Formal reasoning about synthetic biology using higher‐order‐logic theorem proving

Synthetic biology is an interdisciplinary field that uses well‐established engineering principles for performing the analysis of the biological systems, such as biological circuits, pathways, controllers and enzymes. Conventionally, the analysis of these biological systems is performed using paper‐and‐pencil proofs and computer simulation methods. However, these methods cannot ensure accurate results due to their inherent limitations. Higher‐order‐logic (HOL) theorem proving is proposed and used as a complementary approach for analysing linear biological systems, which is based on developing a mathematical model of the genetic circuits and the bio‐controllers used in synthetic biology based on HOL and analysing it using deductive reasoning in an interactive theorem prover. The involvement of the logic, mathematics and the deductive reasoning in this method ensures the accuracy of the analysis. It is proposed to model the continuous dynamics of the genetic circuits and their associated controllers using differential equations and perform their transfer function‐based analysis using the Laplace transform in a theorem prover. For illustration, the genetic circuits of activated and repressed expressions and autoactivation of protein, and phase lag and lead controllers, which are widely used in cancer‐cell identifiers and multi‐input receptors for precise disease detection, are formally analyzed.Inspec keywords: program verification, diseases, genetics, cancer, formal logic, theorem proving, formal verification, differential equations, proteins, transfer functions, inference mechanisms, Laplace transformsOther keywords: biological system, biological circuits, genetic circuits, associated controllers, computer simulation methods, higher‐order‐logic theorem proving, analysing linear biological systems, bio‐controllers, synthetic biology, deductive reasoning, reaction‐based models, transfer function based analysis, differential equation based models, phase lag, lead controllers, computer systems     

Extracellular biosynthesis of biocompatible CdSe quantum dots

An extracellular biosynthesis method has been developed to prepare cadmium selenide (CdSe) quantum dots (QDs) with strong fluorescence emission by incubating cheap Cd and Se inorganic salts with Escherichia coli (E.coli) bacteria. Ultraviolet–visible absorption spectra, photoluminescence (PL) spectra, and high‐resolution transmission electron microscopy analysis showed that the biosynthesised CdSe QDs have an average size of 3.1 nm, the excellent optical properties with fluorescence emission around 494 nm, and the good crystallinity. It was found that addition of 80 mg of mercaptosuccinic acid resulted in the formation of CdSe QDs with highest PL intensity. Furthermore, Fourier‐transform infrared spectra of as‐synthesised CdSe QDs confirmed the presence of a surface protein capping layer. The biosynthesised CdSe QDs were incorporated into the yeast cells as illustrated by laser confocal scanning microscopy images, showing a great potential in bio‐imaging and bio‐labelling application.Inspec keywords: microorganisms, molecular biophysics, fluorescence, visible spectra, nanofabrication, nanobiotechnology, proteins, cellular biophysics, nanostructured materials, wide band gap semiconductors, cadmium compounds, semiconductor quantum dots, II‐VI semiconductors, transmission electron microscopy, photoluminescence, optical microscopy, ultraviolet spectra, Fourier transform infrared spectra, biological techniques, semiconductor growthOther keywords: biocompatible CdSe quantum dots, extracellular biosynthesis method, cadmium selenide quantum dots, high‐resolution transmission electron microscopy analysis, biosynthesised CdSe QDs, Fourier‐transform infrared spectra, Escherichia coli, ultraviolet‐visible absorption spectra, PL intensity, fluorescence emission, photoluminescence spectra, optical properties, surface protein capping layer, laser confocal scanning microscopy images, bioimaging, biolabelling application, yeast cells, f mercaptosuccinic acid, CdSe     

Detecting small attractors of large Boolean networks by function‐reduction‐based strategy

