Identification of key biomarkers involved in osteosarcoma using altered modules.

The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by tracking altered modules. Protein-protein interaction (PPI) networks of OS and normal groups were constructed and re-weighted using the Pearson correlation coefficient (PCC), respectively. The condition-specific modules were explored from OS and normal PPI networks using a clique-merging algorithm. Altered modules were identified by a maximum weight bipartite-matching method. The important biological pathways in OS were identified by a pathway-enrichment analysis using genes from disrupted modules. The most important genes in these pathways were selected as key biomarkers. Finally, the mRNA and protein expressions of hub genes in OS bone tissues were analyzed using reverse transcription-polymerase chain reaction and western blotting, respectively. We identified 703 and 2270 modules in normal and disease networks, respectively; 150 altered modules were identified from among these and explored. We identified 10 important pathways based on gene pairs with altered PCC > 1 in the disrupted modules (P < 0.01), and PCNA, ATP6V1C2, ATP6V1G3, FEN1, CDC7, and RPA3 (expressed in these pathways) were selected as key genes of OS. We observed that these genes (and the proteins they encoded) were differentially expressed between normal and OS samples (P < 0.01) (excluding ATP6V1C2, whose protein expression did not differ significantly). Therefore, we identified 5 gene signatures that may be potential biomarkers for the detection and effective therapy of OS.

Counterion-hopping along the backbone of single-stranded DNA in nanometer pores: a mechanism for current conduction.

Molecular dynamics calculations are performed to investigate ionic current conduction through nanopores in the presence of single-stranded DNA. We find the counterions to be strongly attracted to the phosphate groups of the DNA, with resident time on the order of nanoseconds, while coions are strongly excluded. The diffusion constant of the counterions is calculated and used to estimate the ionic current through the pore, which gives a similar magnitude as in experiment. The results suggest a counterion-hopping mechanism along the ssDNA backbone in the current conduction through nanopores.

Molecular self-diffusion in nanoscale cylindrical pores and classical Fick's law predictions.

Molecular-dynamics calculations are carried out to study the self-diffusion of water molecules confined in cylindrical pores. It is found that the classical Fick's law description provides a surprisingly accurate prediction for the general behaviors of self-diffusion even for pore size of a few molecular diameters. The diffusion coefficient in the axial direction is reduced relative to bulk fluids for pore size less than about ten molecular diameters. In the radial direction, the mean-square displacement accurately follows Fick's law prediction, but with an average diffusion coefficient slightly lower than the bulk value. The origin of the diffusion behaviors is traced to the molecular motion in the restricted geometry of the cylindrical pores.

Structure of a sheared soft-disk fluid from a nonequilibrium potential.

The distortion of structure of a simple, inverse-12, soft-disk fluid undergoing two-dimensional plane Couette flow was studied by nonequilibrium molecular dynamics (NEMD) simulation and by equilibrium Monte Carlo (MC) simulation with a nonequilibrium potential, under which the equilibrium structure of the fluid is that of the nonequilibrium fluid. Extension of the iterative predictor-corrector method of [Phys. Rev. A 33, 3451 (1986)]] was used to extract the nonequilibrium potential with the structure input from the NEMD simulation. Very good agreement for the structural properties and pressure tensor generated by the NEMD and MC simulation methods was found, thus providing the evidence that nonequilibrium liquid structure can be accurately reproduced via simple equilibrium simulations or theories using a properly chosen nonequilibrium potential. The method developed in the present study and numerical results presented here can be used to guide and test theoretical developments, providing them with the "experimental" results for the nonequilibrium potential.

Distribution functions of a simple fluid under shear. II. High shear rates.

The distortion of structure of a simple, inverse 12 soft-sphere fluid undergoing plane Couette flow is studied by nonequilibrium molecular dynamics (NEMD) and equilibrium molecular dynamics (EMD) with a high-shear-rate version of the nonequilibrium (NE) potential obtained recently from the NE distribution function theory of Gan and Eu [Phys. Rev. A 45, 3670; 46, 6344 (1992)]. The theory suggests a NE potential under which the equilibrium structure of the fluid is that of a NE fluid, and also suggests a corresponding Ornstein-Zernike equation with its closure relations. As in the low-shear-rate case [Yu. V. Kalyuzhnyi, S. T. Cui, P. T. Cummings, and H. D. Cochran, Phys. Rev. E 60, 1716 (1999)] the agreement between EMD and the modified hypernetted chain version of the theory is good. Although the high-shear-rate version of the NE potential improves the agreement between NEMD and EMD results (in comparison with the low-shear-rate version), its predictions are still unsatisfactory. With the high-shear-rate NE potential, EMD gives qualitatively correct predictions only for the shift of the position of the first maximum of the NE distribution function. The corresponding changes in the magnitude of the first maximum predicted by EMD have an opposite direction in comparison with those predicted by NEMD. It is concluded that the NE potential used is not very successful, and more accurate models for the potential are needed.

Distribution functions of a simple fluid under shear: low shear rates.

Anisotropic pair distribution functions for a simple, soft sphere fluid at moderate and high density under shear have been calculated by nonequilibrium molecular dynamics, by equilibrium molecular dynamics with a nonequilibrium potential, and by a nonequilibrium distribution function theory [H. H. Gan and B. C. Eu, Phys. Rev. A 45, 3670 (1992)] and some variants. The nonequilibrium distribution function theory consists of a nonequilibrium Ornstein-Zernike relation, a closure relation, and a nonequilibrium potential and is solved in spherical harmonics. The distortion of the fluid structure due to shear is presented as the difference between the nonequilibrium and equilibrium pair distribution functions. From comparison of the results of theory against results of equilibrium molecular dynamics with the nonequilibrium potential at low shear rates, it is concluded that, for a given nonequilibrium potential, the theory is reasonably accurate, especially with the modified hypernetted chain closure. The equilibrium molecular-dynamics results with the nonequilibrium potential are also compared against the results of nonequilibrium molecular dynamics and suggest that the nonequilibrium potential used is not very accurate. In continuing work, a nonequilibrium potential better suited to high shear rates [H. H. Gan and B. C. Eu, Phys. Rev. A 46, 6344 (1992)] is being tested.

Transient rheology of a polyethylene melt under shear.

Using nonequilibrium molecular dynamics simulation, we have studied the response of a C100 model polymer melt to a step change from equilibrium to a constant, high shear rate flow. The transient shear stress of the model polymer melt exhibits pronounced overshoot at the strain value predicted by the reptation model, in striking similarity to melts of longer, entangled polymer governed by reptation motion. At the maximum of shear stress overshoot, the molecular orientational order and the alignment angle are found to be midway between those characteristic of Newtonian flow and full alignment with the flow. The Doi-Edwards theory is found to be applicable but only by taking into account the shear-rate-dependence of the terminal relaxation time. We further analyze the molecular origins of such behavior in short polymer chains by decomposing the total stress into the contributions from various molecular interactions.