Biotic Phase Research Articles

Lipid Metabolites as Potential Regulators of the Antibiotic Resistome in Tetramorium caespitum.

Antibiotic resistance genes (ARGs) are ancient but have become a modern critical threat to health. Gut microbiota, a dynamic reservoir for ARGs, transfer resistance between individuals. Surveillance of the antibiotic resistome in the gut during different host growth phases is critical to understanding the dynamics of the resistome in this ecosystem. Herein, we disentangled the ARG profiles and the dynamic mechanism of ARGs in the egg and adult phases of Tetramorium caespitum. Experimental results showed a remarkable difference in both gut microbiota and gut resistome with the development of T. caespitum. Meta-based metagenomic results of gut microbiota indicated the generalizability of gut antibiotic resistome dynamics during host development. By using Raman spectroscopy and metabolomics, the metabolic phenotype and metabolites indicated that the biotic phase significantly changed lipid metabolism as T. caespitum aged. Lipid metabolites were demonstrated as the main factor driving the enrichment of ARGs in T. caespitum. Cuminaldehyde, the antibacterial lipid metabolite that displayed a remarkable increase in the adult phase, was demonstrated to strongly induce ARG abundance. Our findings show that the gut resistome is host developmental stage-dependent and likely modulated by metabolites, offering novel insights into possible steps to reduce ARG dissemination in the soil food chain.

Intertwined synergistic abiotic and biotic degradation of polypropylene pellets in marine mesocosms

The accumulation of plastic waste in the oceans has caused growing concern for its effects on marine life. The interactions of plastics with environmental factors have been linked to fragmentation to micro- and nanoparticles with different properties and consequences, but the mechanism of fragmentation has not been fully understood yet. In this work, we investigate the combined effect of marine communities and ultraviolet (UV) radiation towards the degradation of virgin and artificially weathered polypropylene (PP) pellets after a long-term incubation period in marine mesocosms. The surface chemical alterations and deterioration of the polymer, in conjunction with the attachment and evolution of marine bacterial communities, the development of biofilm and exopolymeric substances (EPS), as well as the colloidal properties (zeta-potential and hydrodynamic diameter) of the mesocosms were studied. The surface area of both types of pellets decreased over time, despite no concrete weight change being observed. Cell growth, EPS production and colloid particle size were correlated to the loss of area. Therefore, we propose that surface area could be effectively monitored, instead of weight loss, as an alternative indicator of polymer degradation in biodegradation experiments. Changes in the chemical structure of the polymer, in addition to the evolution of the biological factors, implied that a complex degradation process alternated between two phases: an abiotic phase, when UV irradiation contributes to the deterioration of the polymer surface layers and a biotic phase, when marine communities degrade the weathered polymer surface to reveal the underlying layer of virgin polymer. Finally, microscopic particles, produced as a result of the decrease in pellet area, promoted the aggregation of colloidal particles. The role and impacts of these colloidal particles in marine ecosystems are yet as unidentified as that of micro- and nano-sized plastic particles and call for further investigation.

An analysis of organism lifelines in an industrial bioreactor using Lattice-Boltzmann CFD.

Euler-Lagrange CFD simulations, where the biotic phase is represented by computational particles (parcels), provide information on environmental gradients inside bioreactors from the microbial perspective. Such information is highly relevant for reactor scale-down and process optimization. One of the major challenges is the computational intensity of CFD simulations, especially when resolution of dynamics in the flowfield is required. Lattice-Boltzmann large-eddy simulations (LB-LES) form a very promising approach for simulating accurate, dynamic flowfields in stirred reactors, at strongly reduced computation times compared to finite volume approaches. In this work, the performance of LB-LES in resolving substrate gradients in large-scale bioreactors is explored, combined with the inclusion of a Lagrangian biotic phase to provide the microbial perspective. In addition, the hydrodynamic performance of the simulations is confirmed by verification of hydrodynamic characteristics (radial velocity, turbulent kinetic energy, energy dissipation) in the impeller discharge stream of a 29 cm diameter stirred tank. The results are compared with prior finite volume simulation results, both in terms of hydrodynamic and biokinetic observations, and time requirements.