Boolean networks (BNs) are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long‐term behaviour of systems. A central aim of Boolean‐network analysis is to find attractors that correspond to various cellular states, such as cell types or the stage of cell differentiation. This problem is NP‐hard and various algorithms have been used to tackle it with considerable success. The idea is that a singleton attractor corresponds to n consistent subsequences in the truth table. To find these subsequences, the authors gradually reduce the entire truth table of Boolean functions by extending a partial gene activity profile (GAP). Not only does this process delete inconsistent subsequences in truth tables, it also directly determines values for some nodes not extended, which means it can abandon the partial GAPs that cannot lead to an attractor as early as possible. The results of simulation show that the proposed algorithm can detect small attractors with length p = 4 in BNs of up to 200 nodes with average indegree K = 2.Inspec keywords: Boolean functions, genetics, cellular biophysicsOther keywords: detecting small attractors, function‐reduction‐based strategy, model gene regulatory networks, therapeutic intervention strategies, Boolean‐network analysis, cellular states, NP‐hard, singleton attractor, Boolean functions, partial gene activity profile, cell differentiation     

Cytotoxicity properties of functionalised carbon nanotubes on pathogenic bacteria

Nanobiotechnology is a promising field concerned with the using of engineered nanomaterials, which leads to the improvement of new human remedial against pathogenic bacteria modalities. In this work, silver nanoparticles (AgNPs) were prepared by an easy, cheap and low‐cost electro‐chemical method. The AgNPs were then loaded successfully on to multi‐walled carbon nanotubes (MWCNTs) using a modified chemical reaction process. The AgNPs on the MWCNTs were well spread and evenly distributed on the surfaces of the long nanotubes with well‐graphitised walls as examined by high‐resolution transmission electron microscopy. X‐ray diffraction and transmission electron microscopy were used for sample characterisation. Good dispersion of AgNPs was obtained on the surface of MWCNTs, resulting in an efficient reactivity of the carbon nanotubes surfaces. Finally, the antibacterial activity of AgNPs/MWCNTs hybrid was evaluated against two pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus exhibited excellent activity.Inspec keywords: nanocomposites, X‐ray diffraction, nanofabrication, nanoparticles, transmission electron microscopy, toxicology, silver, antibacterial activity, microorganisms, nanomedicine, multi‐wall carbon nanotubes, electrochemistryOther keywords: engineered nanomaterials, human remedial, pathogenic bacteria modalities, silver nanoparticles, multiwalled carbon nanotubes, modified chemical reaction process, well‐graphitised walls, high‐resolution transmission electron microscopy, cytotoxicity properties, functionalised carbon nanotubes, carbon nanotube surfaces, nanobiotechnology, low‐cost electrochemical method, AgNP‐MWCNT hybrid, X‐ray diffraction, antibacterial activity, Pseudomonas aeruginosa, Staphylococcus aureus, Ag‐C     

Algorithm to identify the optimal perturbation based on the net basin‐of‐state of perturbed states in Boolean network

Boolean networks are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long‐term behavior of systems. Here, the authors investigate the 1 bit perturbation, which falls under the category of structural intervention. The authors’ idea is that, if and only if a perturbed state evolves from a desirable attractor to an undesirable attractor or from an undesirable attractor to a desirable attractor, then the size of basin of attractor of a desirable attractor may decrease or increase. In this case, if the authors obtain the net BOS of the perturbed states, they can quickly obtain the optimal 1 bit perturbation by finding the maximum value of perturbation gain. Results from both synthetic and real biological networks show that the proposed algorithm is not only simpler and but also performs better than the previous basin‐of‐states (BOS)‐based algorithm by Hu et al..Inspec keywords: perturbation theory, genetics, Boolean functionsOther keywords: optimal perturbation, perturbed states, Boolean network, gene regulatory networks, basin‐of‐states‐based algorithm, state‐transition diagram, structural intervention, perturbation gain, synthetic biological networks, real biological networks, 1 bit perturbation     

M‐matrix‐based stability conditions for genetic regulatory networks with time‐varying delays and noise perturbations

