Time limits in the control of pollution systems

Exponentially growing pollution systems are examined from the point of view of control. A simplified mathematical model is used. Employing optimal control theory, we show that it is not always possible to drive the state (level of pollution) of such a system to a desired level. We prove that the state has to be smaller than certain bound for the system to be controllable. A specific example illustrates these ideas. The importance of this research lies in the fact that it shows the existence of certain state, and, consequently, time limits in the process of controlling the system.     

Synergistic control of oscillations in the NF-kappaB signalling pathway

In previous work, we studied the behaviour of a model of part of the NF-kappaB signalling pathway. The model displayed oscillations that varied both in number, amplitude and frequency when its parameters were varied. Sensitivity analysis showed that just nine of the 64 reaction parameters were mainly responsible for the control of the oscillations when these parameters were varied individually. However, the control of the properties of any complex system is distributed, and, as many of these reactions are highly non-linear, we expect that their interactions will be too. Pairwise modulation of these nine parameters gives a search space some 50 times smaller (81 against 4096) than that required for the pairwise modulation of all 64 reactions, and this permitted their study (which would otherwise have been effectively intractable). Strikingly synergistic effects were observed, in which the effect of one of the parameters was strongly (and even qualitatively) dependent on the values of another parameter. Regions of parameter space could be found in which the amplitude, but not the frequency (timing), of oscillations varied, and vice versa. Such modelling will permit the design and performance of experiments aimed at disentangling the role of the dynamics of oscillations, rather than simply their amplitude, in determining cell fate. Overall, the analyses reveal a level of complexity in these dynamic models that is not apparent from study of their individual parameters alone and point to the value of manipulating multiple elements of complex networks to achieve desired physiological effects.     

Adaptiveness of sex ratio control by the pupal parasitoid Itoplectis naranyae (Hymenoptera: Ichneumonidae) in response to host size

Adaptiveness of sex ratio control by the solitary parasitoid wasp Itoplectis naranyae (Hymenoptera: Ichneumonidae) in response to host size was studied, by examining whether differential effects of host size on the fitness of resulting wasps are to be found between males and females. The offspring sex ratio (male ratio) decreased with increasing host size. Larger hosts yielded larger wasps. Male larvae were less efficient in consuming larger hosts than female larvae. No significant interaction in development time was found between parasitoid sex and host size. Larger female wasps lived longer than smaller females, while longevity of male wasps did not increase with increasing wasp size. Smaller males were able to mate either with small or with large females, while larger males failed to mate with small females. Larger female wasps had a greater number of ovarioles and mature eggs at any one time than smaller females, although the number of eggs produced per host-feeding was not influenced by female wasps. Thus, the differential effect of host size on the fitness of males and females exists in I. naranyae. The basic assumption of the host-size model was therefore satisfied, demonstrating that sex ratio control by I. naranyae in response to host size is adaptive.     

Song-related brain regions in the red-winged blackbird are affected by sex and season but not repertoire size

Previous work in songbirds has delimited a neural system responsible for song production and control. Earlier studies have suggested that functional capacity in the song system may be related to the mass of the system in an animal's brain, and that adult plasticity in this neural system may be related to adult capacity for behavioral modification. We now test these hypotheses in adult red-winged blackbirds (Agelaius phoeniceus), a species in which song is produced primarily by males, new song types are added to the male's repertoire in adulthood, and there are substantial differences among males in song complexity. We find that the song system in males is much larger than in females. Song system nuclei become smaller in both sexes as the animals experience shorter days. We do not find any association between repertoire size and size of any of the song system structures examined. Thus, although sex differences in song may be related to differences between sexes in the mass of song system structures, individual differences in song do not appear to be directly related to mass within males. Seasonal change in song system structures in male redwings is consistent with there being a relation between adult plasticity in anatomy and in behavior; the large seasonal change in these structures in females suggests large seasonal changes in the function of these nuclei.     