Monitoring the Physiological State in the Dark Fermentation of Maize/Grass Silage Using Flow Cytometry and Electrooptic Polarizability Measurements

Dark fermentation (DF), a key biohydrogen-producing process, is generally operated as a black-box, by monitoring different operative macroscopic process parameters without evaluating or tracking the physiology of the biotic phase. The biotic phase in DF is constituted by a large variety of microorganisms, mainly fermentative bacteria. The present study uses two (electro)optical techniques, flow cytometry (FC) and frequency-dependent polarizability anisotropy (FDPA) measurements, to gain insights into the physiology of open mixed consortia throughout the DF process. The mixed consortia for DF were obtained from a methanogenic sludge, selecting spore-forming bacteria by means of an acid treatment. Then, DF systems with and without pH control were studied, using as substrate a mixture of maize and grass silage (9:1 w/w). Over the course of fermentation, the butyric pathway was dominant in both systems, and relevant titers of acetate, formate, and ethanol were detected; while hydrogen yields amounted to 20.80 ± 0.05 and 17.08 ± 0.05 NmL/gVS under pH-regulated and non-regulated conditions, respectively. The cytometric pattern analysis of the culture together with microscopic observations made it possible, over the course of fermentation, to identify and track the predominant morphologies in play (i.e., free spore, rod-shaped, and endospore, which are typical of Clostridium spp.). Furthermore, the use of the fluorescent dye DiBAC4(3) in FC and FDPA measurements provided similar information regarding the physiological state (PS) of the mixed consortia during the different phases of the culture.Graphical

Techno-Economic Assessment of Cell-Free Synthesis of Monoclonal Antibodies Using CHO Cell Extracts

Cell-free protein synthesis (CFPS) is an emerging tool for the rapid production of difficult-to-express proteins as well as for identifying protein synthesis bottlenecks. In CFPS, the biotic phase is substituted by extracts of living cells devoid of any of their own genetic material. The main advantage is that these systems delineate cell growth from recombinant protein production, enabling the expression of targets that would otherwise place too big a burden on living cells. We have conducted a techno-economic analysis of a CFPS system to produce monoclonal antibodies (mAbs) using extracts of Chinese hamster ovary (CHO) cells. We compare the performance of the CFPS system with two alternative production strategies: stable and transient gene expression in CHO cells. Our assessment shows that the viability of CFPS for mAb production requires a significant increase in the product yield and the recycling of high-cost components such as DNA. Nevertheless, CFPS shows significant promise for personalized medicine applications, providing a platform for on-demand production and simplified supply chains.

Adaptive-network-based Fuzzy Inference (anfis) Modelling of Particle Image Velocimetry (piv) Measurements in Stirred Tank Reactors

Mixing represents an energy-intensive unit operation which can significantly influence the performance of the different industrial processes. Efficient mixing is necessary to reduce spatial inhomogeneities within reactors and bioreactors. Particularly, in bioreactors, shear stress on microorganisms and physicochemical gradients might affect the physiological state of the biotic phase and, hence, decrease bioreaction yields.The present work presents an innovative machine-learning modelling approach which uses the adaptive-network-based fuzzy inference system (ANFIS) on experimentally velocity fields data collected through Particle Image Velocimetry (PIV) in STR under different operating conditions. The calibration and optimization of the ANFIS system are performed by dividing the PIV data into two subsets: training and validation data. Then, a sensitivity analysis is carried out varying the percentage of training data and certain features of the membership functions (number and type). The fitness of the produced models was scored by means of the fuzzy Goodness Index (GI), which combines the correlation coefficient (R2), index of agreement (IA) and relative root mean square error (RRMSE).

Discrimination of chemical and biological sulfide oxidation in a hybrid two-phase process

Hydrogen sulfide having the detrimental effect on humans and ecosystems can be metabolized by sulfur-oxidizing bacteria (SOB) as an energy source, however, SOB cannot tolerate high sulfide levels. A hybrid two-phase process was therefore proposed in this work to enhance the high-level sulfide oxidation based on discrimination of abiotic versus biotic oxidation. Separate experiments were performed to investigate the chemical and biological oxidations of sulfide at 500–2000 mg l−1. Products distribution showed that thiosulfate and intermediate products were the major products (more than 88%) of chemical oxidation, while sulfate was the predominant product in the biological oxidation. Nonetheless, sulfate formation declined from 90.5 to 35.5% with increasing sulfide level due to sulfide toxicity. To enhance oxidation, the effect of pH and adaptation methods were investigated, where insignificant changes were observed. The hybrid process resulted in complete sulfide transformation in the abiotic phase into less toxic products, which were further oxidized in biotic phase. This enhanced sulfate formation by 41% (55) at 1000 mg l−1 (2000) sulfide compared to the conventional biological case. The superiority of this hybrid two-phase process especially at higher sulfide levels was shown to be mainly due to complete sulfide detoxification.

