Enhancing Energy Storage Capacity of 3D Carbon Electrodes Using Soft Landing of Molecular Redox Mediators.

The incorporation of redox-active species into the electric double layer is a powerful strategy for enhancing the energy density of supercapacitors. Polyoxometalates (POM) are a class of stable, redox-active species with multielectron activity, which is often used to tailor the properties of electrochemical interfaces. Traditional synthetic methods often result in interfaces containing a mixture of POM anions, unreactive counter ions, and neutral species. This leads to degradation in electrochemical performance due to aggregation and increased interfacial resistance. Another significant challenge is achieving the uniform and stable anchoring of POM anions on substrates to ensure the long-term stability of the electrochemical interface. These challenges are addressed by developing a mass spectrometry-based subambient deposition strategy for the selective deposition of POM anions onto engineered 3D porous carbon electrodes. Furthermore, positively charged functional groups are introduced on the electrode surface for efficient trapping of POM anions. This approach enables the deposition of purified POM anions uniformly through the pores of the 3D porous carbon electrode, resulting in unprecedented increase in the energy storage capacity of the electrodes. The study highlights the critical role of well-defined electrochemical interfaces in energy storage applications and offers a powerful method to achieve this through selective ion deposition.

Structure and dynamics of dissociated and undissociated forms of nitric acid and their implications in interfacial mass transfer: insights from molecular dynamics simulations.

Nitric acid (HNO3) is widely used in various chemical and nuclear industries. Therefore, it is important to develop an understanding of the different forms of nitric acid for its practical applications. Molecular dynamics (MD) simulation is one of the best tools to investigate the behavior of concentrated nitric acid in aqueous solution with various forms together with pure nitric acid to identify a suitable model of nitric acid for use in simulations of biphasic systems for interfacial mass transfer. The Mulliken partial charge embedded OPLS-AA force field was used to model the neutral nitric acid, hydronium ion and nitrate ion, and it was found that the Mulliken partial charge embedded force field works quite well. The computed density of the dissociated and mixed-form acid was in good agreement with the experimental values. In water, the HNO3 molecule was seen to be coordinated with three water molecules in the first sphere of coordination. The distribution of water surrounding the HNO3 molecule and nitrate ion was corroborated by the DFT-optimized hydrated cluster. The calculated diffusivity values of the neutral acid and ions were significantly higher in the mixed form of nitric acid, which is an important dynamic quantity controlling the kinetics of the liquid-liquid interfacial extraction. The structural analysis revealed that the local aggregation is minimized when both forms of acid are present together in the solution. The water-ion and water-neutral acid interactions were predicted to be enhanced, as confirmed by H-bond studies. The shear viscosity of the mixed acid exhibited excellent agreement with the experimental values, which again confirms the consideration of the mixed form of nitric acid. The simulated value of surface tension for the mixed form of acid also appeared to be quite accurate based on the surface tension of water. The mixed form of nitric acid comprising both forms of acid is the best representation for nitric acid to be considered for MD simulations of biphasic systems. The mixed form of nitric acid established that the concentrated nitric acid may not be present either in the fully dissociated form or fully undissociated form in the solution.

Dipodal Silanes Greatly Stabilize Glass Surface Functionalization for DNA Microarray Synthesis and High-Throughput Biological Assays.

Glass is by far the most common substrate for biomolecular arrays, including high-throughput sequencing flow cells and microarrays. The native glass hydroxyl surface is modified by using silane chemistry to provide appropriate functional groups and reactivities for either in situ synthesis or surface immobilization of biologically or chemically synthesized biomolecules. These arrays, typically of oligonucleotides or peptides, are then subjected to long incubation times in warm aqueous buffers prior to fluorescence readout. Under these conditions, the siloxy bonds to the glass are susceptible to hydrolysis, resulting in significant loss of biomolecules and concomitant loss of signal from the assay. Here, we demonstrate that functionalization of glass surfaces with dipodal silanes results in greatly improved stability compared to equivalent functionalization with standard monopodal silanes. Using photolithographic in situ synthesis of DNA, we show that dipodal silanes are compatible with phosphoramidite chemistry and that hybridization performed on the resulting arrays provides greatly improved signal and signal-to-noise ratios compared with surfaces functionalized with monopodal silanes.

Inappropriately long post-ventricular atrial blanking leading to 'unnecessary' defibrillator discharge.