Optimization of bioreactor using metabolic control analysis approach

A new methodology based on a metabolic control analysis (MCA) approach is developed for the optimization of continuous cascade bioreactor system. A general framework for representation of a cascade bioreactor system consisting of a large number of reactors as a single network is proposed. The kinetic and transport processes occurring in the system are represented as a reaction network with appropriate stoichiometry. Such representation of the bioreactor systems makes it amenable to the direct application of the MCA approach. The process sensitivity information is extracted using MCA methodology in the form of flux and concentration control coefficients. The process sensitivity information is shown to be a useful guide for determining the choice of decision variables for the purpose of optimization. A generalized problem of optimization of the bioreactor is formulated in which the decision variables are the operating conditions and kinetic parameters. The gradient of the objective function to be maximized with respect to all decision variables is obtained in the form of response coefficients. This gradient information can be used in any gradient-based optimization algorithm. The efficiency of the proposed technique is demonstrated with two examples taken from literature: biotransformation of crotonobetaine and alcohol fermentation in cascade bioreactor system.     

Machine Sharing in Manufacturing Systems: Total Flexibility versus Chaining

In this paper, we compare the operational performance of two machine-sharing configurations: total flexibility and chaining. We show that chaining captures most of the benefits of total flexibility while limiting the number of part types processed on any individual machine to only two. We examine the relative desirability of the two configurations under varying buffer sizes, loading conditions, number of machines, and setup times, as well as for different control policies. For nonzero setups times, we show that chained configurations can outperform fully flexible ones. This particularly is the case when either the number of machines or length of setup times is high. We also find that the effect of the system size on performance diminishes with the number of machines. This means that multiple smaller chains can perform almost as well as a single long one. Our results are consistent with the recent findings of Jordan and Graves (1995), who examined the economic benefits of chaining relative to full flexibility.     

Sex and seasonal differences in neurogenesis and volume of the song‐control system are associated with song in brood‐parasitic and non‐brood‐parasitic icterid songbirds

The song‐control system in the brain of songbirds is important for the production and acquisition of song and exhibits both remarkable seasonal plasticity and some of the largest neural sex differences observed in vertebrates. We measured sex and seasonal differences in two nuclei of the song‐control system of brood‐parasitic brown‐headed cowbirds (Molothrus ater) and closely‐related non‐parasitic red‐winged blackbirds (Agelaius phoeniceus). These species differ in both the development and function of song. Brown‐headed cowbirds have a larger sex difference in song than red‐winged blackbirds. Female cowbirds never sing, whereas female blackbirds do though much less than males. In cowbirds, song primarily functions in mate choice and males modify their song as they approach sexual maturity and interact with females. In red‐winged blackbirds, song is used primarily in territorial defence and is crystalized earlier in life. We found that the HVC was more likely to be discernable in breeding female blackbirds than in breeding female cowbirds. Compared to males, females had a smaller HVC and a smaller robust nucleus of the arcopallium (RA). However, females had higher doublecortin immunoreactivity (DCX+) in HVC, a measure of neurogenesis. Consistent with sex differences in song, the sex difference in RA volume was greater in cowbirds than in blackbirds. Males of both species had a smaller HVC with higher DCX+ in post‐breeding condition than in breeding condition when song is more plastic. Sex and seasonal differences in the song‐control system were closely related to variation in song in these two icterid songbirds. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1226–1240, 2016     

Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control

Partially-deleted mitochondrial DNA (ΔmtDNA) accumulates during aging of postmitotic tissues. This accumulation has been linked to decreased metabolic activity, increased reactive oxygen species formation and the aging process. Taking advantage of cell lines with heteroplasmic mtDNA mutations, we showed that, after severe mtDNA depletion, organelles are quickly and predominantly repopulated with ΔmtDNA, whereas repopulation with the wild-type counterpart is slower. This behavior was not observed for full-length genomes with pathogenic point mutations. The faster repopulation of smaller molecules was supported by metabolic labeling of mtDNA with [³H]thymidine during relaxed copy number control conditions. We also showed that hybrid cells containing two defective mtDNA haplotypes tend to retain the smaller one as they adjust their normal mtDNA copy number. Taken together, our results indicate that, under relaxed copy number control, ΔmtDNAs repopulate mitochondria more efficiently than full-length genomes.     

