Surface Area Model Research Articles

Genomic structural equation modeling reveals latent phenotypes in the human cortex with distinct genetic architecture

Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for 34 brain regions recently reported in the ENIGMA cortical GWAS. Genomic SEM uses the empirical genetic covariance estimated from GWAS summary statistics with LD score regression (LDSC) to discover factors underlying genetic covariance, which we are denoting genetically informed brain networks (GIBNs). Genomic SEM can fit a multivariate GWAS from summary statistics for each of the GIBNs, which can subsequently be used for LD score regression (LDSC). We found the best-fitting model of cortical SA identified 6 GIBNs and CT identified 4 GIBNs, although sensitivity analyses indicated that other structures were plausible. The multivariate GWASs of the GIBNs identified 74 genome-wide significant (GWS) loci (p < 5 × 10−8), including many previously implicated in neuroimaging phenotypes, behavioral traits, and psychiatric conditions. LDSC of GIBN GWASs found that SA-derived GIBNs had a positive genetic correlation with bipolar disorder (BPD), and cannabis use disorder, indicating genetic predisposition to a larger SA in the specific GIBN is associated with greater genetic risk of these disorders. A negative genetic correlation was observed between attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD). CT GIBNs displayed a negative genetic correlation with alcohol dependence. Even though we observed model instability in our application of genomic SEM to high-dimensional data, jointly modeling the genetic architecture of complex traits and investigating multivariate genetic links across neuroimaging phenotypes offers new insights into the genetics of cortical structure and relationships to psychopathology.

Development and test of highly accurate endpoint free energy methods. 3: partition coefficient prediction using a Poisson-Boltzmann method combined with a solvent accessible surface area model for SAMPL challenges.

Accurately predicting solvation free energy is the key to predict protein-ligand binding free energy. In addition, the partition coefficient (log P), which is an important physicochemical property that determines the distribution of a drug in vivo, can be derived directly from transfer free energies, i.e., the difference between solvation free energies (SFEs) in different solvents. Within the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) 9 challenge, we applied the Poisson-Boltzmann (PB) surface area (SA) approach to predict the toluene/water transfer free energy and partition coefficient (log Ptoluene/water) from SFEs. For each solute, only a single conformation automatically generated by the free software Open Babel was used. The PB calculation directly adopts our previously optimized boundary definition - a set of general AMBER force field 2 (GAFF2) atom-type based sphere radii for solute atoms. For the non-polar SA model, we newly developed the solvent-related molecular surface tension parameters γ and offset b for toluene and cyclohexane targeting experimental SFEs. This approach yielded the highest predictive accuracy in terms of root mean square error (RMSE) of 1.52 kcal mol-1 in transfer free energy for 16 small drug molecules among all 18 submissions in the SAMPL9 blind prediction challenge. The re-evaluation of the challenge set using multi-conformation strategies based on molecular dynamics (MD) simulations further reduces the prediction RMSE to 1.33 kcal mol-1. At the same time, an additional evaluation of our PBSA method on the SAMPL5 cyclohexane/water distribution coefficient (log Dcyclohexane/water) prediction revealed that our model outperformed COSMO-RS, the best submission model with RMSEPBSA = 1.88 versus RMSECOSMO-RS = 2.11 log units. Two external log Ptoluene/water and log Pcyclohexane/water datasets that contain 110 and 87 data points, respectively, are collected for extra validation and provide an in-depth insight into the error source of the PBSA method.

Design and thermal performance analysis of different type cylindrical heatsinks

Reducing the junction temperature of a light emitting diode (LED) to a specific temperature is critical for the luminaires' lifetime and illumination performance. To attain a low junction temperature, a reference radial cylindrical heatsink with was constructed. This model was accepted as a starting point, then nine further models were created using various geometric alterations. The three basic versions with 24 channels: Pin Fin (PF), Pin Vawy Fin (PWF), and Cross-Cut Fin (CCF) were produced by milling machine. These three models were numerically analyzed under the identical conditions and experimental results were confirmed. Then the models were compared in depth using numerical analyses of 3W, 7W, and 10W. The CCF-Y model's surface area has expanded by 24%, and its thermal performance has increased by about 5%, thanks to the radial and axial thin channels that were developed.