A 55-year-old lady with non-ischemic cardiomyopathy (NICM) was referred for multiple implantable cardioverter defibrillator (ICD) shocks. Stored electrograms (EGM) revealed atrial flutter (AFL) with A > V. Morphology match was good and RR-intervals were irregular. Despite all these, the dual-chamber-ICD (Abbott medical) classified this as ventricular tachycardia (VT-2) via V > A algorithm where it did not analyze morphology/stability and delivered therapy. Anti-tachycardia-pacing (ATP) was delivered which induced a true VT (rate in VF-zone) and immediate shock was delivered. It was hence appropriate but an 'unnecessary' shock. The offender was found to be an inappropriately programmed long post-ventricular atrial-blanking (PVAB) of 200 ms which led to undersensing of several atrial electrograms, falsely making V > A during a clear AFL.

Congenital right ventricular diverticulum: An atypical presentation.

Congenital ventricular diverticulum is a rare congenital malformation of the heart. It remains mostly asymptomatic unless associated with other congenital cardiac defects. We present a case of a 4-month-old child who had dextrocardia, large inlet ventricular septal defect, amounting to single ventricle, and severe pulmonary artery hypertension. There was a right ventricular diverticulum which passed through the foramina of Morgagni to give rise to a pulsating lump in the epigastrium. Right ventricular diverticulum presenting with a pulsating mass in the abdomen is a rare entity. The confirmation of diverticulum was made with histopathology.

Molecular Dynamics Simulation Studies on Structure, Dynamics, and Thermodynamics of Uranyl Nitrate Solution at Various Acid Concentrations.

The structural and dynamical characteristics of uranyl ions in an aqueous acidic environment are of immense importance in the field of nuclear fuel reprocessing. In view of that, the structural and dynamical behavior of the uranyl ion in water has been investigated by performing molecular dynamics (MD) simulations using different force fields. All the force fields have depicted similar structural and dynamical properties except the free energy of hydration where the Guilbaud-Wipff (GW) model performs well over the others. The calculated density using MD simulations is found to be in excellent agreement with the measured experimental density, which ensures the accuracy of the adopted GW force field. The calculated surface tension and shear viscosity are seen to be increased with uranyl nitrate concentrations. At a higher concentration of about 4.0 mol/L, the supersaturation effect has been captured by an inflection in the plot of surface tension and shear viscosity against concentration because of the solution heterogeneity, which was correlated by an inflection in the scattering intensity observed by performing the dynamic light scattering experiment. The binding mode of nitrate ions with the uranyl ion is found to be concentration-dependent, and at higher concentration, it is predominantly monodentate.

In silico prediction of ErbB signal activation from receptor expression profiles through a data analytics pipeline.

The ErbB signalling pathway has been studied extensively owing to its role in normal physiology and its dysregulation in cancer. Reverse engineering by mathematical models use the reductionist approach to characterize the network components. For an emergent, system-level view of the network, we propose a data analytics pipeline that can learn from the data generated by reverse engineering and use it to re-engineer the system with an agent-based approach. Data from a kinetic model that estimates the parameters by fitting to experiments on cell lines, were encoded into rules, for the interactions of the molecular species (agents) involved in biochemical reactions. The agent model, a digital representation of the cell line system, tracks the activation of ErbB1-3 receptors on binding with ligands, resulting in their dimerization, phosphorylation, trafficking and stimulation of downstream signalling through P13-Akt and Erk pathways. The analytics pipeline has been used to mechanistically link HER expression profile to receptor dimerization and activation of downstream signalling pathways. When applied to drug studies, the efficacy of a drug can be investigated in silico. The anti-tumour activity of Pertuzumab, a monoclonal antibody that inhibits HER2 dimerization, was simulated by blocking 80% of the cellular HER2 available, to observe the effect on signal activation.

Molecular dynamics simulation for the test of calibrated OPLS-AA force field for binary liquid mixture of tri-iso-amyl phosphate and n-dodecane.