Combining control measures for more effective management of fisheries under uncertainty: quotas, effort limitation and protected areas

We consider combinations of three types of control measures for the management of fisheries when the input information for policy decisions is uncertain. The methods considered include effort controls, catch quotas and area closures. We simulated a hypothetical fishery loosely based on the Icelandic cod fishery, using a simple spatially explicit dynamic model. We compared the performance with respect to conserving the resource and economic return for each type of control measure alone and in combination. In general, combining more than one type of primary direct control on fishing provides a greater buffer to uncertainty than any single form of fishery control alone. Combining catch quota control with a large closed area is a most effective system for reducing the risk of stock collapse and maintaining both short and long-term economic performance. Effort controls can also be improved by adding closed areas to the management scheme. We recommend that multiple control methods be used wherever possible and that closed areas should be used to buffer uncertainty. To be effective, these closed areas must be large and exclude all principal gears to provide real protection from fishing mortality.     

Wheelchair-mounted integrated control systems for multiply handicapped people

Integrated control systems allow disabled people access to multiple functions from a single input device (for example a set of switches). Multiply handicapped users are thereby able to switch efficiently between wheelchair control, communication, computer access and control of their environment, without third-party help. Integrated systems have been developed for multiply handicapped children and adults in the Barnsley area. The design philosophy has concentrated upon utilizing, wherever possible, commercially available assistance devices and remotely controlling these via logic-based integrated control systems tailored to the needs and abilities of the individual client. This approach presents few problems as the inputs to commercially available devices are often based on simple switch control. The systems already supplied have proved, after an initial training period, to be easy to operate and have led to a considerable improvement in quality of life for the users. Computer-based, wheelchair-mounted integrated systems are now being developed. A prototype system currently emulates the logic-based controllers described above, employing the screen to display information on the current status of the system. Future development will move toward a more flexible system which will be able to read a variety of input signals and control a large number of outputs. The system will also have the facility to utilize software-based communications, keyboard emulation and environmental control packages as well as business and education software. Such a system could be easily set up, via software, for use by any disabled person.     

Stability and robustness of an organelle number control system: modeling and measuring homeostatic regulation of centriole abundance

Control of organelle abundance is a fundamental unsolved problem in cell biology. Mechanisms for number control have been proposed in which organelle assembly is actively increased or decreased to compensate for deviations from a set-point, but such phenomena have not been experimentally verified. In this report we examine the control of centriole copy number. We develop a simple scheme to represent organelle inheritance as a first-order Markov process and describe two figures of merit based on entropy and convergence times that can be used to evaluate performance of organelle number control systems. Using this approach we show that segregation of centrioles by the mitotic spindle can shape the specificity of the steady-state centriole number distribution but is neither necessary nor sufficient for stable restoration of centriole number following perturbations. We then present experimental evidence that living cells can restore correct centriole copy number following transient perturbation, revealing a homeostatic control system. We present evidence that correction occurs at the level of single cell divisions, does not require association of centrioles with the mitotic spindle, and involves modulation of centriole assembly as a function of centriole number during S-phase. Combining our experimental and modeling results, we identify two processes required for error correction, de novo assembly and number-limiting, and show that both processes contribute to robust and stable homeostatic control of centriole number, yielding a system capable of suppressing biological noise at the level of organelle abundance.     

'Slave' metabolites and enzymes. A rapid way of delineating metabolic control.

Although control of fluxes and concentrations tends to be distributed rather than confined to a single rate-limiting enzyme, the extent of control can differ widely between enzymes in a metabolic network. In some cases, there are enzymes that lack control completely. This paper identifies one surprising origin of such lack of control: If, in a metabolic system, there is a metabolite that affects the catalytic rate of only one enzyme, the corresponding enzyme cannot control any metabolic variable other than the concentration of that metabolite. We call such enzymes 'slave enzymes', and the corresponding metabolites 'slave metabolites'. Implications of the existence of slave enzymes for the control properties of enzymes further down the metabolic pathway are discussed and examined for the glycolytic pathway of yeast. Inadvertent assumptions in metabolic models may cause the latter incorrectly to calculate absence of metabolic control. The phenomenon of slave enzymes may well be important in enhancing metabolic signal transduction.     

