Adaptive steered molecular dynamics: validation of the selection criterion and benchmarking energetics in vacuum

The potential of mean force (PMF) for stretching decaalanine in vacuum was determined earlier by Park and Schulten [J. Chem. Phys. 120, 5946 (2004)] in a landmark article demonstrating the efficacy of combining steered molecular dynamics and Jarzynski's nonequilibrium relation. In this study, the recently developed adaptive steered molecular dynamics (ASMD) algorithm [G. Ozer, E. Valeev, S. Quirk, and R. Hernandez, J. Chem. Theory Comput. 6, 3026 (2010)] is used to reproduce the PMF of the unraveling of decaalanine in vacuum by averaging over fewer nonequilibrium trajectories. The efficiency and accuracy of the method are demonstrated through the agreement with the earlier work by Park and Schulten, a series of convergence checks compared to alternate SMD pulling strategies, and an analytical proof. The nonequilibrium trajectories obtained through ASMD have also been used to analyze the intrapeptide hydrogen bonds along the stretching coordinate. As the decaalanine helix is stretched, the initially stabilized i → i + 4 contacts (α-helix) is replaced by i → i + 3 contacts (3(10)-helix). No significant formation of i → i + 5 hydrogen bonds (π-helix) is observed.     

Objective Bayesian Model Selection in Generalized Additive Models With Penalized Splines

We propose an objective Bayesian approach to the selection of covariates and their penalized splines transformations in generalized additive models. The methodology is based on a combination of continuous mixtures of g-priors for model parameters and a multiplicity-correction prior for the models themselves. We introduce our approach in the normal model and extend it to nonnormal exponential families. A simulation study and an application with binary outcome is provided. An efficient implementation is available in the R package hypergsplines. Supplementary materials for this article are available online.     

Crystal growth and characterization of a new co-ordination complex—barium tetrakis(maleate) dihydrate

Crystals of barium tetrakis(maleate) dihydrate [Ba₄(C₄H₂O₄)₄]^?2H₂O are grown in gelated hydrosilica matrix. Single crystal X-ray diffraction studies show that the crystal system is monoclinic with space group P2₁/c. The unit cell dimensions are a=9.3721(2)  Å, b=20.5880(7)  Å, c=14.0744(4) Å, α=γ=90°, β=90.289(2)°. Powder XRD studies confirmed the single phase nature of the grown crystals. The FTIR data is in conformity with the XRD results. The TG–DTA curves of the material indicate a three-step thermal decomposition. The response of the dielectric properties in the temperature range 30 °C to 500 °C is correlated with the TG–DTA results.     

Lie group analysis of gravity currents

We consider shallow water theory to study the self-similar gravity currents that describe the motion of a heavy fluid flowing into another lighter ambient fluid. Gratton and Vigo investigated the shallow water theory representing the self-similar gravity currents by using dimensional analysis [J. Gratton, C. Vigo, Self-similarity gravity currents with variable inflow revisited: Plane currents, J. Fluid. Mech. 258 (1994) 77–104]. But in this study, the self-similarity solutions of the one-layer shallow-water equations representing gravity currents are investigated by using Lie group analysis and it is shown that Lie group analysis is the generalization of the dimensional analysis for investigating the self-similarity solutions of the one-layer shallow-water equations. Applying Lie group theory, reduced equations of the shallow water equations are found. Therefore, it becomes possible to obtain the similarity forms depending on the Lie group parameters and also the self-similarity solutions for the special values of these group parameters.     

Modeling and control of a nonlinear half-vehicle suspension system: a hybrid fuzzy logic approach

Modeling and control of vehicle suspension system are high noteworthy from safety to comfort. In this paper, an analytical nonlinear half-vehicle model which is included quadratic tire stiffness, cubic suspension stiffness, and coulomb friction is derived based on fundamental physics. A hybrid fuzzy logic approach which combines fuzzy logic and PID controllers is designed for reducing the vibration levels of passenger seat and vehicle body. Performances of designed controllers have been evaluated by numerical simulations. Comparisons with classical PID control, Fuzzy Logic Control (FLC) and Hybrid Fuzzy-PID control (HFPID) have also been provided. Results of numerical simulations are evaluated in terms of time histories of displacement and acceleration responses and ride index comparison. A good performance for the Hybrid Fuzzy-PID controller with coupled rules (HFPIDCR) is achieved in simulation studies despite the nonlinearities.     

Anti-Quorum Sensing Activity of Stevia Extract,Stevioside, Rebaudioside A and Their Aglycon Steviol

Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers have turned their attention to natural dietary sweeteners, such as stevia, to meet their sweetening needs. Stevia is generally considered safe; however, emerging scientific evidence has implicated the agent in gut microbial imbalance. In general, regulation of microbial behavior is known to depend highly on signaling molecules via quorum sensing (QS) pathways. This is also true for the gut microbial community. We, therefore, evaluated the possible role of these stevia-based natural sweeteners on this bacterial communication pathway. The use of a commercial stevia herbal supplement resulted in an inhibitory effect on bacterial communication, with no observable bactericidal effect. Purified stevia extracts, including stevioside, rebaudioside A (Reb A), and steviol revealed a molecular interaction, and possible interruption of Gram-negative bacterial communication, via either the LasR or RhlR receptor. Our in-silico analyses suggest a competitive-type inhibitory role for steviol, while Reb A and stevioside are likely to inhibit LasR-mediated QS in a non-competitive manner. These results suggest the need for further safety studies on the agents.     

Liquid chromatography/tandem mass spectrometry based targeted proteomics quantification of P-glycoprotein in various biological samples

P-Glycoprotein (P-gp/ABCB1) is expressed in membrane barriers to exclude pharmacological substrates from cells, and therefore influences the ADME/Tox properties and efficacy of therapeutics. In the present study, a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-mediated targeted proteomics was developed to quantitate P-gp protein. With the aid of in silico predictive tools, a unique 9-mer tryptic peptide of P-gp protein was synthesized (with the stable isotope labeled (SIL) peptide as internal standard) and applied for quantitative LC/MS/MS method development. For LC/MS/MS quantification, the N-glycosylation of the peptide, polymorphism and transmembrane region was intended to be excluded during the peptide selection. The lower limit of quantification was established to be 0.025 nM with the linearity of the standard curve ranging to 20 nM of P-gp signature peptides in the matrix digested surrogate bovine serum albumin. The digestion efficiency, both the accuracy (relative error) and the precision (coefficient of variation) of the method, was verified by using the synthetic quantification peptide and the synthetic surrogate substrate peptide that mimics the sequence of tryptic peptide and associated flanking tryptic cleavage sites at the N- and C-terminals. By applying the method developed, the absolute amounts of human, dog and mouse P-gp (Mdr1a) were quantified in various biological samples. LC/MS/MS-mediated P-gp quantification was achieved as a highly sensitive, selective and reproducible assay and could be directly applicable to many current research needs related to P-gp.