Constrained global sensitivity analysis for bioprocess design space identification

The manufacture of protein-based therapeutics presents unique challenges due to limited control over the biotic phase. This typically gives rise to a wide range of protein structures of varying safety and in vivo efficacy. Herein we propose a computational methodology, enabled by the application of constrained Global Sensitivity Analysis, for efficiently exploring the operating range of process inputs in silico and identifying a design space that meets output constraints. The methodology was applied to an antibody-producing Chinese hamster ovary (CHO) cell culture system: we explored >8000 feeding strategies to identify a subset of manufacturing conditions that meet constraints on antibody titre and glycan distribution as an attribute of product quality. Our computational findings were then verified experimentally, confirming the applicability of this approach to a challenging production system. We envisage that this methodology can significantly expedite bioprocess development and increase operational flexibility.

A two-dimensional population balance model for cell growth including multiple uptake systems

Cell growth in a chemostat is a well-documented research topic. How cells uptake the available substrate to gain weight and engage cell division is not generally taken into account in the modelling bioreactors. In fact, the growth rate is related to a population doubling time whereas the microorganisms’ growth in mass is due to the mass transfer of substrates from the liquid phase to the biotic phase. Clearly, growth in mass precedes growth in number. Similarly, the transport of substrates down to the cell scale precedes the mass transfer. This article's main feature is a two-dimensional population balance model that allows to uncouple growth in mass and growth in number when the equilibrium between a cell population and its environment is disrupted. The cell length and the rate of anabolism are chosen as internal variables. It is proved that the hypothesis “growth in number=growth in mass” is valid at steady-state or in exponential growth only. The glucose uptake is assumed driven by two transport systems with a different affinity constant for the substrate. This combination of two regulated uptake systems operating in parallel explains a 3-fold increase in the uptake following a glucose pulse, but can also predict substrate uptake rates higher than the maximal batch value as observed in some experiments. These features are obtained by considering carbon fluxes in the formulation of regulation principles for uptake dynamics. The population balance's implementation in a multi-compartment reactor is a natural prospective work and allows extensions to industrial processes.

Biotic phase micropollutant distribution in horizontal sub-surface flow constructed wetlands

The distribution of micropollutants in biotic phases of horizontal sub-surface flow (HSSF) constructed wetlands was investigated. 88 diverse micropollutants (personal care products, pharmaceuticals and illicit drugs) were monitored for in full-scale HSSF steel slag and gravel beds to assess their fate and behaviour during tertiary wastewater treatment. Of the studied micropollutants 54 were found in receiving and treated wastewaters. Treatment reduced concentrations of several micropollutants by >50% (removal range −112% to 98%) and resulted in changes to the stereo-isomeric composition of chiral species. For example, stereo-selective changes were observed for 3,4-methylenedioxymethamphetamine (MDMA) and atenolol during HSSF constructed wetland treatment for the first time. Analysis of sludge present within the HSSF beds found 37 micropollutants to be present. However, concentrations for the majority of these micropollutants were not considered high enough to suggest partitioning into sludge was a contributing mechanism of removal. Nevertheless the preservative methylparaben was found at 2772mgbed−1. Its daily removal from wastewater of 3.4mgd−1 indicates partitioning and accumulation in sludge contributes to its removal. Other micropollutants found at high levels in sludge (relative to their overall removals) were the antidepressants sertraline and fluoxetine, and the metabolite desmethylcitalopram. Furthermore, process balances indicated uptake and metabolism by Phragmites australis (Cav.) Trin. ex Steud did not contribute significantly to micropollutant removal. However analysis of plant tissues evidenced uptake, metabolism and accumulation of recalcitrant micropollutants such as ketamine and carbamazepine. It is considered that the rate of uptake was too slow to have a notable impact on removal at the 14h hydraulic retention time. Despite evidence of other removal mechanisms at play (e.g., partitioning into sludge and plant uptake), findings indicate biodegradation is the dominant mechanism of micropollutant removal in HSSF constructed wetlands.

