Rule-based modelling of iron homeostasis in tuberculosis

To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and maintaining the required concentration of iron becomes a matter of contest between the host and the pathogen, both trying to achieve this through complex molecular networks. The extent of complexity makes it important to obtain a systems perspective of the interplay between the host and the pathogen with respect to iron homeostasis. We have reconstructed a systems model comprising 92 components and 85 protein-protein or protein-metabolite interactions, which have been captured as a set of 194 rules. Apart from the interactions, these rules also account for protein synthesis and decay, RBC circulation and bacterial production and death rates. We have used a rule-based modelling approach, Kappa, to simulate the system separately under infection and non-infection conditions. Various perturbations including knock-outs and dual perturbation were also carried out to monitor the behavioral change of important proteins and metabolites. From this, key components as well as the required controlling factors in the model that are critical for maintaining iron homeostasis were identified. The model is able to re-establish the importance of iron-dependent regulator (ideR) in Mtb and transferrin (Tf) in the host. Perturbations, where iron storage is increased, appear to enhance nutritional immunity and the analysis indicates how they can be harmful for the host. Instead, decreasing the rate of iron uptake by Tf may prove to be helpful. Simulation and perturbation studies help in identifying Tf as a possible drug target. Regulating the mycobactin (myB) concentration was also identified as a possible strategy to control bacterial growth. The simulations thus provide significant insight into iron homeostasis and also for identifying possible drug targets for tuberculosis.

Microscopic modelling of adsorption and the generalised surface layer hypothesis

Two- and three-state models for the adsorption of organic compounds at the electrode/electrolyte interface are proposed. Different size requirements, if any, for the neutral molecule and the adsorbing solvent are also considered. It is shown how the empirical, generalised surface layer (GSL) relationship (between the potential difference and the electrode charge) formulated by Damaskin et al. can be understood at the molecular level.

Recovery from DoS Attacks in MIPv6: Modelling and Validation

Denial-of-service (DoS) attacks form a very important category of security threats that are prevalent in MIPv6 (mobile internet protocol version 6) today. Many schemes have been proposed to alleviate such threats, including one of our own [9]. However, reasoning about the correctness of such protocols is not trivial. In addition, new solutions to mitigate attacks may need to be deployed in the network on a frequent basis as and when attacks are detected, as it is practically impossible to anticipate all attacks and provide solutions in advance. This makes it necessary to validate the solutions in a timely manner before deployment in the real network. However, threshold schemes needed in group protocols make analysis complex. Model checking threshold-based group protocols that employ cryptography have not been successful so far. Here, we propose a new simulation based approach for validation using a tool called FRAMOGR that supports executable specification of group protocols that use cryptography. FRAMOGR allows one to specify attackers and track probability distributions of values or paths. We believe that infrastructure such as FRAMOGR would be required in future for validating new group based threshold protocols that may be needed for making MIPv6 more robust.

Wavelet based spectral finite element modelling and detection of de-lamination in composite beams

In this paper, a model for composite beam with embedded de-lamination is developed using the wavelet based spectral finite element (WSFE) method particularly for damage detection using wave propagation analysis. The simulated responses are used as surrogate experimental results for the inverse problem of detection of damage using wavelet filtering. The WSFE technique is very similar to the fast fourier transform (FFT) based spectral finite element (FSFE) except that it uses compactly supported Daubechies scaling function approximation in time. Unlike FSFE formulation with periodicity assumption, the wavelet-based method allows imposition of initial values and thus is free from wrap around problems. This helps in analysis of finite length undamped structures, where the FSFE method fails to simulate accurate response. First, numerical experiments are performed to study the effect of de-lamination on the wave propagation characteristics. The responses are simulated for different de-lamination configurations for both broad-band and narrow-band excitations. Next, simulated responses are used for damage detection using wavelet analysis.

Modelling and classification of respiratory volume wavefourms

A technique is proposed for classifying respiratory volume waveforms(RVW) into normal and abnormal categories of respiratory pathways. The proposed method transforms the temporal sequence into frequency domain by using an orthogonal transform, namely discrete cosine transform (DCT) and the transformed signal is pole-zero modelled. A Bayes classifier using model pole angles as the feature vector performed satisfactorily when a limited number of RVWs recorded under deep and rapid (DR) manoeuvre are classified.

Quaternary association in beta-prism I fold plant lectins: Insights from X-ray crystallography, modelling and molecular dynamics

Dimeric banana lectin and calsepa, tetrameric artocarpin and octameric heltuba are mannose-specific beta-prism I fold lectins of nearly the same tertiary structure. MD simulations on individual subunits and the oligomers provide insights into the changes in the structure brought about in the protomers on oligomerization, including swapping of the N-terminal stretch in one instance. The regions that undergo changes also tend to exhibit dynamic flexibility during MD simulations. The internal symmetries of individual oligomers are substantially retained during the calculations. Energy minimization and simulations were also carried out on models using all possible oligomers by employing the four different protomers. The unique dimerization pattern observed in calsepa could be traced to unique substitutions in a peptide stretch involved in dimerization. The impossibility of a specific mode of oligomerization involving a particular protomer is often expressed in terms of unacceptable steric contacts or dissociation of the oligomer during simulations. The calculations also led to a rationale for the observation of a heltuba tetramer in solution although the lectin exists as an octamer in the crystal, in addition to providing insights into relations among evolution, oligomerization and ligand binding.