Optimization of biochemical systems by linear programming and general mass action model representations

A new method is proposed for the optimization of biochemical systems. The method, based on the separation of the stoichiometric and kinetic aspects of the system, follows the general approach used in the previously presented indirect optimization method (IOM) developed within biochemical systems theory. It is called GMA-IOM because it makes use of the generalized mass action (GMA) as the model system representation form. The GMA representation avoids flux aggregation and thus prevents possible stoichiometric errors. The optimization of a system is used to illustrate and compare the features, advantages and shortcomings of both versions of the IOM method as a general strategy for designing improved microbial strains of biotechnological interest. Special attention has been paid to practical problems for the actual implementation of the new proposed strategy, such as the total protein content of the engineered strain or the deviation from the original steady state and its influence on cell viability.     

Biochemical and thermodynamic analyses of energy conversion in extremophiles

A variety of extreme environments, characterized by extreme values of various physicochemical parameters (temperature, pressure, salinity, pH, and so on), are found on Earth. Organisms that favorably live in such extreme environments are called extremophiles. All living organisms, including extremophiles, must acquire energy to maintain cellular homeostasis, including extremophiles. For energy conversion in harsh environments, thermodynamically useful reactions and stable biomolecules are essential. In this review, I briefly summarize recent studies of extreme environments and extremophiles living in these environments and describe energy conversion processes in various extremophiles based on my previous research. Furthermore, I discuss the correlation between the biological system of electrotrophy, a third biological energy acquisition system, and the mechanism underlying microbiologically influenced corrosion. These insights into energy conversion in extremophiles may improve our understanding of the “limits of life”.

Abbreviations: PPi: pyrophosphate; PPase: pyrophosphatase; ITC: isothermal titration microcalorimetry; SVNTase: Shewanella violacea 5?-nucleotidase; SANTase: Shewanella amazonensis 5?-nucleotidase     

Analytical model of ion transport and conversion of light energy in chloroplasts

An analytical model, which describes the stationary transformation of light energy to the energy of pigment electronic excitation, has been constructed. A proton pump of the thylakoid membrane has been considered as a two-level conformon. The difference between the energies of the excited and ground states of both the pigment and the protein complex is assumed to be the energy of an absorbed photon. It has been found how the concentration of ions in a lumen and the potential across the thylakoid membrane depend on the concentration of ions in the stroma and the brightness temperature of absorbed radiation. Conditions for the maximum efficiency of the photosynthesis process have been analyzed. This model has been used to determine the electric potential (φ≈6.7 mV) at the chloroplast thylakoid membrane. The calculated value of the electric potential is in good agreement with the experimental data. A limitation on the stoichiometric coefficient of the proton transport through ATP-synthase, m>3, has been found theoretically.     

Dynamical analysis of periodic bursting in piece-wise linear planar neuron model

A piece-wise linear planar neuron model, namely, two-dimensional McKean model with periodic drive is investigated in this paper. Periodical bursting phenomenon can be observed in the numerical simulations. By assuming the formal solutions associated with different intervals of this non-autonomous system and introducing the generalized Jacobian matrix at the non-smooth boundaries, the bifurcation mechanism for the bursting solution induced by the slowly varying periodic drive is presented. It is shown that, the discontinuous Hopf bifurcation occurring at the non-smooth boundaries, i.e., the bifurcation taking place at the thresholds of the stimulation, leads the alternation between the rest state and spiking state. That is, different oscillation modes of this non-autonomous system convert periodically due to the non-smoothness of the vector field and the slow variation of the periodic drive as well.     

Stomatal regulation by microclimate and tree water relations: interpreting ecophysiological field data with a hydraulic plant model

Dynamics in microclimate and physiological plant traits were studied for Pubescent oak and Scots pine in a dry inner-alpine valley in Switzerland, at a 10 min resolution for three consecutive years (2001-2003). As expected, stomata tended to close with increasing drought in air and soil. However, stomatal aperture in oak was smaller than in pine under relatively wet conditions, but larger under dry conditions. To explore underlying mechanisms, a model was applied that (i) quantifies water relations within trees from physical principles (mechanistic part) and (ii) assumes that signals from light, stomatal aperture, crown water potential, and tree water deficit in storage pools control stomata (systemic part). The stomata of pine showed a more sensitive response to increasing drought because both factors, the slowly changing tree water deficit and the rapidly changing crown water potential, closed the stomata. By contrast, the stomata of oak became less drought-sensitive as the closing signal of crown water potential was opposed by the opening signal of tree water deficit. Moreover, parameter optimization suggests that oak withdrew more water from the storage pools and reduced leaf water potentials to lower levels, without risking serious damage by cavitation. The new model thus suggests how the hydraulic water flow and storage system determines the responses in stomatal aperture and transpiration to drought at time scales ranging from hours to multiple years, and why pine and oak might differ in such responses. These differences explain why oaks are more efficient competitors during drought periods, although this was not the case in the extremely dry year 2003, which provoked massive leaf loss and, from July onwards, physiological activity almost ceased.     