An organic bioactive pro-oxidant behavior in thermal degradation kinetics of polypropylene films

Due to its versatility and low cost, polypropylene (PP) is one of the most widely used polymers in the world. However, since it does not easily degrade in natural environment, various methods have been studied to reduce its lifetime. The pro-degrading additives promote the polymer degradation process by accelerating the polymer degradation under heat and/or UV. Eco-one is an organic bioactive pro-oxidant additive that induces biodegradation when it is incorporated into a polymeric matrix by attracting microorganisms in the biotic phase. The aim of this work was to investigate the abiotic degradability of this organic bioactive pro-oxidant additive in PP films. Thermal oxidation studies of the specimens were carried out to investigate the abiotic degradability. We analyzed compositions of PP films containing 1, 3, and 5% Eco-one by mass. These films were characterized by thermogravimetric analysis to calculate the activation energy (Eα) and to estimate their lifetime. Differential scanning calorimetry was conducted to provide oxidative induction time. The samples were then aged at 80 °C and characterized by Fourier transform infrared spectroscopy to obtain the carbonyl index (CI). Compositions containing 1% Eco-one additive showed the optimal composition with lower activation energy, and shorter predicted lifetime, suggesting easier thermal degradation. Furthermore, high CI was also observed in samples containing 1% additive, indicating thermodegradation for this composition.

Biotic interactions and community dynamics in the semiarid thorn scrub of Bosque Fray Jorge National Park, north-central Chile: A paradigm revisited

In 1989, we initiated a long-term field experiment in a semiarid thorn scrub community in north-central Chile. We posited that biotic interactions, particularly predation, interspecific competition, and herbivory assumed a primary top-down role in affecting small mammals and annual plants here. Using a multi-factorial design we selectively excluded vertebrate predators (principally carnivores and raptors) and a large small mammal herbivore, the degu (Octodon degus), from replicated 0.56 ha exclosures located in a valley near the coast in Bosque Fray Jorge National Park. Evidence initially supported effects of predator exclusion on O. degus but not for other small mammals in the assemblage (e.g., Phyllotis darwini, Abrothrix olivaceus). Subsequent years of monitoring have documented that predation has temporary effects on degu numbers, but that populations of this and other small mammals are much more strongly influenced by environmental bottom-up factors (i.e., rainfall). Further, our experimental manipulation has provided no evidence for negative interspecific competition effects on numbers of any small mammal in this assemblage. Degu exclusions, however, have had negative indirect effects on exotic annuals; native annuals appear to outcompete exotics especially during drought years The effect is magnified in all-small mammal exclusions. Since about 2002, selective exclusions of lagomorphs and small mammals have resulted in changes in cover of some perennial shrubs. Also notable has been a fundamental shift in the small mammal composition following the last major El Niño Southern Oscillation (ENSO) event in 2000–2002; degus now comprise a majority of small mammal biomass in the assemblage, and their numbers have become more stable and less temporally variable. This appears to have been caused by a shift in rainfall periodicity from strong interannual fluctuations in response to periodic ENSOs, to a more equitable pattern with more consistent annual rainfall. This represents one of the first documented cases of system-wide biotic phase shifts to a relatively modest change in rainfall regime. This may be indicative of ongoing climate change in the Chilean semiarid region, and we expect that further changes in the community will occur if those trends continue.

Influence of electrospun fiber mesh size on hMSC oxygen metabolism in 3D collagen matrices: Experimental and theoretical evidences

The traditional paradigm of tissue engineering of regenerating in vitro tissue or organs, through the combination of an artificial matrix and a cellular population has progressively changed direction. The most recent concept is the realization of a fully functional biohybrid, where both, the artificial and the biotic phase, concur in the formation of the novel organic matter. In this direction, interest is growing in approaches taking advantage of the control at micro- and nano-scale of cell material interaction based on the realization of elementary tassels of cells and materials which constitute the beginning point for the expansion of 3D more complex structures. Since a spontaneous assembly of all these components is expected, however, it becomes more fundamental than ever to define the features influencing cellular behavior, either they were material functional properties, or material architecture. In this work, it has been investigated the direct effect of electrospun fiber sizes on oxygen metabolism of h-MSC cells, when any other culture parameter was kept constant. To this aim, thin PCL electrospun membranes, with micro- and nano-scale texturing, were layered between two collagen slices up to create a sandwich structure (µC-PCL-C and nC-PCL-C). Cells were seeded on membranes, and the oxygen consumption was determined by a phosphorescence quenching technique. Results indicate a strong effect of the architecture of scaffolds on cell metabolism, also revealed by the increasing of HIF1-α gene expression in nC-PCL-C. These findings offer new insights into the role of materials in specific cell activities, also implying the existence of very interesting criteria for the control of tissue growth through the tuning of scaffold architecture.