Stability is essential for designing and controlling any dynamic systems. Recently, the stability of genetic regulatory networks has been widely studied by employing linear matrix inequality (LMI) approach, which results in checking the existence of feasible solutions to high‐dimensional LMIs. In the previous study, the authors present several stability conditions for genetic regulatory networks with time‐varying delays, based on M ‐matrix theory and using the non‐smooth Lyapunov function, which results in determining whether a low‐dimensional matrix is a non‐singular M ‐matrix. However, the previous approach cannot be applied to analyse the stability of genetic regulatory networks with noise perturbations. Here, the authors design a smooth Lyapunov function quadratic in state variables and employ M ‐matrix theory to derive new stability conditions for genetic regulatory networks with time‐varying delays. Theoretically, these conditions are less conservative than existing ones in some genetic regulatory networks. Then the results are extended to genetic regulatory networks with time‐varying delays and noise perturbations. For genetic regulatory networks with n genes and n proteins, the derived conditions are to check if an n × n matrix is a non‐singular M ‐matrix. To further present the new theories proposed in this study, three example regulatory networks are analysed.Inspec keywords: genetics, linear matrix inequalities, Lyapunov matrix equations, molecular biophysics, noise, proteinsOther keywords: M‐matrix‐based stability condition, genetic regulatory networks, time‐varying delays, noise perturbations, linear matrix inequality approach, high‐dimensional LMI, Lyapunov function, state variables, M‐matrix theory, proteins, nonsingular M‐matrix     

Small‐sized probe for local measuring electrical properties of the tissues inside of human body: design,modelling and simulation

In this study, a new idea is suggested for designing an appropriate bio‐impedance probe in the form of a biopsy forceps to measure the electrical properties of the tissues inside the body. First, by analytically solving the Laplace equation for wedge‐shaped tissue in the mouth of the probe, the relationship between electric potential (results from excitation current) in a different point on the tissue and the electrical properties of the tissue is obtained. Then, to evaluate the designed bio‐impedance probe using the finite element method and the experimental data obtained for different tissues by Gabriel et al., modelling and simulation at different frequencies from 50 Hz to 5 MHz were done. Finally, to evaluate the performance of the designed probe in comparison to other methods, measurements were carried out using three methods for the same tissue. Nyquist curves were drawn and electrical properties extracted for all the three methods. It was found that the designed probe results are close to the actual values with an error of <2%. The main features of the designed probe are small size and non‐invasive measurement.Inspec keywords: Laplace equations, biological tissues, finite element analysis, electric impedance measurement, bioelectric potentials, biomedical measurementOther keywords: noninvasive measurement, local measuring electrical properties, human body, wedge‐shaped tissue, electric potential, finite element method, bio‐impedance probe, small‐sized probe, biopsy forceps, excitation current, Nyquist curves, frequency 50.0 Hz to 5.0 MHz     

Properties of sparse penalties on inferring gene regulatory networks from time‐course gene expression data

Genes regulate each other and form a gene regulatory network (GRN) to realise biological functions. Elucidating GRN from experimental data remains a challenging problem in systems biology. Numerous techniques have been developed and sparse linear regression methods become a promising approach to infer accurate GRNs. However, most linear methods are either based on steady‐state gene expression data or their statistical properties are not analysed. Here, two sparse penalties, adaptive least absolute shrinkage and selection operator and smoothly clipped absolute deviation, are proposed to infer GRNs from time‐course gene expression data based on an auto‐regressive model and their Oracle properties are proved under mild conditions. The effectiveness of those methods is demonstrated by applications to in silico and real biological data.Inspec keywords: genetics, autoregressive processesOther keywords: sparse penalties, gene regulatory networks, time‐course gene expression data, GRN, biological functions, systems biology, sparse linear regression methods, steady‐state gene expression data, adaptive least absolute shrinkage, selection operator, smoothly clipped absolute deviation, autoregressive model, Oracle properties     

Bio‐green synthesis ZnO‐NPs in Brassica napus pollen extract: biosynthesis,antioxidant, cytotoxicity and pro‐apoptotic properties

