Basic statistics and variational concepts behind the reverse Monte Carlo technique

We revise the statistical foundations of the reverse Monte Carlo (RMC) technique by constructing the associated functional of a variational principle which incorporates, without any ad hoc assumptions, the inherent errors accompanying the simulation and the experimental data. We propose a Bayesian criteria for acceptance/rejection of configurations, in terms of the variations of the functional. The loss function and variational functional minimization approaches are compared.     

Configurational Temperature for Brownian Dynamics

Abstract

Expressions for the configurational temperature are evaluated in Brownian dynamics simulations of a Lennard-Jones fluid and compared with the input temperature which is used to generate the random displacements. It is found that the two temperatures agree in the limit of large numbers of particles, and even for moderate system sizes the configurational temperature is a useful check on the correctness of the simulation algorithm. Investigation of the autocorrelation functions shows that for Lennard-Jones and power-law fluids, the correlation time of the configurational temperature is shorter than other typical thermodynamic quantities, and it generally increases with the range of the potential.     

Ab initio fragment molecular orbital calculations on the specific interactions between human,mouse and rat PPARα and GW409544

To elucidate the specific interactions between the peroxisome proliferator-activated receptor (PPARα) and ligand GW409544 (GW), we obtained the solvated structures of the PPARα+GW complexes for human, mouse and rat by classical molecular mechanics calculations, and investigated their electronic properties by ab initio fragment molecular orbital calculations. The results indicate that the positively charged amino acids (Lys and Arg) of PPARα make a major contribution to the binding between PPARα and GW. In addition, it was clarified that Ser280 and Tyr314 of human and rat PPARα have a large attractive interaction with GW, while Ser280, Tyr314 and His440 of mouse PPARα have large interaction. These results on the difference in specific interactions between human and mouse/rat PPARα will be useful for predicting the effects of new chemicals on the human body based on the biomedical studies for the experimental animals such as mouse and rat.     

The Glassy Wall Boundary for Simulations of Inhomogeneous Systems

Abstract

For simulations on systems that invlove a physical inhomogeneity at infinite dilution, the usual periodic boundary conditions are inappropriate. In previous studies on such systems, surfaces have been re-introduced in order to contain the particles of the sample. When smooth surfaces are used to contain liquids, undesirable structural artifacts in the liquid are promoted by these surfaces. In this study a rigid but structurally liquid-like containing surface, that we call a glassy wall boundary, is introduced, in an attempt to solve this problem. It serves as a containing surface, but “looks” nearly liquid-like to molecules in the mobile liquid near it. We illustrate the properties of this boundary for a system that consists of an isolated polyion surrounded by SPC water at 300K and ～ 1 gcm^?3. We show that this boundary reduces or eliminates some of the problems caused by a smooth surface.     

Molecular Mechanics Studies of Molybdenum Disulphide Catalysts Parameterisation of Molybdenum and Sulphur

Abstract

A method for the parameterisation of molybdenum disulphide is presented which reproduces the crystal structure accurately. The method involves calculating parameters such that there is no net force contribution from any individual term of the potential on any atom. Ideal bond lengths and bond angles are taken from the X-ray crystal structure; stretching and bending force constants are calculated from a combination of spectroscopic data and quantum mechanics calculations, whereby the energy function with bond length or bond angle is calculated and fitted with an harmonic potential. For the non-bonded Lennard-Jones parameters, the dispersion coefficient C was calculated by an interpolation of existing published parameters using a multiple regression and then the crystal energy was minimised with respect to the van der Waals radius r₀ using a fixed crystal fragment.

These parameters were tested for various models of the hexagonal and rhombohedral forms of MoS₂. RMS fits between structures minimised with molecular mechanics and experimental models ranged from 0.006 Å to 0.012 Å.     

Mg2+ Dependence of the Structure and Thermodynamics of Wheat Germ and Lupin Seeds 5S rRNA

Abstract

The formation and stability of structural elements in two 5S rRNA molecules from wheat germ (WG) and lupin seeds (LS) as a function of Mg²⁺ concentration in solution was determined using the adiabatic differential scanning microcalorimetry (DSC). The experimentally determined thermodynamic parameters are compared with calculations using thermodynamic databases used for prediction of RNA structure. The 5S rRNA molecules which show minor differences in the nucleotide sequence display very different thermal unfolding profiles (DSC profiles). Numerical deconvolution of DSC profiles provided information about structural transformations that take place in both 5S rRNA molecules. A comparative analysis of DSC data and the theoretical thermodynamic models of the structure was used to establish a relationship between the constituting transitions found in the melting profiles and the unfolding of structural domains of the 5S rRNA and stability of its particular helical elements.

Increased concentration of Mg²⁺ ions induces additional internal interactions stabilising 5S rRNA structures found at low Na⁺ concentrations. Observed conformational transitions suggest a structural model in which the extension of helical region E dominates over the postulated tertiary interaction between hairpin loops. We propose that helix E is stabilised by a sequence of non-standard pairings extending this helix by the formation of tetra loop e and an almost total reduction of loop d between helices E and D. Two hairpin structures in both 5S rRNA molecules: the extended C-C' and the extended E-E'-E” hairpins appear as the most stable elements of the structure. The cooperativity of the unfolding of helixes in these 5S rRNA molecules changes already at 2 mM Mg²⁺.     

