Development and validation of computational models of cellular interaction

In this paper we take the view that computational models of biological systems should satisfy two conditions – they should be able to predict function at a systems biology level, and robust techniques of validation against biological models must be available. A modelling paradigm for developing a predictive computational model of cellular interaction is described, and methods of providing robust validation against biological models are explored, followed by a consideration of software issues

Agent-based computational modeling of wounded epithelial cell monolayers

Computational modeling of biological systems, or ‘in silico biology’ is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500mm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09mM) [Ca2+] was approximately twice as rapid as in physiological (2mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in S-phase would be expected, and this conclusion was supported experimentally in vitro by BrdU incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures

Comparative Growth Rates of Different Strains of Rhizobium meliloti

The growth rates of two strains of Rhizobium meliloti were measured when the organisms were grown in a nitrogen-free medium and in a medium containing nitrate nitrogen. The strains used differed widely in their ability to aid the host plant in symbiotic nitrogen fixation. They also differed somewhat in cultural characteristics

The Epitheliome: agent-based modelling of the social behaviour of cells

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

Common plants as indicators of habitat suitability for rare plants; quantifying the strength of the association between threatened plants and their neighbours

Rare plants are vulnerable to environmental change but easy to over-look during survey. Methods are therefore needed that can provide early warnings of population change and identify potentially suitable vegetation that could support new or previously overlooked populations. We developed an indicator species approach based on quantifying the association between rare plants across their British ecological range and their suite of more common neighbours. We combined quadrat data, targeted on six example species selected from the Botanical Society of Britain and Ireland's Threatened Plant Project (TPP), with representative survey data from across Britain. Bayes Theorem was then used to calculate the probability that the rare species would occur given the presence of an associated species that occurred at least once with the rare species in the TPP quadrats. These values can be interpreted as indicators of habitat suitability rather than expectations of species presence. Probability values for each neighbour species are calculated separately and are therefore unaffected by biased recording of other species. The method can still be applied if only a subset of species is recorded, for example, where weaker botanists record a pre-selected subset of more easily identifiable neighbour species. Disadvantages are that the method is constrained by the availability of quadrats currently targeted on rare species and results are influenced by any recording biases associated with existing quadrat data

Educating Future Environmental Health Professionals

Future environmental health problems will require a new generation of educated and trained professionals. Efforts to enhance the environmental public health workforce have been promoted by several organizations. While progress has been measured by these organizations, many environmental health academic programs are experiencing budget reductions and lower enrollments. One of the reasons for this trend is the so-called higher education crisis. We argue that training is not equivalent to education in the environmental health sciences, albeit the two terms are often used interchangeably. Organizations involved with the education, training, and credentialing of environmental health professionals must work together to ensure the viability and effectiveness of environmental health academic programs

Reimagining the milk supply chain: Reusable vessels for bulk delivery

Milk packaging has been analysed multiple times in pursuit of finding the most appropriate vessel from an environmental point of view. Research has concentrated on commercially available containers of 0.5 – 2.5 litres, usually made from High-Density Polyethylene (HDPE), Polyethylene Terephtalate (PET), paper-based cartons, or glass, with some studies considering a reuse scheme for glass bottles. Whilst applicable for household delivery, such a reuse scheme is not practical for delivery to cafés where large volumes of milk are used every day; little information is known about transportation of bulk volumes of milk in bigger vessels such as steel churns. This study compares a proposed milk supply chain using a mix of reusable stainless steel churns and reusable glass bottles with the current supply chain that uses single-use HDPE bottles, for transportation of milk to 10 cafés belonging to The University of Sheffield. A cradle-to-grave life cycle assessment (LCA) is conducted using data obtained from the university and Our Cow Molly, a local dairy farm which delivers milk to the university. Sensitivity analysis was performed around the recycling rate of plastic bottles, water consumption for churn cleaning, the reuse rate of glass bottles and churns and the source of the on-farm electricity. The study suggests that the greenhouse gas emission can be lowered by approx. 6.5 tons of CO2 equivalent annually if the reuse scheme is applied (this equates to a 65% reduction for the processes analysed). Considerable savings are also reported in categories such as water consumption, fossil resources depletion and cumulative energy demand. The reuse scheme is, however, likely to induce a similar or higher mineral resource use and higher environmental damage in the marine eutrophication category due to water treatment. Production of plastic bottles in the plastic scenario and maintenance and transport on the reusable side are the main contributors to the environmental impact. Further improvements in the reuse scenario could be achieved by reducing the amount of water used for cleaning and hence the electricity demand for water heating. The reuse scheme could also benefit environmentally from using an electric refrigerated van instead of a diesel vehicle

Precision Primordial 4^4He Measurement with CMB Experiments

Big bang nucleosynthesis (BBN) and the cosmic microwave background (CMB) are two major pillars of cosmology. Standard BBN accurately predicts the primordial light element abundances ($^4$He, D, $^3$He and $^7$Li), depending on one parameter, the baryon density. Light element observations are used as a baryometers. The CMB anisotropies also contain information about the content of the universe which allows an important consistency check on the Big Bang model. In addition CMB observations now have sufficient accuracy to not only determine the total baryon density, but also resolve its principal constituents, H and $^4$He. We present a global analysis of all recent CMB data, with special emphasis on the concordance with BBN theory and light element observations. We find $\Omega_{B}h^{2}=0.025+0.0019-0.0026$ and $Y_{p}=0.250+0.010-0.014$ (fraction of baryon mass as $^4$He) using CMB data alone, in agreement with $^4$He abundance observations. With this concordance established we show that the inclusion of BBN theory priors significantly reduces the volume of parameter space. In this case, we find $\Omega_{B}h^2=0.0244+0.00137-0.00284$ and $Y_p = 0.2493+0.0006-0.001$. We also find that the inclusion of deuterium abundance observations reduces the $Y_p$ and $\Omega_{B}h^2$ ranges by a factor of $\sim$2. Further light element observations and CMB anisotropy experiments will refine this concordance and sharpen BBN and the CMB as tools for precision cosmology.Comment: 7 pages, 3 color figures made minor changes to bring inline with journal versio

Orthorhombically Mixed s and dx2−y2_{x^2-y^2} Wave Superconductivity and Josephson Tunneling

The effect of orthorhombicity on Josephson tunneling in high T$_c$ superconductors such as YBCO is studied for both single crystals and highly twinned crystals. It is shown that experiments on highly twinned crystals experimentally determine the symmetry of the superconducting twin boundaries (which can be either even or odd with respect to a reflection in the twinning plane). Conversely, Josephson experiments on highly twinned crystals can not experimentally determine whether the superconductivity is predominantly $s$-wave or predominantly $d$-wave. The direct experimental determination of the order-parameter symmetry by Josephson tunneling in YBCO thus comes from the relatively few experiments which have been carried out on untwinned single crystals.Comment: 5 pages, RevTeX file, 1 figure available on request ([email protected]

Law, politics and the governance of English and Scottish joint-stock companies 1600-1850

This article examines the impact of law on corporate governance by means of a case study of joint-stock enterprise in England and Scotland before 1850. Based on a dataset of over 450 company constitutions together with qualitative information on governance practice, it finds little evidence to support the hypothesis that common-law regimes such as England were more supportive of economic growth than civil-law jurisdictions such as Scotland: indeed, levels of shareholder protection were slightly stronger in the civil-law zone. Other factors, such as local political institutions, played a bigger role in shaping organisational forms and business practice