Effect of linkage on the control of inbreeding in selection programmes

Selection and mating methods for controlling inbreeding in selection programmes are based on relationships obtained from pedigrees. The efficiency of these methods has always been tested by studies using genetic models of independent loci. However, under linkage the rate of inbreeding obtained from pedigrees can be different from the probability of identity by descent of genes. We simulated a quantitative trait under artificial selection controlled by a large number of genes spread on genome regions of different sizes. A method to control inbreeding based on minimising the average coancestry of selected individuals with a restriction in the loss of selection response, and a mating procedure to control inbreeding were applied. These methods, that use coancestry relationships, were not effective in controlling inbreeding when the genome sizes were smaller than five morgans or so. However, for larger genome sizes the methods were sufficiently efficient. For very tight linkage, methods that utilise molecular information from markers should be used. We finally discuss the effects of the selection of individual major genes on the neutral variability of adjacent genome regions.     

Adjusting phenotypes by noise control

Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.     

Pest control by genetic manipulation of sex ratio

We model the release of insects carrying an allele at multiple loci that shifts sex ratios in favor of males. We model two approaches to sex ratio alteration. In the first (denoted SD), meiotic segregation (or sperm fertility) is distorted in favor of gametes carrying the male-determining genetic element (e.g., Y-chromosome). It is assumed that any male carrying at least one copy of the SD allele produces only genotypically male offspring. In the second approach (denoted PM), the inserted allele alters sex ratio by causing genetically female individuals to become phenotypically male. It is assumed that any insect carrying at least one copy of the PM allele is phenotypically male. Both approaches reduce future population growth by reducing the number of phenotypic females. The models allow variation in the number of loci used in the release, the size of the release, and the negative fitness effect caused by insertion of each sex ratio altering allele. We show that such releases may be at least 2 orders of magnitude more effective than sterile male releases (SIT) in terms of numbers of surviving insects. For example, a single SD release with two released insects for every wild insect and a 5% fitness cost per inserted allele could reduce the target population to 1/1000th of the no-release population size, whereas a similar-sized SIT release would only reduce the population to one-fifth of its original size. We also compare these two sex ratio alteration approaches to a female-killing (FK) system and the sterile male technique when there are repeated releases over a number of generations. In these comparisons, the SD approach is the most efficient with equivalent pest suppression achieved by release of approximately 1 SD, 1.5-20 PM, 2-70 FK, and 16-3,000 SIT insects, depending on conditions. We also calculate the optimal number of SD and PM allele insertions to be used under various conditions, assuming that there is an additional genetic load incurred for each allelic insertion.     

On-line control of atracurium induced muscle relaxation

We described recently a microcomputer system capable of controlling muscle relaxation during surgical procedures; the system was tested and evaluated in 42 clinical trials involving the use of the muscle relaxant, d-tubucurarine. The advent of new non-depolarizing neuromuscular blocking drugs with significant clinical advantages makes it essential that any automatic control system for muscle relaxation can also be used with such drugs, and benefit from their improved properties. This paper describes a series of 22 clinical trials in which our controller was used successfully to control muscle relaxation using atracurium. We also investigated an alternative control strategy, taking advantage of the rapid elimination of atracurium from the body.     

A two-component model of host-parasitoid interactions: determination of the size of inundative releases of parasitoids in biological pest control

A two-component differential equation model is formulated for a host-parasitoid interaction. Transient dynamics and population crashes of this system are analysed using differential inequalities. Two different cases can be distinguished: either the intrinsic growth rate of the host population is smaller than the maximum growth rate of the parasitoid or vice versa. In the latter case, the initial ratio of parasitoids to hosts should exceed a given threshold, in order to (temporarily) halt the growth of the host population. When not only oviposition but also host-feeding occurs the dynamics do not change qualitatively. In the case that the maximum growth rate of the parasitoid population is smaller than the intrinsic growth rate of the host, a threshold still exists for the number of parasitoids in an inundative release in order to limit the growth of the host population. The size of an inundative release of parasitoids, which is necessary to keep the host population below a certain level, can be determined from the two-component model. When parameter values for hosts and parasitoids are known, an effective control of pests can be found. First it is determined whether the parasitoids are able to suppress their hosts fully. Moreover, using our simple rule of thumb it can be assessed whether suppression is also possible when the relative growth rate of the host population exceeds that of the parasitoid population. With a numerical investigation of our simple system the design of parasitoid release strategies for specific situations can be computed.     