A structured model for the simulation of bioreactors under transient conditions

AbstractModeling the transient behavior of continuous culture is of primary importance for the scale‐up of biological processes. Spatial heterogeneities increase with the reactor size and micro‐organisms have to cope with a fluctuating environment along their trajectories within the bioreactor. In this article, a structured model for bioreactions expressed in terms of biological extensive variables is proposed. A biological variable is introduced to calculate the growth rate of the population. The value is updated on the basis of the difference between the composition in the liquid and biotic phase. The structured model is able to predict the transient behavior of different continuous cultures subject to various drastic perturbations. This performance is obtained with a minimum increase in the standard unstructured model complexity (one additional time constant). In the final part, the consequences of decoupling the growth rate from the substrate uptake rate are discussed. © 2009 American Institute of Chemical Engineers AIChE J, 2009

Degradation of abiotically aged LDPE films containing pro-oxidant by bacterial consortium

The degradation of abiotically aged low density polyethylene (LDPE) films containing trace quantities of a representative pro-oxidant (cobalt stearate) was investigated in the presence of well defined enriched microbial strains namely, Bacillus pumilus, Bacillus halodenitrificans and Bacillus cereus in Basal salt medium. The films were initially subjected to an abiotic treatment comprising UV-B irradiation, and subsequently inoculated with the bacterial strains. The degradation in the polymeric chain was monitored by changes in the mechanical, morphological, structural and thermal properties. The abiotic treatment led to the formation of extractable oxygenated compounds as well as unoxidised low molecular weight hydrocarbons, which was confirmed by GC–MS studies. These were utilized by the bacterial consortium in the subsequent biotic phase and led to a mass loss of the polymer (8.4 ± 1.37%), which was also accompanied by an increase in the bacterial count. A decrease in the surface tension of the cell free medium was observed, which indicates that the bacterial consortium produced extracellular surface active molecules in order to enhance the bioavailability of the polymeric fixed carbon. The spectroscopic investigations reveal that the bacteria preferentially consume the oxygenated products leading to a decrease in the Carbonyl Index (CI), which in turn leads to an increase in the initial decomposition temperature as observed in the TGA traces. The morphological investigations reveal a biofilm formation on the surface, which was found to be scattered in certain regions and not uniform on the polymeric surface.

Distribution and fate of nonylphenol in an aquatic microcosm

An aquatic microcosm consisting of four compartments, namely surface microlayer (SM), water sediment and biota (zebra fish), was developed to investigate the distribution and fate of nonylphenol (NP) in an aquatic environment. Level III and level IV fugacity-based multimedia models were used to calculate the distribution and fate of NP. Data obtained from model calculations were in good agreement with those of the experiments. Results of the model calculations showed that 86.50% of all NP input was removed by advective outflow, while 61.99% of the remainder was distributed to the sediment phase, 34.89% to the water phase, 2.50×10 −2% to SM and 3.13% to the biotic phase. This finding demonstrates that sediment plays a key role in the fate of NP and acts as a sink in the aquatic environment. Bioconcentration factor (BCF) of NP in the zebra fish was high and varied in different parts of the fish. The highest BCF was 1440 in the viscera. After the uptake experiment, depuration of NP in clean water indicated that, the concentration of residue NP in the zebra fish was still high. This implies that NP in fish can pose a potential threat to human health due to its bioaccumulation in the food chain.

