Block Search Stochastic Simulation Algorithm (BlSSSA): A Fast Stochastic Simulation Algorithm for Modeling Large Biochemical Networks.

Stochastic simulation algorithms are extensively used for exploring stochastic behavior of biochemical pathways/networks. Computational cost of these algorithms is high in simulating real biochemical systems due to their large size, complex structure and stiffness. In order to reduce the computational cost, several algorithms have been developed. It is observed that these algorithms are basically fast in simulating weakly coupled networks. In case of strongly coupled networks, they become slow as their computational cost become high in maintaining complex data structures. Here, we develop Block Search Stochastic Simulation Algorithm (BlSSSA). BlSSSA is not only fast in simulating weakly coupled networks but also fast in simulating strongly coupled and stiff networks. We compare its performance with other existing algorithms using two hypothetical networks, viz., linear chain and colloidal aggregation network, and three real biochemical networks, viz., B cell receptor signaling network, FceRI signaling network and a stiff 1,3-Butadiene Oxidation network. It has been shown that BlSSSA is faster than other algorithms considered in this study.

Photodynamic antimicrobial chemotherapy (PACT) using riboflavin inhibits the mono and dual species biofilm produced by antibiotic resistant Staphylococcus aureus and Escherichia coli.

PURPOSE: Multispecies biofilms play a significant role in persistent infections. Furthermore, by interspecies transfer of antibiotic resistance genes, multispecies biofilms spread antibiotic resistance. The purpose of this study was to investigate the effect of Photodynamic Antimicrobial Chemotherapy (PACT) using riboflavin on mono and multi species biofilms. METHODS: For this we used two clinically relevant opportunistic pathogens species E. coli and S. aureus as mono-species and multispecies biofilms. We did broth dilution assay for antibacterial, crystal violet assay for biofilms and fluorometric study for reactive oxygen species (ROS) and extracellular polymeric substance (EPS) production by phenol-HCl method. RESULTS: Antibacterial study revealed that photo-illuminated riboflavin shows bactericidal effect against each bacteria and their mix culture. E. coli was found to be little more resistant than S. aureus. Crystal violet assay revealed photo-illuminated riboflavin shows anti-biofilms activity against both mono and mix species biofilms. But mix species biofilms were more resistant to PACT than mono species biofilms. Further study revealed this may be due to the interaction between different EPS production, hence in mix species biofilms EPS production is less affected after PACT than mono species biofilms. We found photo-illuminated riboflavin increased the intracellular ROS production. CONCLUSION: Photo-illuminated riboflavin shows bactericidal and anti-biofilms effect against each bacteria and their mix culture. Photo-illuminated increased intracellular ROS production, which may induce the oxidative stress and destroy the respiratory system of bacteria.

Slow update stochastic simulation algorithms for modeling complex biochemical networks.

The stochastic simulation algorithm (SSA) based modeling is a well recognized approach to predict the stochastic behavior of biological networks. The stochastic simulation of large complex biochemical networks is a challenge as it takes a large amount of time for simulation due to high update cost. In order to reduce the propensity update cost, we proposed two algorithms: slow update exact stochastic simulation algorithm (SUESSA) and slow update exact sorting stochastic simulation algorithm (SUESSSA). We applied cache-based linear search (CBLS) in these two algorithms for improving the search operation for finding reactions to be executed. Data structure used for incorporating CBLS is very simple and the cost of maintaining this during propensity update operation is very low. Hence, time taken during propensity updates, for simulating strongly coupled networks, is very fast; which leads to reduction of total simulation time. SUESSA and SUESSSA are not only restricted to elementary reactions, they support higher order reactions too. We used linear chain model and colloidal aggregation model to perform a comparative analysis of the performances of our methods with the existing algorithms. We also compared the performances of our methods with the existing ones, for large biochemical networks including B cell receptor and FcϵRI signaling networks.

In Silico Modeling of Crabtree Effect.

