Dependence of bacterial growth rate on dynamic temperature changes

Temperature is an important determinant of bacterial growth. While the dependence of bacterial growth on different temperatures has been well studied for many bacterial species, prediction of bacterial growth rate for dynamic temperature changes is relatively unclear. Here, the authors address this issue using a combination of experimental measurements of the growth, at the resolution of 5 min, of Escherichia coli and mathematical models. They measure growth curves at different temperatures and estimate model parameters to predict bacterial growth profiles subject to dynamic temperature changes. They compared these predicted growth profiles for various step‐like temperature changes with experimental measurements using the coefficient of determination and mean square error and based on this comparison, ranked the different growth models, finding that the generalised logistic growth model gave the smallest error. They note that as the maximum specific growth increases the duration of this growth predominantly decreases. These results provide a basis to compute the dependence of the growth rate parameter in biomolecular circuits on dynamic temperatures and may be useful for designing biomolecular circuits that are robust to temperature.Inspec keywords: microorganisms, temperature, environmental factors, mean square error methods, parameter estimationOther keywords: bacterial growth rate, dynamic temperature changes, bacterial species, bacterial growth profiles, generalised logistic growth model, escherichia coli, model parameter estimation, coefficient of determination, mean square error, environmental conditions     

LSPR-Based Biosensing Enables the Detection of Antimicrobial Resistance Genes

The development of rapid, simple, and accurate bioassays for the detection of nucleic acids has received increasing demand in recent years. Here, localized surface plasmon resonance (LSPR) spectroscopy for the detection of an antimicrobial resistance gene, sulfhydryl variable β-lactamase (blaSHV), which confers resistance against a broad spectrum of β-lactam antibiotics is used. By performing limit of detection experiments, a 23 nucleotide (nt) long deoxyribonucleic acid (DNA) sequence down to 25 nm was detected, whereby the signal intensity is inversely correlated with sequence length (23, 43, 63, and 100 nt). In addition to endpoint measurements of hybridization events, the setup also allowed to monitor the hybridization events in real-time, and consequently enabled to extract kinetic parameters of the studied binding reaction. Performing LSPR measurements using single nucleotide polymorphism (SNP) variants of blaSHV revealed that these sequences can be distinguished from the fully complementary sequence. The possibility to distinguish such sequences is of utmost importance in clinical environments, as it allows to identify mutations essential for enzyme function and thus, is crucial for the correct treatment with antibiotics. Taken together, this system provides a robust, label-free, and cost-efficient analytical tool for the detection of nucleic acids and will enable the surveillance of antimicrobial resistance determinants.     

On vehicle placement to intercept moving targets

We address optimal placement of vehicles with simple motion to intercept a mobile target that is generated stochastically on a line segment. The optimality of vehicle placement is measured through a cost function associated with intercepting the target. With a single vehicle, we assume that the target moves (i) with fixed speed and in a fixed direction perpendicular to the line segment, or (ii) to maximize the distance from the line segment, or (iii) to maximize intercept time. In each case, we show that the cost function is strictly convex, its gradient is smooth, and the optimal vehicle placement is obtained by a standard gradient-based optimization technique. With multiple vehicles, we assume that the target moves with fixed speed and in a fixed direction perpendicular to the line segment. We present a discrete-time partitioning and gradient-based algorithm, and characterize conditions under which the algorithm asymptotically leads the vehicles to a set of critical configurations of the cost function.     

Robustness of a biomolecular oscillator to pulse perturbations

Biomolecular oscillators can function robustly in the presence of environmental perturbations, which can either be static or dynamic. While the effect of different circuit parameters and mechanisms on the robustness to steady perturbations has been investigated, the scenario for dynamic perturbations is relatively unclear. To address this, the authors use a benchmark three protein oscillator design – the repressilator – and investigate its robustness to pulse perturbations, computationally as well as use analytical tools of Floquet theory. They found that the metric provided by direct computations of the time it takes for the oscillator to settle after pulse perturbation is applied, correlates well with the metric provided by Floquet theory. They investigated the parametric dependence of the Floquet metric, finding that the parameters that increase the effective delay enhance robustness to pulse perturbation. They found that the structural changes such as increasing the number of proteins in a ring oscillator as well as adding positive feedback, both of which increase effective delay, facilitates such robustness. These results highlight such design principles, especially the role of delay, for designing an oscillator that is robust to pulse perturbation.Inspec keywords: proteins, oscillators, biomolecular electronics, biotechnologyOther keywords: biomolecular oscillator, environmental perturbations, circuit parameters, steady perturbations, dynamic perturbations, benchmark three protein oscillator design, Floquet theory, pulse perturbation, Floquet metric, ring oscillator, effective delay, repressilator, analytical tools, parametric dependence, positive feedback     