The bio‐green methods of synthesis nanoparticles (NPs) have advantages over chemo‐physical procedures due to cost‐effective and ecofriendly products. The goal of current investigation is biosynthesis of zinc oxide NPs (ZnO‐NPs) and evaluation of their biological assessment. Water extract of Brassica napus pollen [rapeseed (RP)] prepared and used for the synthesis of ZnO‐NPs and synthesised ZnO‐NP characterised using ultraviolet–visible, X‐ray diffraction, Fourier‐transform infrared spectroscopy, field emission scanning electron microscope and transmission electron microscope. Antioxidant properties of ZnO‐NPs, cytotoxic and pro‐apoptotic potentials of NPs were also evaluated. The results showed that ZnO‐NPs have a hexagonal shape with 26 nm size. ZnO‐NPs synthesised in RP (RP/ZnO‐NPs) exhibited the good antioxidant potential compared with the butylated hydroxyanisole as a positive control. These NPs showed the cytotoxic effects against breast cancer cells (M.D. Anderson‐Metastasis Breast cancer (MDA‐MB)) with IC₅₀ about 1, 6 and 6 μg/ml after 24, 48 and 72 h of exposure, respectively. RP/ZnO‐NPs were found effective in increasing the expression of catalase enzyme, the enzyme involved in antioxidants properties of the cells. Bio‐green synthesised RP/ZnO‐NPs showed antioxidant and cytotoxic properties. The results of the present study support the advantages of using the bio‐green procedure for the synthesis of NPs as an antioxidant and as anti‐cancer agents.Inspec keywords: II‐VI semiconductors, wide band gap semiconductors, ultraviolet spectra, toxicology, X‐ray diffraction, biochemistry, zinc compounds, nanomedicine, enzymes, biomedical materials, particle size, antibacterial activity, transmission electron microscopy, molecular biophysics, visible spectra, nanofabrication, cellular biophysics, nanoparticles, cancer, field emission scanning electron microscopy, Fourier transform infrared spectra, semiconductor growthOther keywords: bio‐green synthesis ZnO‐NPs, zinc oxide NPs, synthesised ZnO‐NP, field emission scanning electron microscope, transmission electron microscope, antioxidant properties, bio‐green synthesised RP‐ZnO‐NPs, Fourier‐transform infrared spectroscopy, X‐ray diffraction, breast cancer cells MDA‐MB, pro‐apoptotic potentials, cytotoxic effects, catalase enzyme, bio‐green procedure, time 48.0 hour, time 72.0 hour, size 26.0 nm, time 24.0 hour, ZnO     

Multi‐scale approach for simulating time‐delay biochemical reaction systems

This study presents a multi‐scale approach for simulating time‐delay biochemical reaction systems when there are wide ranges of molecular numbers. The authors construct a new efficient approach based on partitioning into slow and fast subsets in conjunction with predictor–corrector methods. This multi‐scale approach is shown to be much more efficient than existing methods such as the delay stochastic simulation algorithm and the modified next reaction method. Numerical testing on several important problems in systems biology confirms the accuracy and computational efficiency of this approach.Inspec keywords: biochemistry, delays, biological techniques, predictor‐corrector methodsOther keywords: multiscale approach, time‐delay biochemical reaction systems, predictor–corrector methods, delay stochastic simulation algorithm, modified next reaction method, numerical testing, systems biology, method accuracy, computational efficiency     

Control of depth of anaesthesia using fractional‐order adaptive high‐gain controller

