189 research outputs found
Global stabilisation of continuous bioreactors: tools for analysis and design of feeding laws
[EN] This work revisits the dynamic behaviour of stirred continuous reactors in which a single bioreaction with unknown kinetics occurs. Conditions on the feeding strategy to avoid washing out the biomass and falling in batch operation are obtained. These conditions derive in a closed positively invariant region including the desired operating point. It is stated that no closed orbits may exist in this region and, furthermore, that no fixed point exists but on one of its borders. Therefore, global stability is achieved by finding a feeding law that fulfils the aforementioned invariant conditions and gives a single equilibrium for a first-order dynamics. These results are useful to determine the stability properties of different control laws and, more importantly, to design new ones. The main advantages of the proposed approach are its simplicity and that, differing from previous results, input saturation does not affect stability results. The potentiality of the developed tools is illustrated by means of classical and novel feeding laws. (C) 2017 Elsevier Ltd. All rights reserved.Financed by I216-2016 (UNLP), PICT2014-2394 (ANPCyT) and PIP112-2015-01-00837 (CONICET), Argentina; and by DPI2014-55276-C5-1-R MINECO/AEI/FEDER, UE. The material in this paper was not presented at any conference.De Battista, H.; Jamilis, M.; Garelli, F.; Picó, J. (2018). Global stabilisation of continuous bioreactors: tools for analysis and design of feeding laws. Automatica. 89:340-348. https://doi.org/10.1016/j.automatica.2017.12.041S3403488
Investigating microbial transformations of soil organic matter: synthesizing knowledge from disparate fields to guide new experimentation
Discerning why some soil organic matter (SOM) leaves soil profiles relatively quickly while other compounds, especially at depth, can be retained for decades to millennia is challenging for a multitude of reasons. Simultaneous with soil-specific advances, multiple other disciplines have enhanced their knowledge bases in ways potentially useful for future investigations of SOM decay. In this article, we highlight observations highly relevant for those investigating SOM decay and retention but often emanating from disparate fields and residing in literature seldom cited in SOM research. We focus on recent work in two key areas. First, we turn to experimental approaches using natural and artificial aquatic environments to investigate patterns of microbially mediated OM transformations as environmental conditions change, and highlight how aquatic microbial responses to environmental change can reveal processes likely important to OM decay and retention in soils. Second, we emphasize the importance of establishing intrinsic patterns of decay kinetics for purified substrates commonly found in soils to develop baseline rates. These decay kinetics – which represent the upper limit of the reaction rates – can then be compared to substrate decay kinetics observed in natural samples, which integrate intrinsic decay reaction rates and edaphic factors essential to the site under study but absent in purified systems. That comparison permits the site-specific factors to be parsed from the fundamental decay kinetics, an important advance in our understanding of SOM decay (and thus persistence) in natural systems. We then suggest ways in which empirical observations from aquatic systems and purified substrate–enzyme reaction kinetics can be used to advance recent theoretical efforts in SOM-focused research. Finally, we suggest how the observations in aquatic and purified substrate–enzyme systems could be used to help unravel the puzzles presented by oft-observed patterns of SOM characteristics with depth, as one example of the many perplexing SOM-related problems
Cryptic Population Dynamics: Rapid Evolution Masks Trophic Interactions
Trophic relationships, such as those between predator and prey or between pathogen and host, are key interactions linking species in ecological food webs. The structure of these links and their strengths have major consequences for the dynamics and stability of food webs. The existence and strength of particular trophic links has often been assessed using observational data on changes in species abundance through time. Here we show that very strong links can be completely missed by these kinds of analyses when changes in population abundance are accompanied by contemporaneous rapid evolution in the prey or host species. Experimental observations, in rotifer-alga and phage-bacteria chemostats, show that the predator or pathogen can exhibit large-amplitude cycles while the abundance of the prey or host remains essentially constant. We know that the species are tightly linked in these experimental microcosms, but without this knowledge, we would infer from observed patterns in abundance that the species are weakly or not at all linked. Mathematical modeling shows that this kind of cryptic dynamics occurs when there is rapid prey or host evolution for traits conferring defense against attack, and the cost of defense (in terms of tradeoffs with other fitness components) is low. Several predictions of the theory that we developed to explain the rotifer-alga experiments are confirmed in the phage-bacteria experiments, where bacterial evolution could be tracked. Modeling suggests that rapid evolution may also confound experimental approaches to measuring interaction strength, but it identifies certain experimental designs as being more robust against potential confounding by rapid evolution
Cryptic Population Dynamics: Rapid Evolution Masks Trophic Interactions
Trophic relationships, such as those between predator and prey or between pathogen and host, are key interactions linking species in ecological food webs. The structure of these links and their strengths have major consequences for the dynamics and stability of food webs. The existence and strength of particular trophic links has often been assessed using observational data on changes in species abundance through time. Here we show that very strong links can be completely missed by these kinds of analyses when changes in population abundance are accompanied by contemporaneous rapid evolution in the prey or host species. Experimental observations, in rotifer-alga and phage-bacteria chemostats, show that the predator or pathogen can exhibit large-amplitude cycles while the abundance of the prey or host remains essentially constant. We know that the species are tightly linked in these experimental microcosms, but without this knowledge, we would infer from observed patterns in abundance that the species are weakly or not at all linked. Mathematical modeling shows that this kind of cryptic dynamics occurs when there is rapid prey or host evolution for traits conferring defense against attack, and the cost of defense (in terms of tradeoffs with other fitness components) is low. Several predictions of the theory that we developed to explain the rotifer-alga experiments are confirmed in the phage-bacteria experiments, where bacterial evolution could be tracked. Modeling suggests that rapid evolution may also confound experimental approaches to measuring interaction strength, but it identifies certain experimental designs as being more robust against potential confounding by rapid evolution
Pyrimidine nucleotide de novo biosynthesis as a model of metabolic control
This manuscript presents a thorough investigation and description of metabolic control
dynamics in vivo and in silico using as a model de novo pyrimidine biosynthesis.