The role of behavior in evolution: a search for mechanism

Behavior has been viewed as a pacemaker of evolutionary change because changes in behavior are thought to expose organisms to novel selection pressures and result in rapid evolution of morphological, life history and physiological traits. However, the idea that behavior primarily drives evolutionary change has been challenged by an alternative view of behavior as an inhibitor of evolution. According to this view, a high level of behavioral plasticity shields organisms from strong directional selection by allowing individuals to exploit new resources or move to a less stressful environment. Here, I suggest that absence of clear mechanisms underlying these hypotheses impedes empirical evaluation of behavior’s role in evolution in two ways. First, both hypotheses focus on behavioral shifts as a key step in the evolutionary process but ignore the developmental mechanisms underlying these shifts and this has fostered unwarranted assumptions about the specific types of behavioral shifts that are important for evolutionary change. Second, neither hypothesis provides a means of connecting within-individual changes in behavior to population-level processes that lead to evolutionary diversification or stasis. To resolve these issues, I incorporate developmental and evolutionary mechanisms into a conceptual framework that generates predictions about the types of behavior and types of behavioral shifts that should affect both micro and macroevolutionary processes.     

Population dynamics of two rodent species in agro-ecosystems of central Argentina: intra-specific competition,land-use,and climate effects

Understanding the role of feedback structure (endogenous processes) and exogenous (climatic and environmental) factors in shaping the dynamics of natural populations is a central challenge within the field of population ecology. We attempted to explain the numerical fluctuations of two sympatric rodent species in agro-ecosystems of central Argentina using Royama’s theoretical framework for analyzing the dynamics of populations influenced by exogenous climatic forces. We found that both rodent species show a first-order negative feedback structure, suggesting that these populations are regulated by intra-specific competition (limited by food, space, or enemy-free space). In Akodon azarae endogenous structure seems to be very strongly influenced by human land-use represented by annual minimum normalized difference vegetation index (NDVI), with spring and summer rainfall having little influence upon carrying capacity. Calomys venustus’ population dynamics, on the other hand, seem to be more affected by local climate, also with spring and summer rainfall influencing the carrying capacity of the environment, but combined with spring mean temperature. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor

Summary Application of a single dose of a new type of proteinase inhibitor camostate (FOY-305) via orogastric tube was used in rats to study the dose-response relationship of resulting pancreatic stimulation. Doses up to 10 mg/ kg failed to elicit any response, while significant decrease in enzyme content and increase in serum CCK-levels were observed with doses ranging from 25 to 400 mg/kg. A single dose of 100 mg/kg was selected for a time-sequence analysis, which revealed a 60 to 70% depletion of enzyme stores persisting over 6 h and reverting to control levels by 12 h. Peak increases in serum CCK-levels (15-fold above the elevation observed after regular food intake) were found after 30 min and persisted as an 8-to 10-fold elevation for at least 3 h, then declined to control levels by 9 h. This prolonged endogenous hormone release and resulting pancreatic stimulation were also verified in a separate group of animals in which volume, protein, and enzyme output were measured after cannulation of the pancreatic duct. While volume secretion was not altered by feeding a single dose of 100 mg/kg FOY-305, protein and enzyme output increased 2-to 3-fold over a period of 7 h. Fine-structural analysis of the pancreas demonstrated efficient depletion of zymogen granules from acinar cells with all doses between 50 and 400 mg/kg, accompanied by the appearance of membrane material in the acinar lumina at 3 and 6 h. The same transient increase in the number of lysosomal bodies predominantly containing mitochondria with all doses above 50 mg/kg was interpreted as increased organelle turnover due to persisting hormonal stimulation.Supported by a grant from the Deutsche Forschungsgemeinschaft (Ke 113/15-1/2)     

Identification of Monogenea made easier: a new statistical procedure for an automatic selection of diagnostic linear measurements in closely related species

We introduce a new statistical method to select which morphological characters are most useful to identify monogenean species. The method estimates the average size overlap of candidate diagnostic structures among a set of species to individuate those that mostly differ between the species. To demonstrate our approach, we report a comprehensive analysis conducted on two of the most species‐rich monogenean genera: Dactylogyrus Diesing, 1850 and Gyrodactylus von Nordmann, 1832. We demonstrate that, in contrast to common taxonomic practice, very few but highly diagnostic measurements are necessary to correctly identify a specimen. In particular, we found that most of Dactylogyrus and Gyrodactylus species can be classified on the basis of the width of the supplementary connecting bar and of the length of the hook sickle, respectively.     