This study presents a fractional‐order adaptive high‐gain controller for control of depth of anaesthesia. To determine the depth of anaesthesia, the bispectral index (BIS) is utilised. To attain the desired BIS, the propofol infusion rate (as the control signal) should be appropriately adjusted. The effect of the propofol on the human body is modelled with the pharmacokinetic–pharmacodynamic (PK/PD) model. Physical properties of the patient such as gender, age, height and a like determine the parameters of the PK/PD model. This necessitates us to employ an appropriate adaptive controller. To attain this goal, a fractional‐order adaptive high‐gain controller is constructed to solve the tracking problem for minimum phase systems with relative degree two (such as the PK/PD model). This leads to a time‐varying gain adjusting according to a fractional‐order adaptation mechanism. Simulation results performed on various patients (considering the external disturbance and the measurement noise) show the effectiveness of the proposed method.Inspec keywords: medical control systems, gain control, adaptive control, closed loop systems, time‐varying systemsOther keywords: fractional‐order adaptive high‐gain controller, control signal, pharmacokinetic–pharmacodynamic model, fractional‐order adaptation mechanism, anaesthesia depth control, bispectral index, PK‐PD model, propofol infusion rate, tracking problem, minimum phase systems, time‐varying gain, BIS     

Wing‐kinematics measurement and flight modelling of the bamboo weevil C. buqueti

Insects are one of the most agile flyers in nature, and studying the kinematics of their wings can provide important data for the design of insect‐like wing‐flapping micro aerial vehicles. This study integrates high‐speed photogrammetry and three‐dimensional (3D) force measurement system to explore the kinematics of Cyrtotrachelus buqueti during the wing‐flapping flight. The tracking point at the wing tip of the hind wing was recorded using high‐speed videography. The lift‐thrust force characteristic of wing‐flapping motion was obtained by the 3D force sensor. Quantitative measurements of wing kinematics show that the wing‐flapping pattern of the hind wing of C. buqueti was revealed as a double figure‐eight trajectory. The kinematic modelling of the wing‐flapping pattern was then established by converting the flapping motion into rotational motion about the pivoting wing base in the reference coordinate system. Moreover, the lift force generated by C. buqueti during the wing‐flapping flight is sufficient to support its body weight without the need to use thrust force to compensate for the lack of lift force.Inspec keywords: video recording, force sensors, photogrammetry, kinematics, force measurement, aerospace componentsOther keywords: kinematic modelling, pivoting wing base, wing‐flapping flight, insect‐like wing‐flapping microaerial vehicles, high‐speed videography, 3D force sensor, Cyrtotrachelus buqueti, wing kinematics measurement, wing‐flapping motion pattern, lift‐thrust force characteristics, bamboo weevil C. buqueti, high‐speed photogrammetry, three‐dimensional force measurement system, 3D force measurement system, double figure‐eight trajectory     

Analytical study of biosynthesised silver nanoparticles against multi‐drug resistant biofilm‐forming pathogens

The emergence of the huge number of multi‐drug resistant (MDR) bacteria requires an alternative to the drugs. Silver nanoparticles (AgNPs) are a strong candidate for this due to their bactericidal properties, which can be better concluded by understanding their morphology and chemistry. The study hypothesised that AgNPs synthesised using leaves of Syzygium cumini can be used to treat locally emerging MDRs forming biofilms on indwelling medical devices. Synthesised particles were characterised by methods like UV–visible spectroscopy, X‐ray powder diffraction, scanning electron microscopy, transmission electron microscopy, and Zetasizer. Fourier transform infrared spectroscopy, and high‐performance liquid chromatography were used to predict phytochemicals present in the leaves. The shape of particles is revealed to be relatively spherical, with average size to be around 10–100 nm. Phenolic compounds are attributed to the formation of nanoparticles, stability analysis shows particles to be stable, and zeta potential determined the surface charge to be −20.1 mV. Biosynthesised particles are found to possess efficient antibacterial activity MDR bacteria developing biofilms in medical devices; hence, it is concluded that S. cumini based NPs can be used to develop a layer on implant‐related medical devices. Toxicity evaluation against A594 cancer cells portrays AgNPs to be potential tumour reduction agents in a concentration‐dependent manner.Inspec keywords: silver, visible spectra, X‐ray diffraction, transmission electron microscopy, scanning electron microscopy, chromatography, electrokinetic effects, cancer, biomedical materials, reduction (chemical), cellular biophysics, nanofabrication, nanoparticles, antibacterial activity, particle size, drugs, toxicology, nanomedicine, ultraviolet spectra, microorganisms, tumours, Fourier transform infrared spectraOther keywords: Syzygium cumini, biofilms, indwelling medical devices, UV‐visible spectroscopy, X‐ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, high‐performance liquid chromatography, biosynthesised particles, implant‐related medical devices, biosynthesised silver nanoparticles, multidrug resistant biofilm‐forming pathogens, multidrug resistant bacteria, MDR, bactericidal properties, morphology, scanning electron microscopy, s. cumini based NP, A594 cancer cells, tumour reduction, Ag     