BACKGROUND AND OBJECTIVE: Glycolytic activity during Crabtree effect is similar to that in tumor cells. Research regarding Crabtree effect is very much crucial. METHODS: The mechanism of metabolic activities in glycolysis pathway and oxidative phosphorylation pathway in regards to Crabtree effect in Saccharomyces cerevisiae was studied in this paper. We also explored the effects of hexose phosphates in the activities of respiratory chain complexes (III and IV) in inhibition of respiration. Besides, the enhancement of fermentation in response to excess glucose concentration was studied. We discussed the significance of Crabtree effect in mammalian cancer in terms of Crabtree effect in a Crabtree positive organism, as it is similar to cancer metabolism in mammalian cells. We developed an in silico model of Crabtree effect. RESULTS: A comparative study was performed with laboratory experiments regarding inhibitory role of fructose 1,6-bisphosphate on metabolic respiration. The model was simulated for different concentration levels of glucose and hexose phosphates using COPASI and SNOOPY tools. CONCLUSION: We have shown that a hike in glucose concentration increases ethanol concentration and leads glycolytic activity towards fermentation. This phenomenon occurs during Crabtree effect.

Near-field manipulation of spectroscopic selection rules on the nanoscale.

In conventional spectroscopy, transitions between electronic levels are governed by the electric dipole selection rule because electric quadrupole, magnetic dipole, and coupled electric dipole-magnetic dipole transitions are forbidden in a far field. We demonstrated that by using nanostructured electromagnetic fields, the selection rules of absorption spectroscopy could be fundamentally manipulated. We also show that forbidden transitions between discrete quantum levels in a semiconductor nanorod structure are allowed within the near-field of a noble metal nanoparticle. Atomistic simulations analyzed by an effective mass model reveal the breakdown of the dipolar selection rules where quadrupole and octupole transitions are allowed. Our demonstration could be generalized to the use of nanostructured near-fields for enhancing light-matter interactions that are typically weak or forbidden.

Janus nanostructures based on Au-TiO2 heterodimers and their photocatalytic activity in the oxidation of methanol.

Au-TiO2 snowman-like heterodimer nanoparticles were prepared by a surface sol-gel process based on gold Janus nanoparticles whose surface-protecting monolayers consisted of a hemisphere of hydrophobic 1-hexanethiolates and the other of hydrophilic 2-(2-mercaptoethoxy)ethanol. Transmission electron microscopic measurements showed that the resulting TiO2 nanoparticles (diameter 6 nm) exhibited well-defined lattice fringes that were consistent with the (101) diffraction planes of anatase TiO2. The heterodimer nanoparticles displayed apparent photoluminescence that was ascribed to electronic transitions involving trap states of TiO2 particles, and the photocatalytic activity was manifested by the oxidative conversion of methanol into formaldehyde, which was detected quantitatively by the Nash method. The enhanced photocatalytic performance, as compared to that of the TiO2 nanoparticles alone, was ascribed to the charge separation of photogenerated electrons and holes at the Au-TiO2 interface that was facilitated by the close proximity of the gold nanoparticles. These results suggested that (i) there were at least two possible pathways for photogenerated electrons at the TiO2 conduction band, decay to the trap states and transfer to the gold nanoparticles, and (ii) energy/electron transfer from the trap states to gold nanoparticles was less efficient. In essence, this study showed that the snowman-like heterodimers might be exploited as a homogeneous photocatalytic system for the preparation of functional molecules and materials.

Dithiocarbamate-capped silver nanoparticles.

Nanometer-sized silver particles were synthesized by using didecylamine dithiocarbamates as the protecting ligands. With control of the initial ligand-metal feed ratios, the core diameter of the resulting particles was found to vary from about 5 to 2.5 nm, as determined by transmission electron microscopic measurements. The core size dispersity was also found to decrease with increasing feed ratio. In UV-visible spectroscopic studies, the particle surface plasmon resonance peak diminished in intensity as the particle core size decreased, whereas in electrochemical measurements, smaller sized particles gave rise to well-defined quantized charging voltammetric features, in contrast to the featureless responses with the larger particles. Such single electron-transfer behaviors were consistent with those observed in STM measurements involving individual nanoparticles. Overall, this study provides an effective approach to the synthesis of stable nanometer-sized silver nanoparticles with interesting electronic and electrochemical properties.