Gaseous Hexane Biodegradation by Fusarium solani in Two Liquid Phase Packed-Bed and Stirred-Tank Bioreactors

Biofiltration of hydrophobic volatile pollutants is intrinsically limited by poor transfer of the pollutants from the gaseous to the liquid biotic phase, where biodegradation occurs. This study was conducted to evaluate the potential of silicone oil for enhancing the transport and subsequent biodegradation of hexane by the fungus Fusarium solani in various bioreactor configurations. Silicone oil was first selected among various solvents for its biocompatibility, nonbiodegradability, and good partitioning properties toward hexane. In batch tests, the use of silicone oil improved hexane specific biodegradation by approximately 60%. Subsequent biodegradation experiments were conducted in stirred-tank (1.5 L) and packed-bed (2.5 L) bioreactors fed with a constant gaseous hexane load of 180 g x m(-3)(reactor) x h(-1) and operated for 12 and 40 days, respectively. In the stirred reactors, the maximum hexane elimination capacity (EC) increased from 50 g x m(-3)(reactor) x h(-1) (removal efficiency, RE of 28%) in the control not supplied with silicone oil to 120 g x m(-3)(reactor) x h(-1) in the biphasic system (67% RE). In the packed-bed bioreactors, the maximum EC ranged from 110 (50% RE) to 180 g x m(-3)(reactor) x h(-1) (> 90% RE) in the control and two-liquid-phase systems, respectively. These results represent, to the best of our knowledge, the first reported case of fungi use in a two-liquid-phase bioreactor and the highest hexane removal capacities so far reported in biofilters.

Mechanism of the Synergistic Toxicity of Malononitrile and p -Nitrobenzaldehyde with Photobacterium phosphoreum

In this study the mechanism of synergistic toxicity between malononitrile and p -nitrobenzaldehyde was revealed by examining their toxicodynamic and toxicokinetic interactions. The investigation of the toxicodynamic interactions focused on the interactions among malononitrile, p -nitrobenzaldehyde, and luciferase, and found that malononitrile does not induce luciferase to bind p -nitrobenzaldehyde. This result suggested that the synergistic toxicity does not arise from toxicodynamic interactions. Further research on toxicokinetic interactions compared the amounts of p -nitrobenzaldehyde being transported from the water phase to the biotic phase in two circumstances--in the presence of malononitrile and in its absence. The results of this research indicated that in the presence of malononitrile, more p -nitrobenzaldehyde is transported, and it is the increased amount of p -nitrobenzaldehyde that leads to the synergistic toxicity of malononitrile and p -nitrobenzaldehyde.

Cell cycle model to describe animal cell size variation and lag between cell number and biomass dynamics

The use of cell numbers rather than mass to quantify the size of the biotic phase in animal cell cultures causes several problems. First, the cell size varies with growth conditions, thus yields expressed in terms of cell numbers cannot be used in the normal mass balance sense. Second, experience from microbial systems shows that cell number dynamics lag behind biomass dynamics. This work demonstrates that this lag phenomenon also occurs in animal cell culture. Both the lag phenomenon and the variation in cell size are explained using a simple model of the cell cycle. The basis for the model is that onset of DNA synthesis requires accumulation of G1 cyclins to a prescribed level. This requirement is translated into a requirement for a cell to reach a critical size before commencement of DNA synthesis. A slower growing cell will spend more time in G1 before reaching the critical mass. In contrast, the period between onset of DNA synthesis and mitosis, tau(B), is fixed. The two parameters in the model, the critical size and tau(B), were determined from eight steady-state measurements of mean cell size in a continuous hybridoma culture. Using these parameters, it was possible to predict with reasonable accuracy the transient behavior in a separate shift-up culture, i.e., a culture where cells were transferred from a lean environment to a rich environment. The implications for analyzing experimental data for animal cell culture are discussed. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 372-379, 1997.

Complex growth dynamics in batch cultures: Experiments and cybernetic models

The cybernetic framework developed by Ramkrishna and co-workers is shown to encompass the regulation of nutrient transport processes as well as the effect of nutrient transport on the biotic phase. A structured model which accounts for both an abiotic or environmental phase and a biotic or cellular phase is proposed to describe bacterial growth on lactose as the limiting carbon and energy source. In the presence of lactose, competing uptake mechanisms are proposed. At low lactose concentrations, an energy-requiring transport process is the preferred uptake mechanism. The coupling between cellular energetics and nutrient uptake results in an interesting intermittent growth phenomenon. As the concentration of lactose increases, a nonenergetic transport process is preferred and cellular growth ceases to be intermittent. Model simulations are compared with previously reported experimental results and exhibit good agreement over the entire range of initial lactose concentrations.