Estimation of surface area of methane hydrate in the sand sediment using a dissociation-rate model

Estimation of surface area of methane hydrate in sub-seabed sand sediment is important to predict the production rate of methane gas. The surface area depends on the morphology of hydrate in the sediment: i.e., how the methane hydrate exists in the sediment. First, we conducted heat-transfer experiment and numerical simulations with the same conditions of pressure and temperature, and confirmed that the thermal conductivity for the mixture of sand grains, water, gas, and hydrate follows a random model. Then, we conducted hydrate-dissociation experiments by depressurisation in a high-pressure cell packed with glass beads with changing porosity, hydrate saturation, and size of sediment particles. We proposed a model equation for specific surface area of hydrate in the sediment as a function of porosity, hydrate saturation, and the size of sediment particles. We also conducted numerical simulations of the heat transfer, using numerical models both for the dissociation of hydrate and the thermal conductivity of gas–water–sand–hydrate mixture. As a result, the proposed model equation for the specific surface area of hydrate was performed well in a validation by comparing the temporal changes of measured total gas production and its rate. We believe that this hydrate surface-area model can be applied to the numerical prediction of gas production from hydrate-bearing sediments.

Dissolution behavior of (U,Zr)O2-based simulated fuel debris in nitric acid

To explore the possibility of dissolving fuel debris into nitric acid as a potential pre-treatment for waste treatment in which the U and Pu are removed from the inventory, dissolution tests of U1−xZrxO2 and (U,Pu)1−xZrxO2 were carried out in 6 M HNO3 at 353 K. At the end of the dissolution test (after 4 h), the ratio of dissolved uranium decreased with an increase in the Zr contents, x. While the dissolution of U-rich samples was congruent, a preferential leaching of U was observed with Zr-rich samples. Taking into account these different dissolution phenomena, the dissolution rate analysis was carried out using surface-area model to calculate the instantaneous dissolution rate (IDR). The IDR decreased from 10−5 down to 10−10 mol cm−2 min−1 as x increased from 0 to 0.95. From these findings, dissolution with HNO3 is expected to be only applicable in U-rich part of fuel debris (x < 0.3) if the dissolution in 6 M HNO3 at 353 K is assumed. Application of complexing acids, such as mixture of HNO3 and HF, should be considered to increase the dissolution rate of the Zr-rich part.

Improved protein–ligand binding affinity prediction by using a curvature-dependent surface-area model

Hydrophobic effect plays a pivotal role in most protein-ligand binding. State-of-the-art protein-ligand scoring methods usually treat hydrophobic free energy as surface tension, which is proportional to interfacial surface area for simplicity and efficiency. However, this treatment ignores the role of molecular shape, which has been found very important by either experimental or theoretical studies. We propose a new empirical scoring function, named Cyscore. Cyscore improves the prediction accuracy by using a novel curvature-dependent surface-area model, which is able to distinguish convex, planar and concave surface in hydrophobic free energy calculation. Benchmark tests show that this model significantly improves the protein-ligand scoring and Cyscore outperforms a variety of well established scoring functions using PDBbind benchmark sets for binding affinity correlation and ranking tests. We expect the curvature-dependent surface-area model and Cyscore would contribute to the study of protein-ligand interactions. Cyscore is available to non-commercial users at http://clab.labshare.cn/software/cyscore.html.

Estimation of the Formation Rate Constant of Methane Hydrate in Porous Media

Summary Hydrate formation and the relevant mass and heat transfers were numerically analyzed in a microscopic computational domain in which spherical glass beads, water, and methane gas were distributed separately. A hydrate-formation experiment was also carried out by use of a cylindrical pressure cell. The temperature in the cell was controlled by Peltier devices, which were attached to the outer walls of the cell to imitate the adiabatic boundary condition present in the numerical simulation. By history matching between the experiment and calculation, we first obtained a hydrate-formation rate constant per unit volume of water, assuming homogeneous nucleation. Then, after converting the rate by use of a surface-area model of water in porous media, we noted that the area-based rate constant and activation energy of the hydrate formation were estimated to be 6.33 × 1034 mol·m–2 Pa–1 s–1 and 238 × 103 J/mol, respectively, for temperatures of 1.5 to 3.4°C.

Dissolution Behavior of Irradiated Mixed-oxide Fuels with Different Plutonium Contents

The effects of Pu content on the dissolution rate and the mass of the insoluble residue of irradiated mixed oxide fuel were studied. On the basis of the kinetic analysis assuming the surface-area model, the dissolution rate was found to decrease exponentially with an increase of the Pu content, but those were estimated to be up to 103 times larger than non-irradiated fuels. The mass of the insoluble residue tended to increase with an increase of the Pu content, possibly due to the promotion of fission product formation and an increase of refractory Pu enriched zone.