Ecological role of control agent,and not just host‐specificity,determine risks of biological control

Biological control agents used to manage alien vegetation are generally viewed as providing an ecosystem service, owing to reduced ecological and economic costs of invasion following their release. In particular, gall‐formers are popular as biological control agents because they are host‐specific and therefore considered low risk. However, galls can also be considered to be ecological engineers, because they provide nutritional resources for native invertebrates. We tested whether native invertebrates had formed associations with the gall‐forming fungus Uromycladium tepperianum, introduced into South Africa to control the Australian invasive alien tree Acacia saligna, by collecting U. tepperianum galls and monitoring emergence. We found that a number of invertebrates had formed associations with the biological control agent, among which was the important citrus pest, Thaumatotibia leucotreta (false codling moth). We used pheromone‐baited traps to ascertain if this supplementary source of T. leucotreta increased their abundance in orchards close to patches of gall host, but did not find this to be the case. We did find, however, that control measures used by farmers explained T. leucotreta abundances in traps, which may have obscured detection of any effects of a nearby host for the pest. Nevertheless, this study illustrates the first case of a host‐specific classical biological control agent providing resources for an economically significant crop pest. We conclude that although biological control agents are strictly vetted to ensure host‐specificity, introduced biological control agents that become abundant and can act as ecological engineers pose risks when native biota form associations with them, resulting in a number of possible cascading ecosystem effects. In addition, there could be economic consequences when these associated species include agricultural pests. We conclude that not just host specificity, but potential ecological effects of biological control agents, should be considered in their selection.     

Robust control of initiation of prokaryotic chromosome replication: essential considerations for a minimal cell

A genomically and chemically detailed mathematical model of a "minimal cell" would be useful to understand better the "design logic" of cellular regulation. A "minimal cell" will be a prokaryote with the minimum number of genes necessary for growth and replication in an ideal environment (i.e., preformed precursors, constant temperature, etc.). The Cornell single-cell model of Escherichia coli serves as the basic framework upon which a minimal cell model can be constructed. A critical issue for any cell model is to describe a mechanism for control of initiation of chromosome replication. There is strong evidence that the essence of chromosome replication control is highly conserved in eubacteria and even extends to the archae. A generalized mechanism is possible based on binding of the protein DnaA-ATP to the origin of replication (oriC) as a primary control. Other features, such as regulatory inactivation of DnaA (RIDA) by conversion of DnaA-ATP to DnaA-ADP and titration of DnaA by binding to other DnaA boxes on the chromosome, have emerged as critical elements in obtaining a functional system to control initiation of chromosome synthesis. We describe a biologically realistic model of chromosome replication initiation control embedded in a complete whole-cell model that explicitly links the external environment to the mechanism of replication control. The base model is deterministic and then modified to include stochastic variation in the components for replication control. The stochastic model allows evaluation of the model's robustness, employing a low standard deviation of interinitiation time as a measure of robustness. Four factors were examined: DnaA synthesis rate; DnaA-ATP binding sites at oriC; the binding rate of DnaA-ATP to the nonfunctional DnaA boxes; and the effect of changing the number of nonfunctional binding sites. The observed DnaA synthesis rate (2000 molecules/cell) and the number of DnaA binding sites per origin (30) are close to the values predicted by the model to provide good control (low variance of interinitiation time), with a reasonable expenditure of cell resources. At relatively high binding rates for DnaA-ATP to the DnaA boxes (10(16) M(-1) s(-1)), increasing the number of DnaA binding sites to about 300, improved control (but little further improvement was seen by extension to 1000 boxes); however, at a low binding rate (10(10) M(-1) s(-1)), an increase in DnaA boxes had an adverse effect on control. The combination of all four factors is probably necessary to obtain a robust control system. Although this mechanism of replication initiation control is highly conserved, it is not clear if simpler control in a minimal cell might exist based on experimental observations with Mycoplasma. This issue is discussed in this investigation.