Atomic radius and charge parameter uncertainty in biomolecular solvation energy calculations

Atomic radii and charges are two major parameters used in implicit solvent electrostatics and energy calculations. The optimization problem for charges and radii is under-determined, leading to uncertainty in the values of these parameters and in the results of solvation energy calculations using these parameters. This paper presents a new method for quantifying this uncertainty in implicit solvation calculations of small molecules using surrogate models based on generalized polynomial chaos (gPC) expansions. There are relatively few atom types used to specify radii parameters in implicit solvation calculations; therefore, surrogate models for these low-dimensional spaces could be constructed using least-squares fitting. However, there are many more types of atomic charges; therefore, construction of surrogate models for the charge parameter space requires compressed sensing combined with an iterative rotation method to enhance problem sparsity. We demonstrate the application of the method by presenting results for the uncertainties in small molecule solvation energies based on these approaches. The method presented in this paper is a promising approach for efficiently quantifying uncertainty in a wide range of force field parameterization problems, including those beyond continuum solvation calculations.The intent of this study is to provide a way for developers of implicit solvent model parameter sets to understand the sensitivity of their target properties (solvation energy) on underlying choices for solute radius and charge parameters

Inclusion of frequency control constraints in energy system investment modeling

This study investigates how the inclusion of frequency control constraints in electricity system modeling impacts the levels of investment and dispatch in electricity generation and storage technologies for futures that include high-level penetration of variable renewable energy. This is achieved using a linear cost-minimizing investment and dispatch model using historic load, wind and solar conditions from Spain, Ireland, Sweden and Hungary for Year 2050. With an hourly time-resolution, constraints are added so as to ensure that, within each hour, sufficient inertial power and reserves are available to control the frequency of the power grid. Comparing the results obtained with and without these constraints reveals that the main impacts on the results are from battery investments and operation. Furthermore, it is found that the reserve requirements exert a greater impact on system composition and operation than do the inertial power requirements

Frequency control and synthetic inertia in energy systems modelling

This study investigates how inclusion of frequency control constraints in electricity system modelling impacts the investment and dispatch in electricity generation and storage technologies for high-VRE futures. This is done using a linear cost-minimizing investment and dispatch model using historical load, wind and solar power conditions from Spain, Ireland, Sweden and Hungary for the year 2050. With an hourly time-resolution, constraints are added to ensure that, within each hour, sufficient inertial power and reserves are available to control the frequency. Comparing the results with and without these constraints show that nearly all impact on the results is in battery investments and operation. Furthermore, it is found that reserve requirements have a higher impact on system composition and operation than inertial power requirements

Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis

SummaryHox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters

An Architecture for Computer-Aided Detection and Radiologic Measurement of Lung Nodules in Clinical Trials

Computer tomography (CT) imaging plays an important role in cancer detection and quantitative assessment in clinical trials. High-resolution imaging studies on large cohorts of patients generate vast data sets, which are infeasible to analyze through manual interpretation