Binding Sites of the E. Coli DNA Recombinase Protein to the ssDNA: A Computational Study

Homologous recombination (HR) is a major pathway for the repair of double strand breaks, which is of primary importance for genomic stability and survival of all organisms. The crucial step in HR is the formation of the nucleoprotein filament composed by a single stranded DNA chain surrounded by the recombinases protein. The filament leads the search for an undamaged homologue, a sister-chromatid or homologous chromosome, as a template for the repair process. The theoretical study presented in this work is aimed to increase the understanding of the mechanism of interaction between a trimer of the recombinase enzyme in the Escherichia coli, EcRecA, with a model system of single stranded DNA, dT9. The molecular dynamics (MD) calculations were performed using the Amber 10 computer code. The binding free energies are calculated with the Molecular Mechanics (MM) Poisson-Boltzmann (PB) and Generalized Born (GB) solvent accessible surface area (SA), MM-PB(GB) SA model. The study is extended by the use of the Principal Component Analysis (PCA) to reduce the dimensionality of the conformational space. Several mutants are considered and the corresponding calculated binding free energies are compared. An experimental correlation between the binding free energy and the enzyme activity is absent in the literature, however our results confirm how the wild type RecA has a higher binding affinity compared to the mutants examined. Moreover, for all cases considered, a significant contribution of the binding free energy is due to one amino-acid, R196, located in the binding loop 2 of the enzyme. This is consistent with the complete loss of the enzyme activity for any mutation on that point.

Binding energetics of the inhibitor cystatin to the cysteine proteinase actinidin.

The binding energetics of actinidin to chicken cystatin was determined from fluorometric titrations at different temperatures. It is shown that the association of actinidin with cystatin is both enthalpically and entropically driven, with a negative change in the heat capacity. The molecular basis of these contributions are analyzed within the framework of surface-area models, using a 3D model of the actinidin-cystatin complex, which was obtained using the x-ray structure of the homologous complex papain-stefin B as template.

Hydrophobic Force Field as a Molecular Alternative to Surface-Area Models

An effective force field for hydrophobic interactions is developed based on a modified potential-of-mean-force (PMF) expansion of the effective many-body interactions between nonpolar molecules in water. For the simplest nonpolar solutes in water, hard particles, the modified PMF expansion is exact in both limiting cases of infinite separation and perfect overlap. The hydrophobic interactions are parametrized by using the information-theory model of hydrophobic hydration. The interactions between nonpolar solutes are short-ranged and can be evaluated efficiently on a computer. The force field is compared with simulation data for alkane conformational equilibria in water as well as a model for the formation of a hydrophobic core of a protein. The modified PMF expansion can be extended to solutes with attractive interactions. The observed accuracy, computational efficiency, and atomic detail of the model suggest that this simple hydrophobic force field can lead to a molecular alternative for phenomenologica...

Improvement of equivalent source inversion technique with a more symmetric dipole distribution model

A technique which generates an equal-area distribution model for numerical integration on the surface of a sphere by equally subdividing the faces of a spherical icosahedron was applied to the analysis of polar orbiting geophysical observatory crustal magnetic anomaly data and compared with the longitude-latitude gridding model currently being used. The region in Bangui, Central African Republic, which includes the Bangui anomaly was chosen for comparison of the two models. Using the equivalent source inversion technique and the technique of principal component regression a magnetization function was calculated for each model. With an average dipole spacing of 2.3° for each model the results indicated good correlation of the inverse solution between the models up to 99.99% of the trace retention of the singular value decomposition. At 99.99% of the trace retention, equatorial instabilities begin to arise. Further increase of the percentage of trace retention led to greater equatorial instabilities; however, the severity of the instabilities were less for the proposed model. At 99.99% of trace retention, a 15% smaller standard deviation of magnetization function was found for the proposed model than for the current model, and at 99.9999% at 42% smaller standard deviation of magnetization function was found for the proposed model. The better results seen with this model are thought to be due to the high symmetry and shape consistency of the model's surface area sectors which are qualities lacking in the longitude-latitude distribution model currently in use. The proposed model is, however, limited in that only discrete dipole spacings are possible, as opposed to the currently used model which permits a continuous range of dipole spacings.