Estimating computational limits on theoretical descriptions of biological cells

There has been much success recently in theoretically simulating parts of complex biological systems on the molecular level, with the goal of first-principles modeling of whole cells. However, there is the question of whether such simulations can be performed because of the enormous complexity of cells. We establish approximate equations to estimate computation times required to simulate highly simplified models of cells by either molecular dynamics calculations or by solving molecular kinetic equations. Our equations place limits on the complexity of cells that can be theoretically understood with these two methods and provide a first step in developing what can be considered biological uncertainty relations for molecular models of cells. While a molecular kinetics description of the genetically simplest bacterial cell may indeed soon be possible, neither theoretical description for a multicellular system, such as the human brain, will be possible for many decades and may never be possible even with quantum computing.

An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections

ABSTRACTGiven the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia® from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) “statistical uncertainty” about the numerical value of the vaccine’s efficacy against disease, and (2) “biological uncertainty” about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia® took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccine’s public health impact.

Le interazioni fra economia e ambiente biologico nell'Europa preindustriale secc. XIII-XVIII. Economic and biological interactions in pre-industrial Europe from the 13th to the 18th centuries

Pests, parasites and pathogenic agents have exerted a notable influence on the process of economic development of pre-industrial Europe, in view of their influence on the health, longevity and reproduction of human beings, plants and animals. On each occasion man has reacted to biological uncertainty with responses that were public or private, formal or informal and differed in both efficacy and cost. Success has always been partial, and dependent on experience, knowledge and the investment of economic resources. These reciprocal influences have never been allocated an appropriate or convincing place in the institutional model or those of Smith, Malthus, Ricardo or Marx, typically exploited to describe and explain the flux and reflux of the economic development of pre-industrial Europe. In these proceedings of Study Week promoted by the Fondazione Datini, the leading experts in the sector have undertaken to analyse, exemplify and discuss the precise nature of the complex interactions between economic and biological processes and agents. Adopying a stimulating, innovative and interdisciplinary approach, they appraise the degree to which such processes acted in reciprocal independence, whether there was a significant co-evolution and what prospects there are for developing explanatory models that better grasp the essentially bilateral nature of such interactions.

Quantification of physical and biological uncertainty in the simulation of the yield of a tropical crop using present-day and doubled CO 2 climates

The impacts of climate change on crop productivity are often assessed using simulations from a numerical climate model as an input to a crop simulation model. The precision of these predictions reflects the uncertainty in both models. We examined how uncertainty in a climate (HadAM3) and crop General Large-Area Model (GLAM) for annual crops model affects the mean and standard deviation of crop yield simulations in present and doubled carbon dioxide (CO 2 ) climates by perturbation of parameters in each model. The climate sensitivity parameter ( λ , the equilibrium response of global mean surface temperature to doubled CO 2 ) was used to define the control climate. Observed 1966–1989 mean yields of groundnut ( Arachis hypogaea L.) in India were simulated well by the crop model using the control climate and climates with values of λ near the control value. The simulations were used to measure the contribution to uncertainty of key crop and climate model parameters. The standard deviation of yield was more affected by perturbation of climate parameters than crop model parameters in both the present-day and doubled CO 2 climates. Climate uncertainty was higher in the doubled CO 2 climate than in the present-day climate. Crop transpiration efficiency was key to crop model uncertainty in both present-day and doubled CO 2 climates. The response of crop development to mean temperature contributed little uncertainty in the present-day simulations but was among the largest contributors under doubled CO 2 . The ensemble methods used here to quantify physical and biological uncertainty offer a method to improve model estimates of the impacts of climate change.

SHARING THE BENEFITS OF COOPERATION IN THE NORWEGIAN SPRING-SPAWNING HERRING FISHERY

The purpose of this paper is to study the sharing of cooperative benefits between the potential fishing nations of Norwegian spring-spawning (or Atlanto-Scandian) herring (NSSH). I study a three-player coalitional game where Shapley value is used as a solution concept. The results show that full cooperation is a stable solution of the game, that is, no country finds it optimal to leave the grand coalition. However, it is further shown how full cooperation may become unstable under biological uncertainty. Therefore, I propose a simple mechanism to alleviate the problem. The instability created by biological uncertainty can be significantly reduced when simple modified cooperative strategies are applied. By introducing a safe minimum biological level for the fish stock (SMBL) below which no harvesting takes place and also changing gear selectivities, instability reduces a great deal. However, a safe minimum economic level (SMEL) when there may be perfect stability is shown to be higher than the SMBL.

Recreational Use, Valuation, and Management, of Killer Whales (Orcinus orca) on Canada's Pacific Coast

The management of many ocean wildlife species is left in an institutional void, yet certain species command considerable public attention and have burgeoning management problems. In this paper the non-consumptive recreational use of Killer Whales (Orcinus orca) on Canada's Pacific Ocean coast is used as an example of management difficulties that are associated with oceanic species. Problems associated with jurisdiction and institutional arrangements are coupled to significant levels of biological uncertainty and restricted management options, as well as to management concerns associated with the human domain. The case is conceptualized as an interaction between the human and more general ecological spheres, mediated by the history of the relationship between humans and the species in question. Two routes to regulation are presented, dealing respectively with the human and ecological aspects. Of particular significance is the idea that both types of information are necessary to maximize utility to both the human user and the Whales.Results from an ongoing study of recreational use are presented to indicate some of the variables that have emerged. These are to be interpreted within current resource management infrastructure to create a tenuous situation. The unfortunate logic that results from this study is that if Killer Whales (a high-profile species) in Canada (a well-endowed nation) have not warranted more substantial protection, then the outlook for less well-known marine species in areas of the world where resource management priorities involve more direct survival concerns, is not optimistic.