity within the tumor, and its ability to spread over the tissue. However, the optimal traits for oncolytic viruses depends critically on the tumor growth dynamics and do not necessarily include rapid replication, cytolysis and spreading currently assumed as necessary conditions to a successful therapeutic outcome. Our findings have potential implications on the design of new vectors for the viral therapy of cancer.

Abstract. Oncolytic virotherapy -the use of viruses that specifically kill tumor cells -is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In the present work, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8 + T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.

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Behavioral lab bioassays involving termites must be promptly performed to allow intended observations prior to death from dissecation, typical of these soft-bodied insects. To this end, topic markers have been proposed as an alternative to histological stains which, while not always toxic are inevitably lengthy to apply. Among recommended topic markers, gouache is easy to apply, dries out quickly, but it is known affect termites in the long run, being suitable only to short-term bioassays. Its alternative, colored glue, is also easy to apply, but it takes long to dry and it is too dense and heavy, being thus prone to affect termite walking patterns. Here we tested a mix of gouache and colored glue aiming to combine the qualities of both into a suitable topical marker for Cornitermes cumulans termites. Similar patterns of survival presented by marked and unmarked termites ruled out concerns about toxicity of this mixture. Such results were consistent across distinct group densities evidencing that the mixture does not interfere with, nor it is affected by, crowding effects. Because crowding regulates interindividual interactions and these underlie most behaviors, the mixture can be thought to be suitable to behavioral studies. We argue that this 1:2 glue:gouache mixture is an excellent alternative to mark termites for lab bioassays. Being atoxic, cheap, easy to apply, and non-invasive, this mixture may happen to be useful not only for termites but also in bioassaying other similarly soft-bodied insects.