Metabolic networks have been studied intensely for decades, helping develop a detailed
understanding of the way cells carry out their biosynthetic and catabolic functions.
Biochemical reactions have been defined, pathway structures have been proposed,
networks of genetic control have been examined, and mechanisms of enzymatic activity
and regulation have been elucidated. In parallel with these types of traditional
biochemical analysis, there has been increasing interest in engineering cellular
metabolism for commercial and medical applications. Several different mathematical
approaches have been developed to model biochemical pathways by combining
stoichiometric and/or kinetic information with probabilistic analysis, or deciphering the
comparative logic of metabolic networks using genomic-derived data. However, most of
the research performed to date has relied on theoretical analyses and non-dynamic
physiological states. The studies described in this dissertation provide a unique effort
toward combining mathematical analysis with dynamic transition experimental data.
Most importantly these studies emphasize the significance of providing a quantitative framework for understanding metabolic control. The pathway of de novo biosynthesis of
pyrimidines in Escherichia coli provides an ideal model for the study of metabolic
control, as there is extensive documentation available on each gene and enzyme involved
as well as on their corresponding mechanisms of regulation. Biochemical flux through
the pathway was analyzed under dynamic conditions using middle-exponential growth
and steady state cultures. The fluctuations of the biochemical pathway intermediates and
end products transitions were quantified in response to physiological perturbation.
Different growth rates allowed the comparison of rapid versus long-term equilibrium
shifts in metabolic adaptation. Finally, monitoring enzymatic activity levels during
metabolic transitions provided insight into the interaction of genetic and biochemical
mechanisms of regulation. Thus, it was possible to construct a robust mathematical
model that faithfully represented, with a remarkable predictability, the nature of the
metabolic response to specific environmental perturbations. These studies constitute a
significant contribution to the fields of quantitative biochemistry and metabolic control,
which can be extended to other cellular processes as well as different organisms
McNair Scholars Journal
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Fermentation Development of Streptomyces thermonitrificans ISP5579
Conventional antibiotic fermentations are operated in the temperature range 25-3
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Mathematical and experimental approaches to the dimer catastrophe theory
Multicopy plasmids rely on random distribution for stable inheritance by daughter cells at division. Threats to plasmid copy number increase the probability of plasmid loss, which can be detrimental to both plasmid and host. Plasmid dimers emerge through homologous recombination. Dimers have two independent origins of replication and thus have a replicative advantage and reduced copy number. Models of plasmid behaviour suggest that dimers would overtake a cell population, but that this can be prevented if they impose a small metabolic load, which has been observed in vivo. Plasmid ColE1 also contains a cer site, which allows for dimer resolution by XerCD site-specific recombination. A small RNA, Rcd, is expressed from the cer site in dimers and interacts with tryptophanase to increase the concentration of indole in the cell. It is proposed that, as indole inhibits cell division, Rcd imposes a checkpoint on the cell until plasmid dimers are resolved.
In this work, plasmid behaviour in a growing cell population was modelled stochastically in more detail than previous work. A plasmid replication model suggested that dimers replicate to more than half the average copy number of monomers, perhaps accounting for their increased metabolic load. A cell population model suggested that the presence of dimer-only cells decreased the average plasmid stability by less than in previous models, which used a fixed plasmid copy number. The rate of dimer resolution required to affect plasmid stability was unreasonably high, indicating the necessity of the Rcd checkpoint. The model thus suggested that the checkpoint may be an escape route for dimer-only cells rather than an immediate response to the emergence of an initial dimer.
The Rcd checkpoint itself was also subject to critical analysis. It was realised that neither inhibition of cell division nor cell growth were sufficient to assist dimer resolution; inhibition of plasmid replication was required. Experiments in vivo found that indole inhibited plasmid replication at a concentration that may be achievable endogenously. DNA gyrase was investigated as a component of the mechanism of this inhibition, and indole was found to inhibit its supercoiling activity in vitro.The author of this work was the recipient of a PhD studentship from the Medical Research Council (UK
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