Investigating conformational changes of Prefoldin β1 as result of applying external mechanical force without any position constraint

Manipulating molecular scale bio‐nanorobots and influencing their behaviour is one of the major challenges of new researches. Many coiled coil type proteins are involved in important biological functions due to physical properties that make them ideal for both nanoscale manipulation and sensing. The Prefoldin beta subunit from Thermococcus strain KS‐1(Prefoldin β1) is one of the possible proteins that can serve as a new bio‐nano‐actuator. Besides having a balanced architecture, Prefoldin β1 can exhibit a wide range of exclusive authorities. In this study, steered molecular dynamics simulation is applied along with the centre of mass pulling and analyses of Prefoldin β1 conformational changes to characterise some of those abilities. Thus, applying external mechanical force without any position constraint shows that it has no movement throughout simulations. This proposes a novel method to capture different sizes and shapes of cargoes. During simulations, each arm was found to be very flexible, allowing it to enlarge its central cavity and capture different cargoes. For a more accurate analysis, the variations in the cavity of nano‐actuator are investigated qualitatively and quantitatively with different parameters. Also, the force analysis of the arms can provide us with decent information about the performance of this nano‐actuator.Inspec keywords: nanobiotechnology, proteins, molecular biophysics, microrobots, molecular dynamics method, biological techniquesOther keywords: external mechanical force, coiled coil type proteins, nanoscale manipulation, Thermococcus strain KS‐1, steered molecular dynamics simulation, prefoldin beta subunit, bionanoactuator, prefoldin β1 conformational changes, molecular scale bionanorobots, centre‐of‐mass pulling     

Facile synthesis of multi‐walled carbon nanotube via folic acid grafted nanoparticle for precise delivery of doxorubicin

The motive of work was to develop a multi‐walled carbon nanoplatform through facile method for transportation of potential anticancer drug doxorubicin (DOX). Folic acid (FA)‐ethylene diamine (EDA) anchored and acid functionalised MWCNTs were covalently grafted with DOX via π–π stacking interaction. The resultant composite was corroborated by ¹ H NMR, FTIR, XRD, EDX, SEM, and DSC study. The drug entrapment efficiency of FA‐conjugated MWCNT was found high and stability study revealed its suitability in biological system. FA‐EDA‐MWCNTs‐DOX conjugate demonstrated a significant in vitro anticancer activity on human breast cancer MCF‐7 cells. MTT study revealed the lesser cytotoxicity of folate‐conjugated MWCNTs. The obtained results demonstrated the targeting specificity of FA‐conjugate via overexpressed folate receptor deemed greater scientific value to overcome multidrug protection during cancer therapy. The proposed strategy is a gentle contribution towards development of biocompatible targeted drug delivery and offers potential to address the current challenges in cancer therapy.Inspec keywords: toxicology, nanoparticles, biomedical materials, scanning electron microscopy, drug delivery systems, nanofabrication, nanomedicine, nanocomposites, cellular biophysics, cancer, drugs, multi‐wall carbon nanotubes, Fourier transform infrared spectra, X‐ray chemical analysis, differential scanning calorimetry, proton magnetic resonance, organic compoundsOther keywords: facile synthesis, multiwalled carbon nanotube, precise delivery, multiwalled carbon nanoplatform, drug entrapment efficiency, FA‐conjugated MWCNT, stability study, biological system, human breast cancer MCF‐7 cells, MTT study, folate‐conjugated MWCNTs, overexpressed folate receptor, cancer therapy, biocompatible targeted drug delivery, anticancer drug doxorubicin, π‐π stacking interaction, composite material, ¹ H NMR, in vitro anticancer activity, folic acid grafted nanoparticle, folic acid‐ethylene diamine, acid functionalised MWCNT, FTIR spectra, XRD, EDX, SEM, FA‐EDA‐MWCNT‐DOX conjugate, cytotoxicity, DSC, C     