Transient response characteristics in a biomolecular integral controller

The cellular behaviour of perfect adaptation is achieved through the use of an integral control element in the underlying biomolecular circuit. It is generally unclear how integral action affects the important aspect of transient response in these biomolecular systems, especially in light of the fact that it typically deteriorates the transient response in engineering contexts. To address this issue, the authors investigated the transient response in a computational model of a simple biomolecular integral control system involved in bacterial signalling. They find that the transient response can actually speed up as the integral gain parameter increases. On further analysis, they find that the underlying dynamics are composed of slow and fast modes and the speed‐up of the transient response is because of the speed‐up of the slow‐mode dynamics. Finally, they note how an increase in the integral gain parameter also leads to a decrease in the amplitude of the transient response, consistent with the overall improvement in the transient response. These results should be useful in understanding the overall effect of integral action on system dynamics, particularly for biomolecular systems.Inspec keywords: transient response, molecular biophysics, cellular biophysics, microorganisms, biocontrolOther keywords: transient response characteristics, biomolecular integral controller, cellular behaviour, integral control element, biomolecular circuit, integral action, computational model, biomolecular integral control system, bacterial signalling, integral gain parameter     

Non‐normality can facilitate pulsing in biomolecular circuits

Non‐normality can underlie pulse dynamics in many engineering contexts. However, its role in pulses generated in biomolecular contexts is generally unclear. Here, the authors address this issue using the mathematical tools of linear algebra and systems theory on simple computational models of biomolecular circuits. They find that non‐normality is present in standard models of feedforward loops. They used a generalised framework and pseudospectrum analysis to identify non‐normality in larger biomolecular circuit models, finding that it correlates well with pulsing dynamics. Finally, they illustrate how these methods can be used to provide analytical support to numerical screens for pulsing dynamics as well as provide guidelines for design.Inspec keywords: linear algebra, feedforward, eigenvalues and eigenfunctions, network analysis, molecular biophysicsOther keywords: nonnormality, biomolecular circuits, pulse dynamics, engineering contexts, biomolecular contexts, linear algebra, systems theory, simple computational models, standard models, larger biomolecular circuit models     

Study of the potential of alternative crops by integration of multisource data using a neuro‐fuzzy technique

This work proposes a neuro‐fuzzy method for suggesting alternative crop production over a region using integrated data obtained from land‐survey maps as well as satellite imagery. The methodology proposed here uses an artificial neural network (multilayer perceptron, MLP) to predict alternative crop production. For each pixel, the MLP takes vector input comprising elevation, rainfall and goodness values of different existing crops. The first two components of the aforementioned input, that is, elevation and rainfall, are determined from contour information of land‐survey maps. The other components, such as goodness values of different existing crops, are based on the productivity estimates of soil determined by fuzzyfication and expert opinion (on soil) along with production quality by the Normalized Difference Vegetation Index (NDVI) obtained from satellite imagery. The methodology attempts to ensure that the suggested crop will also be a high productivity crop for that region.     

Magnetic plasmon formation and propagation in artificial aromatic molecules

The plasmonic properties of coupled metallic nanostructures are understood through the analogy between their collective plasmon modes and the electronic orbitals of corresponding molecules. Here we expand this analogy to planar arrangements of plasmonic nanostructures whose magnetic plasmons directly resemble the delocalized orbitals of aromatic hydrocarbon molecules. The heptamer structure serves as a benzene-like building block for a family of plasmonic artificial aromatic analogs with fused ring structures. Antiphase magnetic plasmons are excited in adjacent fused heptamer units, which for a linear multiheptamer structure is a behavior controlled by the number of units in the structure. This antiphase coupling gives rise to plasmonic "antiferromagnetic" behavior in multiple repeated heptamer structures, supporting the propagation of low-loss magnetic plasmons in this new waveguide geometry.     

Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS

Thirty-one histologically abnormal brains from patients with AIDS were studied in order to establish the relationship between multinucleated giant cells, viral protein expression, the various forms of human immunodeficiency virus type 1 (HIV-1) DNA, and clinical evidence of dementia. Unintegrated HIV-1 DNA of 2 to 8 kb was found in 22 of the 31 brains. Multinucleated giant cells without any other pathology were found in 14 cases; unintegrated 1-long terminal repeat (1-LTR) circular forms of HIV-1 DNA and strongly positive immunohistochemistry for gp41 and p24 were found in most of these brains. Most of these patients had a clinical diagnosis of HIV-1-associated dementia and cerebral atrophy. In all the other brains studied, 1-LTR circles were absent and immunohistochemistry for gp41 and p24 was usually negative. Very few of these patients had a clinical diagnosis of dementia. Sequence comparison of the LTR region from integrated HIV-1 DNA with that from unintegrated 1-LTR circular forms of HIV-1 DNA in 12 cases showed no significant differences. A further comparison of these brain-derived LTR sequences with LTR sequences derived directly from lymphoid tissue also showed strong sequence conservation. The V3 loop of the virus from the brain was sequenced in 6 cases and had a non-syncytium inducing-macrophage-tropic genotype. Our results show that (i) although unintegrated HIV-1 DNA was present in most brains from patients with AIDS, molecular evidence of high levels of viral replication was associated with the presence of multinucleated giant cells and dementia, and that (ii) the HIV-1 LTR is not a determinant of neurotropism. These observations suggest that replication of HIV-1 and not just the presence of HIV-1 DNA within giant cells makes the important contribution to central nervous system damage.