Tri-isoamyl phosphate (TiAP) has been proposed to be an alternative for tri-butyl phosphate (TBP) in the Plutonium Uranium Extraction (PUREX) process. Recently, we have successfully calibrated and tested all-atom optimized potentials for liquid simulations using Mulliken partial charges for pure TiAP, TBP, and dodecane by performing molecular dynamics (MD) simulation. It is of immense importance to extend this potential for the various molecular properties of TiAP and TiAP/n-dodecane binary mixtures using MD simulation. Earlier, efforts were devoted to find out a suitable force field which can explain both structural and dynamical properties by empirical parameterization. Therefore, the present MD study reports the structural, dynamical, and thermodynamical properties with different mole fractions of TiAP-dodecane mixtures at the entire range of mole fraction of 0-1 employing our calibrated Mulliken embedded optimized potentials for liquid simulation (OPLS) force field. The calculated electric dipole moment of TiAP was seen to be almost unaffected by the TiAP concentration in the dodecane diluent. The calculated liquid densities of the TiAP-dodecane mixture are in good agreement with the experimental data. The mixture densities at different temperatures are also studied which was found to be reduced with temperature as expected. The plot of diffusivities for TiAP and dodecane against mole fraction in the binary mixture intersects at a composition in the range of 25%-30% of TiAP in dodecane, which is very much closer to the TBP/n-dodecane composition used in the PUREX process. The excess volume of mixing was found to be positive for the entire range of mole fraction and the excess enthalpy of mixing was shown to be endothermic for the TBP/n-dodecane mixture as well as TiAP/n-dodecane mixture as reported experimentally. The spatial pair correlation functions are evaluated between TiAP-TiAP and TiAP-dodecane molecules. Further, shear viscosity has been computed by performing the non-equilibrium molecular dynamics employing the periodic perturbation method. The calculated shear viscosity of the binary mixture is found to be in excellent agreement with the experimental values. The use of the newly calibrated OPLS force field embedding Mulliken charges is shown to be equally reliable in predicting the structural and dynamical properties for the mixture without incorporating any arbitrary scaling in the force field or Lennard-Jones parameters. Further, the present MD simulation results demonstrate that the Stokes-Einstein relation breaks down at the molecular level. The present methodology might be adopted to evaluate the liquid state properties of an aqueous-organic biphasic system, which is of great significance in the interfacial science and technology.

Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology.

Motivation: Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments. Results: A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies. Availability and Implementation: Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material . Contact: liz.csir@gmail.com. Supplementary information: Supplementary data are available at Bioinformatics online.

In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-ethyl-trans-stilbene (DETS) Isolated from Bacillus cereus as a Potent Candidate against Malignant Melanoma.

3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 µM] followed by cervical [HeLa-46.17 µM], colon [SW480- 47.28 µM], liver [HepG2- 69.56 µM] and breast [MCF-7- 84.31 µM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 µM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, ß-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS in A375 cells (IC50-24.01 µM), with that in SK-MEL-2 (IC50-67.6 µM), another melanoma cells which highly over-express MITF-M. The compound arrests the cells at S-G2 transition state of the cell cycle, as resveratrol. Our results indicate that DETS is a powerful antioxidant, having anticancer efficacy comparable with that of resveratrol, and is a potential candidate to be explored by in vivo studies and in-depth mechanistic evaluation. To our knowledge, this is the first report on the antioxidant and anticancer properties of DETS.

An in vitro study reveals the nutraceutical potential of punicic acid relevant to diabetes via enhanced GLUT4 expression and adiponectin secretion.

The prevalence of diabetes and heart diseases is increasing in the world. Nutraceuticals of natural origin are gaining importance as an alternative to modern drugs for the management of metabolic syndrome. In the present study, punicic acid (PA), a major bioactive found in pomegranate seed, was subjected for biological characterization with respect to peroxisome proliferator-activated receptor gamma (PPARγ) agonist property in an in vitro system (3T3-L1 adipocytes). We evaluated the adipogenic potential of various concentrations (5, 10 and 30 µM) of PA by studying triglyceride accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity in adipocytes, which were found to be increased moderately compared with the positive control, i.e. rosiglitazone (RG). Glucose uptake activity (↑225.93% ± 2.55% for 30 µM of PA), and the prevention of reactive oxygen species (ROS) generation (↓57 ± 1.83% for 30 µM of PA) in adipocytes with PA were also evaluated. We also found that PA increased adiponectin secretion and upregulated GLUT4 expression and translocation in adipocytes. Molecular modelling studies revealed a high binding affinity of PA to the PPARγ ligand binding domain. An in vitro ligand binding assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) also proved PA as a PPARγ agonist. Finally, we conclude that PA is a potential nutraceutical and should be encouraged for use both as a prophylactic and therapeutic agent.