A network traffic flow model for motorway and urban highways

The research reported in this paper develops a network level traffic flow model (NTFM) which is applicable for both motorway and urban roads. It forecasts the traffic flow rates, queue propagation at the junctions and travel delays through the network. NTFM uses sub-models associated with all road and junction types which comprise the highway. The flow at any one part of the network is obviously very dependent upon the flows at all other parts of the network. To predict the two-way traffic flow in NTFM, an iterative simulation method is executed to generate the evolution of dependent traffic flows and queues. To demonstrate the capability of the model it is applied to a small case study network and a local Loughborough-Nottingham highway network. The results indicate that NTFM is capable of identifying the relationship between traffic flows and capturing traffic phenomena such as queue dynamics. By introducing a reduced flow rate on links of the network then the effects of strategies employed to carry out roadworks can be mimicked

Feedback control architecture and the bacterial chemotaxis network.

PMCID: PMC3088647This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Trade-off between Responsiveness and Noise Suppression in Biomolecular System Responses to Environmental Cues

When living systems detect changes in their external environment their response must be measured to balance the need to react appropriately with the need to remain stable, ignoring insignificant signals. Because this is a fundamental challenge of all biological systems that execute programs in response to stimuli, we developed a generalized time-frequency analysis (TFA) framework to systematically explore the dynamical properties of biomolecular networks. Using TFA, we focused on two well-characterized yeast gene regulatory networks responsive to carbon-source shifts and a mammalian innate immune regulatory network responsive to lipopolysaccharides (LPS). The networks are comprised of two different basic architectures. Dual positive and negative feedback loops make up the yeast galactose network; whereas overlapping positive and negative feed-forward loops are common to the yeast fatty-acid response network and the LPS-induced network of macrophages. TFA revealed remarkably distinct network behaviors in terms of trade-offs in responsiveness and noise suppression that are appropriately tuned to each biological response. The wild type galactose network was found to be highly responsive while the oleate network has greater noise suppression ability. The LPS network appeared more balanced, exhibiting less bias toward noise suppression or responsiveness. Exploration of the network parameter space exposed dramatic differences in system behaviors for each network. These studies highlight fundamental structural and dynamical principles that underlie each network, reveal constrained parameters of positive and negative feedback and feed-forward strengths that tune the networks appropriately for their respective biological roles, and demonstrate the general utility of the TFA approach for systems and synthetic biology

Characterization of Contaminants from a Sanitized Milk Processing Plant

Milk processing lines offer a wide variety of microenvironments where a diversity of microorganisms can proliferate. We sampled crevices and junctions where, due to deficient reach by typical sanitizing procedures, bacteria can survive and establish biofilms. The sampling sites were the holding cell, cold storage tank, pasteurizer and storage tank - transfer pump junction. The culturable bacteria that were isolated after the sanitation procedure were predominantly Pseudomonas spp., Serratia spp, Staphylococcus sciuri and Stenotrophomonas maltophilia. We assayed several phenotypic characteristics such as the ability to secrete enzymes and siderophores, as well as the capacity of the strains to form biofilms that might contribute to their survival in a mixed species environment. The Pseudomonas spp. isolates were found to either produce proteases or lecithinases at high levels. Interestingly, protease production showed an inverse correlation with siderophore production. Furthermore, all of the Serratia spp. isolates were strong biofilm formers and spoilage enzymes producers. The organisms identified were not mere contaminants, but also producers of proteins with the potential to lower the quality and shelf-life of milk. In addition, we found that a considerable number of the Serratia and Pseudomonas spp. isolated from the pasteurizer were capable of secreting compounds with antimicrobial properties

Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability

Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean1. These links are extensive, influencing a range of climate processes such as hurricane activity2 and African Sahel3, 4, 5 and Amazonian5 droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations6, 7, 8, 9, 10. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures11, 12, but climate models have so far failed to reproduce these interactions6, 9 and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860–2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910–1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol–cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol–cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions

IL-1α Mediated Chorioamnionitis Induces Depletion of FoxP3+ Cells and Ileal Inflammation in the Ovine Fetal Gut

Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum.Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1α at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days).3 and 7 d after IL-1α administration, intestinal mRNA levels for IL-4, IL-10, IFN-γ and TNF-α were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1.Intraamniotic IL-1α causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process

Characterization of the model for experimental testicular teratoma in 129/SvJ-mice

An animal model of experimental testicular teratoma has been established to study how a teratoma affects the host testis and how the host testis reacts against the teratoma. 129/SvJ-mice were used as experimental animals. To induce the experimental testicular teratoma, male gonadal ridges from 12-day-old 129/SvJ-mouse fetuses were grafted into the testes of adult mice for 1-12 weeks. The developing tumour was analysed by light and electron microscopy and by immunocytochemical localization of transcription factors SOX9 and c-kit, glial fibrillary acidic protein (GFAP) and type IV collagen. Testicular teratoma was observed in 36 out of 124 testes with implanted fetal gonadal ridges (frequency 29%). One spontaneous testicular teratoma was observed in this material from 70 male mice (1.5%). One week after implantation intracordal clusters of cells were seen in embryonic testicular cords of the graft as the first sign of testicular teratomas. Four weeks after implantation the embryonic testicular cords had totally disappeared from grafts with teratomas, and the tumour tissue had enlarged the testis and invaded the interstitium of the host testis. It consisted of solitary pieces of immature cartilage as well as of glial cells and of primitive neuroepithelium. Six to eight weeks after implantation the tumour tissue had expanded so that the enlarged testis could be detected by macroscopic enlargement of the scrotum. The testicular tissue of the host had practically disappeared, and only solitary disrupted seminiferous tubules of the host were seen surrounding the teratoma. Neuroepithelial structures of some teratomas cultured for 8 weeks had cells with a granular nucleus as a sign of obvious apoptosis. Eleven to 12 weeks after implantation the growth of the teratoma had stopped, and the histology corresponded to that of a mature cystic teratoma. GFAP, SOX9 and type IV collagen were strongly positive in some parts of the tumours cultured for 4 and 8 weeks, while only occasional c-kit-positive areas were observed in tumours cultured for 8 weeks. As conclusions: (1) the metastasizing capacity of the experimental testicular teratoma is very low during 12 weeks, but the behaviour of the tumour in the testicular tissue of the graft is invasive; (2) the growth of experimental testicular teratomas cease 6-8 weeks after implantation of the fetal gonadal ridges with the obvious apoptosis of the immature tissue components; (3) the model of experimental testicular teratoma in the mouse is suitable for studying how the teratoma affects the host testis and how the host testis reacts to teratoma