The interaction energy of charged filaments in an electrolyte: Results for all filament spacings

Recent studies have explored interactions between evolutionary game dynamics and population structure. Yet most studies so far mainly paid attention to unweighted and static networks. Here we explore evolutionary games played on dynamically weighted networks. Players update their strategies according to the payoffs they obtain. Players also update weights of their adjacent links depending on payoffs they gain through those links; profitable links are reinforced whereas unprofitable ones are weakened. The system is characterized by two time scales, the one for strategy update, β_S, and the other for weight adjustment, β_W. We find that, under a mean-field approximation, the asymptotic behavior of the system is described by the replicator equation with an effective payoff matrix, which is a combination of the original game matrix A and its transpose, A^T. Both analytical and numerical results show that such an adaptive weight adjustment mechanism dramatically promotes evolution of cooperation.     

Enhanced recombinant M-CSF production in CHO cells by glycerol addition: model and validation

Addition of stimulatory chemical such as glycerol was found to increase recombinant protein production in Chinese hamster ovary (CHO) cells. However, glycerol influenced cell mitosis and reduced cell growth rate. We developed a controlled proliferation strategy to utilize the stimulation of glycerol on recombinant protein production and mitigate the problem of growth inhibition. The approach is to apply a two-stage process, where cells are cultured without glycerol for a period of time in order to obtain enough cell density and then glycerol is added to achieve high specific productivity. In addition, a model for predicting the profiles of cell proliferation and recombinant protein production was developed and validated. A two-stage process, addition of 1% glycerol after 1 day of growth, could increase the final production of macrophage-colony stimulating factor (M-CSF) by 38% compared with the value obtained without addition of glycerol.     

Exacting predictions by cybernetic model confirmed experimentally: Steady state multiplicity in the chemostat

We demonstrate strong experimental support for the cybernetic model based on maximizing carbon uptake rate in describing the microorganism's regulatory behavior by verifying exacting predictions of steady state multiplicity in a chemostat. Experiments with a feed mixture of glucose and pyruvate show multiple steady state behavior as predicted by the cybernetic model. When multiplicity occurs at a dilution (growth) rate, it results in hysteretic behavior following switches in dilution rate from above and below. This phenomenon is caused by transient paths leading to different steady states through dynamic maximization of the carbon uptake rate. Thus steady state multiplicity is a manifestation of the nonlinearity arising from cybernetic mechanisms rather than of the nonlinear kinetics. The predicted metabolic multiplicity would extend to intracellular states such as enzyme levels and fluxes to be verified in future experiments. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012     

Regulation of human eye growth by the energy density of the radiation in the retina--a biophysical theory in ophthalmology

A number of theoretical and experimental models analyze regulation of eye growth in humans and animals. In this article we introduce a biophysical theory to explain human eye growth from an energetic point of view. We find different energy densities of the electromagnetic radiation in the retina for hyperopic, emmetropic and myopic eyes. We postulate a relation between the different energy densities of the radiation in the retina and growth regulation by the retina. Based on this relation between physics and biology we are modeling emmetropization, missing emmetropization in severe hyperopia and development and progression of myopia in correspondence with a number of clinical and experimental results.     

Cost and Efficiency of Large Mammal Census Techniques: Comparison of Methods for a Participatory Approach in a Communal Area, Zimbabwe

The comparison of precision is often advocated for the selection of an appropriate census and/or monitoring method for wildlife, but little attention is generally paid to their cost effectiveness, a crucial criterion given budgetary and logistical constraints. We present six direct count methods conducted in a communal area of the Zambezi Valley, Zimbabwe, and compare them in terms of (1) effort and cost to survey an area (sampling efficiency), and (2) efficiency in data collection (detection efficiency). Methods ranged from c.US$0.2 to over US$6.0/km² and needed from 0.1 to 5.0 human-h/km². The comparison of efficiencies showed the advantages of simple ground methods: foot counts and particularly bicycle counts appear well adapted to the ecological and human context of our study. The relative benefits and constraints of the different methods are discussed in the context of a community-based wildlife management programme.     

Dual-porosity model of solute diffusion in biological tissue modified by electroporation

In many electroporation applications mass transport in biological tissue is of primary concern. This paper presents a theoretical advancement in the field and gives some examples of model use in electroporation applications. The study focuses on post-treatment solute diffusion.     

Optimization of biodiesel supply chains based on small farmers: a case study in Brazil

This article presents a methodology for conceiving and planning the development of an optimized supply chain of a biodiesel plant sourced from family farms and taking into consideration agricultural, logistic, industrial, and social aspects. This model was successfully applied to the production chain of biodiesel fuel from castor oil in the semi-arid region of Brazil. Results suggest important insights related to the optimal configuration of the crushing units, regarding its location, technology, and when it should be available, as well as the configuration of the production zones along the planning horizon considered. Moreover, a sensitivity analysis is performed in order to measure how possible variations in the considered conjecture can affect the robustness of the solutions.     

