We investigate the dielectric constant and the dielectric decrement of aqueous NaCl solutions by means of molecular dynamic simulations. We thereby compare the performance of four different force... Show moreWe investigate the dielectric constant and the dielectric decrement of aqueous NaCl solutions by means of molecular dynamic simulations. We thereby compare the performance of four different force fields and focus on disentangling the origin of the dielectric decrement and the influence of scaled ionic charges, as often used in nonpolarizable force fields to account for the missing dynamic polarizability in the shielding of electrostatic ion interactions. Three of the force fields showed excessive contact ion pair formation, which correlates with a reduced dielectric decrement. In spite of the fact that the scaling of charges only weakly influenced the average polarization of water molecules around an ion, the rescaling of ionic charges did influence the dielectric decrement, and a close-to-linear relation of the slope of the dielectric constant as a function of concentration with the ionic charge was found. Show less
Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the... Show moreBackground: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear.Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium.Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer.Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer. Show less
We investigate the dielectric constant and the dielectric decrement of aqueous NaCl solutions by means of molecular dynamic simulations. We thereby compare the performance of four different force... Show moreWe investigate the dielectric constant and the dielectric decrement of aqueous NaCl solutions by means of molecular dynamic simulations. We thereby compare the performance of four different force fields and focus on disentangling the origin of the dielectric decrement and the influence of scaled ionic charges, as often used in nonpolarizable force fields to account for the missing dynamic polarizability in the shielding of electrostatic ion interactions. Three of the force fields showed excessive contact ion pair formation, which correlates with a reduced dielectric decrement. In spite of the fact that the scaling of charges only weakly influenced the average polarization of water molecules around an ion, the rescaling of ionic charges did influence the dielectric decrement, and a close-to-linear relation of the slope of the dielectric constant as a function of concentration with the ionic charge was found. Show less