First principle study of the self‐switching characteristics of the guanine based single optical molecular switch using carbon nanotube electrodes

The switching property of an optical single molecular switch based on a single DNA molecule guanine with a single walled carbon nanotube electrode has been investigated using density functional theory along with non‐equilibrium Green''s function based first principle approach. The semi‐empirical model of this single bio‐molecular switch has been operated at an ultra‐high 25 THz frequency in mid‐UV range. This single bio‐molecule comprises switching activity upon UV photo‐excitation. The influence of the highest occupied molecular orbital and lowest unoccupied molecular orbital gap and the quantum ballistic transmission into the switching activity are discussed in detail in this study. It has been observed that the maximum ON–OFF ratio, i.e. 327 is obtained at +0.8 V bias voltage. Theoretical results show that current through the twisted form is sufficiently larger than the straightened form, which recommends that this structure has smart prospective application in the future generation switching nanotechnology.Inspec keywords: molecular electronic states, density functional theory, ab initio calculations, DNA, organic compounds, molecular electronics, Green''s function methods, molecular biophysics, single‐wall carbon nanotubes, optical switches, orbital calculationsOther keywords: nonequilibrium Green''s function, semiempirical model, single bio‐molecular switch, UV photo‐excitation, lowest unoccupied molecular orbital gap, first principle study, single optical molecular switch, switching property, optical single molecular switch, single DNA molecule guanine, single walled carbon nanotube electrode, density functional theory, highest occupied molecular orbital gap, switching nanotechnology     

First principle approach towards logic design using hydrogen‐doped single‐strand DNA

Molecular logic gate has been proposed using single‐strand DNA (ssDNA) consisting of basic four nucleobases. In this study, density functional theory and non‐equilibrium Green''s function based first principle approach is applied to investigate the electronic transmission characteristics of ssDNA chain. The heavily hydrogen‐doped‐ssDNA (H‐ssDNA) chain is connected with gold electrode to achieve enhanced quantum‐ballistic transmission along 〈1 1 1〉 direction. Logic gates OR, Ex‐OR, NXOR have been implemented using this analytical model of H‐ssDNA device. Enhanced logic properties have been observed for ssDNA after H adsorption due to improved electronic transmission. Dense electron cloud is considered as logic ‘high’ (1) output in presence of hydrogen molecule and on the contrary sparse cloud indicate logic ‘low’ (0) in the absence of hydrogen molecule. Device current is significantly increased from 0.2 nA to 2.4 µA (approx.) when ssDNA chain is heavily doped with hydrogen molecule. The current–voltage characteristics confirm the formation of various Boolean logic gate operations.Inspec keywords: molecular electronics, Green''s function methods, hydrogen, logic gates, density functional theory, adsorption, DNA, logic design, logic circuitsOther keywords: hydrogen molecule, contrary sparse cloud, current–voltage characteristics, Boolean logic gate operations, first principle approach, logic design, hydrogen‐doped single‐strand DNA, molecular logic gate, density functional theory, electronic transmission characteristics, H, analytical model, NXOR logic gates, Ex‐OR logic gates, OR logic gates, hydrogen‐doped‐ssDNA chain, nonequilibrium Green''s function, nucleobases, dense electron cloud, improved electronic transmission, enhanced logic properties, H‐ssDNA device, enhanced quantum‐ballistic transmission, gold electrode     