Stratification by cyanobacteria in lakes: a dynamic buoyancy model indicates size limitations met by Planktothrix rubescens filaments

The ability of the Planktothrix rubescens to stratify in Lake Zürich is related to the size and shape of the cyanobacterial filaments. Detailed measurements made in the lake are used in a dynamic computer model of buoyancy regulation to investigate the vertical movements of filaments tracking the depth at which the irradiance would support neutral buoyancy. The movement of the filament lags behind the constantly changing target depth owing to (a) the time taken for the filament to respond to the irradiance by changing its density and (b) the time it takes to move by sinking down or floating up through the water column. The model simulates the stratification depth over a 5-month period of the summer from the continuous measurements of irradiance and weekly measurements of light attenuation and temperature, without any further adjustment over the period. Models using filaments of the size observed in Lake Zürich explain several details of the observed depth changes: smaller planktonic cyanobacteria (e.g. Limnothrix sp.) are unable to migrate fast enough and larger ones (e.g. Anabaena spp.) will overshoot and become entrained in the epilimnion. The model can be used to simulate recruitment of Planktothrix filaments from different depths after vernal stratification. Recruitment of filaments from depths down to 45 m will contribute to the metalimnetic population increase in early July.     

Optimization of economic policies and investment projects using a fuzzy logic based cost-effectiveness model of coral reef quality: empirical results for Montego Bay, Jamaica

 For effective mitigation of human impacts, quantitative models are required that facilitate a comprehensive analysis of the effects of human activity on reefs. Fuzzy logic procedures generate a complex dose-response surface that models the relationships among coral abundance and various inputs (e.g., physical damage, sedimentation, nutrient influx), within the context of the abiotic marine environment. This is linked to a nonlinear economic structure incorporating technical interventions (e.g., pollution treatment) and policy interventions (e.g., taxation) in eight economic sectors. Optimization provides insights into the most cost-effective means for protecting coral reefs under different reef quality targets. The research demonstrates that: (1) it is feasible to use fuzzy logic to model complex interactions in coral reef ecosystems; and, (2) conventional economic procedures for modeling cost-effectiveness can result in sub-optimal policy choices when applied to complex systems such as coral reefs. In Montego Bay, Jamaica, up to a 20% increase in coral abundance may be achievable through using appropriate policy measures having a present value cost of US$153 million over 25 years; a 10% increase is achievable at a cost of US$12 million. Accepted: 20 June 1999     

Photothermal beam deflection: a new method for in vivo measurements of thermal energy dissipation and photochemical energy conversion in intact leaves

A novel photosynthetic technique, photothermal deflection spectroscopy, is presented which is based on the mirage effect and allows the rapid measurement of thermal deactivation of excited pigments in leaf samples placed in an open cell. Modulated heat emission from leaves illuminated with intensity-modulated light was measured via the detection of the periodic deflection of a laser beam parallel to the sample surface. Photothermal deflection signals can be monitored in vivo in leaves placed in various, liquid or gaseous, environments with a satisfactory signal-to-noise ratio close to 60–80 (in distilled water) at low modulation frequencies (below 50 Hz). Using this new and simple photothermal method, it was possible to easily obtain useful information on the leaf photochemical activity and its light-saturation characteristics under normal or stress conditions, suggesting that in vivo deflection signals could be used for assaying the photosynthetic state of health of crop plants. The beam deflection method presented in this paper appears to be a potentially useful photosynthetic tool complementary to the related photoacoustic technique.Abbreviations DCMU dichlorophenyldimethylurea - PD photothermal deflection - PL photochemical energy storage - S/N ratio signal-to-noise ratio     

Environmental safety of biological control: Policy and practice in New Zealand

Introduction of biological control agents into New Zealand is regulated under the Hazardous Substances and New Organisms Act 1996 (HSNO). The legislation is strongly focused on the health and safety of people and the environment. HSNO is implemented by the Environmental Risk Management Authority, a quasi-judicial body of 6–8 people appointed by the Minister for the Environment. The process by which biological control applications are received and processed is described. Two case studies of weed biological control agents which have been through the HSNO process, and the scientific issues that arose in considering the environmental safety of these agents are discussed. The case studies presented are the applications to release the gall fly Procecidochares alani (Diptera: Tephritidae) to control mist flower Ageratina riparia, and three biological control agents, Macrolabis pilosellae (Diptera: Cecidomyiidae), Cheilosia urbana, and Cheilosia psilophthalma (Diptera: Syrphidae) for biological control of hawkweeds (Hieracium spp.). Both applications were approved for agent release into the environment.