The ovarian maturation cycle of the Norway lobster Nephrops norvegicus (Linnaeus, 1758) (Crustacea,Decapoda) from the western Mediterranean Sea

Summary

The Norway lobster Nephrops norvegicus lives in the continental margins of the western Mediterranean Sea at depths between 100 and 600 m. It constitutes an important fisheries resource and presents a seasonal reproductive pattern. Female Norway lobsters were obtained each month from a vessel fishing off Barcelona. One hundred females caught in June 2002 were kept in the laboratory. After spawning, ovarian samples were taken every 30 days with the objective of monitoring the first steps in ovarian maturation. The gonado-somatic index (GSI) remained low over the 6 months during which the females carried their eggs, plus for a further 2–3 months. However, this study suggests that ovarian maturation is a continuous process with two different phases, taking at least 6–8 months during which the female carries its eggs. There is an increase in oocyte numbers; the germinal zone produces oogonia; and the oocytes that develop migrate to the periphery, pushing the post-ovulatory follicles to the wall of the ovary and reinforcing it for subsequent spawning. Besides this increase in the number of oocytes, vitellogenesis begins 2–3 months after the eggs hatch. Oocytes then grow and the ovaries gain weight and change from a cream color to a blackish-green. When the GSI reached 10, spawning occurred and, from then on, the ovary is mainly composed of post-ovulatory follicles.     

Kinetics of cross-slope running

The purpose of the present study was to identify kinetic responses to running on mediolaterally elevated (cross-sloped) running surfaces. Ground reaction forces (GRFs), GRF lever arms and joint moment characteristics of 19 male runners were analyzed when running at 3.5 m/s on a custom-made, tiltable runway. Tilt angles of 3° and 6° for medial and lateral elevation were analyzed using a 10 camera Vicon Nexus system and a force platform. The point of force application of the GRF showed a systematic shift in the order of 1–1.5 cm to either the lateral or medial aspect of the foot for lateral or medial inclinations, respectively. Consequently, the strongest significant effects of tilt orientation and level on joint kinetics and ground reaction force lever arms were identified at the ankle, knee and hip joint in the frontal plane of movement. External eversion moments at the ankle were significantly increased by 35% for 6° of lateral elevation and decreased by 16% for 6° of medial elevation. Altering the cross-slope of the running surface changed the pattern of ankle joint moments in the transversal plane. Effect sizes were on average larger for laterally elevated conditions, indicating a higher sensitivity of kinetic parameters to this kind of surface tilt. These alterations in joint kinetics should be considered in the choice of the running environment, especially for specific risk groups, like runners in rehabilitation processes.     

A liquid chromatography–tandem mass spectrometry assay for d-Ala-d-Lac: A key intermediate for vancomycin resistance in vancomycin-resistant enterococci

Vancomycin exerts its antibacterial activity by binding to d-Ala-d-Ala in bacterial cell wall precursors. Vancomycin resistance in vancomycin-resistant enterococci (VRE) is due to an alternative cell wall biosynthesis pathway in which d-Ala-d-Ala is replaced, most commonly by d-Ala-d-Lac. In this study, we extend our recently developed Marfey’s derivatization-based liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for l-Ala, d-Ala, and d-Ala-d-Ala to d-Ala-d-Lac and apply it to the quantitation of these metabolites in VRE. The first step in this effort was the development of an effective washing method for removing medium components from VRE cells. Mar-d-Ala-d-Lac was well resolved chromatographically from Mar-d-Ala-d-Ala, a prerequisite for MS/MS quantitation of d-Ala-d-Ala and d-Ala-d-Lac. Mar-d-Ala-d-Lac gave similar detection parameters, sensitivity, and linearity as Mar-d-Ala-d-Ala. l-Ala, d-Ala, d-Ala-d-Ala, and d-Ala-d-Lac levels in VRE were then determined in the presence of variable vancomycin levels. Exposure to vancomycin resulted in a dramatic reduction of d-Ala-d-Ala, with a response midpoint at approximately 0.06 μg/ml vancomycin and with a broad response profile up to 128 μg/ml vancomycin. In contrast, d-Ala-d-Lac was present in the absence of vancomycin, with its level constant up to 128 μg/ml vancomycin. This method will be useful for the discovery, characterization, and refinement of new agents targeting vancomycin resistance in VRE.     

Ultrastructure and development during meiosis and the tetrad period of sporogenesis in the leptosporangiate fern Alsophila setosa (Cyatheaceae) compared with corresponding stages in Psilotum nudum (Psilotaceae)

The pre-meiotic, meiotic and tetrad stages of development in microsporangia of Alsophila setosa were studied with particular emphasis on the early establishment of patterning in the microspore wall and the subsequent development of the sporoderm. The data obtained were compared with corresponding ontogenetic stages of Psilotum nudum. Tapetal behaviour was also examined. During the tetrad period, only one layer, a thin undulating sheet, appeared alongside the plasma membrane of the tetraspores, and this was evidently formed on a pre-patterned structure – a fibrillar layer, corresponding to a kind of primexine matrix. The early free microspores had a wavy plasma membrane with a parallel, sinusoidal, thin initial sporoderm layer. The proximal apertural fold was observed to be an extended outgrowth of this initial spore envelope. Sporoderm ontogeny during the tetrad period in Alsophila and Psilotum show some common points, but also fundamental differences, mainly in the relative timing of events: in Alsophila the end of the tetrad period is the starting point for exospore development, whereas in Psilotum the exospore is already complete at this stage. Considerable differences were also observed in the tapetum of the two species.