Robust multi‐objective blood glucose control in Type‐1 diabetic patient

In this study, an automatic robust multi‐objective controller has been proposed for blood glucose (BG) regulation in Type‐1 Diabetic Mellitus (T1DM) patient through subcutaneous route. The main objective of this work is to control the BG level in T1DM patient in the presence of unannounced meal disturbances and other external noises with a minimum amount of insulin infusion rate. The multi‐objective output‐feedback controller with H_∞, H₂ and pole‐placement constraints has been designed using linear matrix inequality technique. The designed controller for subcutaneous insulin delivery was tested on in silico adult and adolescent subjects of UVa/Padova T1DM metabolic simulator. The experimental results show that the closed‐loop system tracks the reference BG level very well and does not show any hypoglycaemia effect even during the long gap of a meal at night both for in silico adults and adolescent. In the presence of 50 gm meal disturbance, average adult experience normoglycaemia 92% of the total simulation time and hypoglycaemia 0% of total simulation time. The robustness of the controller has been tested in the presence of irregular meals and insulin pump noise and error. The controller yielded robust performance with a lesser amount of insulin infusion rate than the other designed controllers reported earlier.Inspec keywords: robust control, patient treatment, diseases, closed loop systems, patient monitoring, biochemistry, medical control systems, blood, organic compoundsOther keywords: robust multiobjective blood glucose control, automatic robust multiobjective controller, blood glucose regulation, Type‐1 Diabetic Mellitus patient, BG level, T1DM patient, insulin infusion rate, multiobjective output‐feedback controller, pole‐placement constraints, linear matrix inequality technique, subcutaneous insulin delivery, total simulation time, insulin pump noise, adolescent subjects, meal disturbance, normoglycaemia 92, in silico adults, UVa‐Padova T1DM metabolic simulator, closed‐loop system, hypoglycaemia effect     

Overshoot in biological systems modelled by Markov chains: a non‐equilibrium dynamic phenomenon

A number of biological systems can be modelled by Markov chains. Recently, there has been an increasing concern about when biological systems modelled by Markov chains will perform a dynamic phenomenon called overshoot. In this study, the authors found that the steady‐state behaviour of the system will have a great effect on the occurrence of overshoot. They showed that overshoot in general cannot occur in systems that will finally approach an equilibrium steady state. They further classified overshoot into two types, named as simple overshoot and oscillating overshoot. They showed that except for extreme cases, oscillating overshoot will occur if the system is far from equilibrium. All these results clearly show that overshoot is a non‐equilibrium dynamic phenomenon with energy consumption. In addition, the main result in this study is validated with real experimental data.Inspec keywords: Markov processes, physiological modelsOther keywords: biological systems, Markov chains, nonequilibrium dynamic phenomenon, overshoot, steady‐state behaviour, oscillating overshoot, simple overshoot     

Bifurcation analysis of bistable and oscillatory dynamics in biological networks using the root‐locus method

Most of the biological systems including gene regulatory networks can be described well by ordinary differential equation models with rational non‐linearities. These models are derived either based on the reaction kinetics or by curve fitting to experimental data. This study demonstrates the applicability of the root‐locus‐based bifurcation analysis method for studying the complex dynamics of such models. The effectiveness of the bifurcation analysis in determining the exact parameter regions in each of which the system shows a certain dynamical behaviour, such as bistability, oscillation, and asymptotically equilibrium dynamics is shown by considering two mostly studied gene regulatory networks, namely Gardner''s genetic toggle switch and p53 gene network possessing two‐phase (mono‐stable/oscillation) dynamics.Inspec keywords: oscillations, curve fitting, differential equations, bifurcation, genetics, nonlinear dynamical systemsOther keywords: nonlinearities, reaction kinetics, root‐locus‐based bifurcation analysis method, complex dynamics, exact parameter regions, dynamical behaviour, equilibrium dynamics, studied gene regulatory networks, p53 gene network, bistable dynamics, oscillatory dynamics, biological networks, root‐locus method, biological systems, ordinary differential equation models