Synthesis and structure-function study of artificial nucleases on the basis of hemin conjugates with peptide fragments of cell differentiation factor HLDF

A series of octa-hexapeptide fragments of HLDF and their conjugates with hemin were obtained by solid phase peptide synthesis. A relationship between the structure and the nuclease activity of the compounds was established. The effect of various factors (medium pH, the presence of metal ions, complexons, reducers, and buffer composition) on the DNA destruction with hemin peptides was studied. Preliminary information confirming an oxidative mechanism of this process was obtained. The cleavage of plasmid DNA under the action of hemin peptides was studied by the methods of electron microscopy, gel electrophoresis, and atomic force microscopy.     

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.     

Ligand binding and dynamics of the monomeric epidermal growth factor receptor ectodomain

The ectodomain of the human epidermal growth factor receptor (hEGFR) controls input to several cell signalling networks via binding with extracellular growth factors. To gain insight into the dynamics and ligand binding of the ectodomain, the hEGFR monomer was subjected to molecular dynamics simulation. The monomer was found to be substantially more flexible than the ectodomain dimer studied previously. Simulations where the endogeneous ligand EGF binds to either Subdomain I or Subdomain III, or where hEGFR is unbound, show significant differences in dynamics. The molecular mechanics Poisson–Boltzmann surface area method has been used to derive relative free energies of ligand binding, and we find that the ligand is capable of binding either subdomain with a slight preference for III. Alanine‐scanning calculations for the effect of selected ligand mutants on binding reproduce the trends of affinity measurements. Taken together, these results emphasize the possible role of the ectodomain monomer in the initial step of ligand binding, and add details to the static picture obtained from crystal structures. Proteins 2013; 81:1931–1943. © 2013 The Authors. Proteins published by Wiley Periodicals, Inc.     

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.     

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.     

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⁺.     

Numerical Models for the Simulation of Flexible Artificial Heart Valves: Part I - Computational Methods

Abstract

A numerical model of the coupled motion of a flexing surface in a high Reynolds number flow is presented for the simulation of flexible polyurethane heart valves in the aortic position. This is achieved by matching a Lagrangian dynamic leaflet model with a panel method based flow solver. The two models are coupled via the time-dependent pressure field using the unsteady Bernoulli equation.

Incorporation of sub-cycling in the dynamic model equations and fast pre conditioning techniques in the panel method solver yields efficient convergence and near real-time simulations of valve motion. The generality of dynamic model allows different material properties and/or geometries to be studied easily and interactively. This interactivity is realized by embedding the models within a design environment created using the software IRIS Explorer ^TM.

Two flow domains are developed, an infinite domain and an internal domain using conformal mapping theory. In addition bending stress on the valve is computed using a simple stress model based on spline and circle equation techniques.     

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.     

Solid-phase distribution of heavy metals as affected by single reagent extraction in dredged sediment derived surface soils

ABSTRACT

EDTA is useful to assess mobile metal pools in polluted soils and sediments. There is a need to enhance our understanding of the significance of metal fractions released. The impact of single reagent extraction with 0.05 mol L^?1 EDTA on the solid phase distribution of trace metals in surface soils sampled from confined dredged sediment disposal sites was investigated. Not extracted and EDTA extracted soils were subjected to sequential extraction to fractionate the total contents into: (1) easily exchangeable and carbonate bound fraction; (2) reducible fraction; (3) oxidisable fraction; and (4) residual fraction. With EDTA, significant portions of metals associated with the acid extractable and reducible fractions were released. The oxidisable and residual fractions remained unaffected for most of the investigated metals except for the organic matter associated metals (Cu and Pb). A decrease in the residual fraction after EDTA-extraction for Cu and Pb was attributed to artifacts of the sequential extraction procedure.     

The effect of harvest date and harvest method on the combustion characteristics of Miscanthus × giganteus

Miscanthus × giganteus is an energy crop with many attributes that make it a potential biofuel feedstock. This study examined the chemical composition of M. × giganteus stems cut at different dates throughout the spring harvest window (January, February and March) and either left in a swath or left flat in a thin layer on the ground and compared the composition to that of the standing crop collected on the same date in April (control). The research then examined the effect of cutting date on the chemical composition of whole plant M. × giganteus biomass (leaf and stem). The parameters examined in both parts of this experiment were lower heating value on a wet basis (LHV_WB), ash, chlorine, potassium, nitrogen, sulphur, carbon and hydrogen content. The range of values recorded for the parameters from both aspects of this trial were LHV_WB 4.84–11.87 MJ kg^?1; ash 1.44–1.97%; Cl 0.07–0.23%; K 0.15–0.32%; N 0.28–0.39%; S 0.13–0.19%; C 46.75–50.00%; H 5.76–6.09%. The length of time that the M. × giganteus remained in the field after cutting affected the LHV_WB (increased with time) of the stem biomass material. Cutting the biomass and leaving it in the field lowered the ash, Cl and C content of the stem material compared to that of the control which was cut and collected on the same date. No differences were observed for the other parameters. Date of harvest affected the LHV_WB, Cl and C content which all improved with later cutting dates. Thus, combustion quality can be improved by delaying the harvest date or by cutting the crop and leaving it in the field for a period prior to collection. Choosing the correct combination of time and harvest method can therefore improve biomass fuel quality.