Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Experimental study of the operating characteristics of a heat pump assisted distillation system using R11 as the external working fluid

Heat pump assisted distillation with an external working fluid is one of the most obvious methods to reduce the energy consumption in a distillation process. The heat pump working fluid extracts heat from the top of the column, increases the temperature of the recovered heat and recycles it to provide the heat input to the reboiler. The interaction between the external parameters and the internal parameters for a specially designed heat pump assisted distillation system has been studied experimentally. The external parameters were mass flow rate, temperature and concentration of the feed, the concentration of the top and bottom products and the mass flow rate of the working fluid. The effects of the variations of these external parameters on the internal parameters such as the energy (steam) consumption, the actual coefficient of performance and the temperatures at the top and bottom of the column, together with the condensation and evaporation temperatures, are presented.

Assessing the Impact of Interactive Sea Level Rise Maps in New Zealand

Sea level rise (SLR) due to climate change is a global threat. Interactive maps illustrate the effects of SLR for the public but their impact is unclear. We conducted interviews with map developers, climate change scientists, and science communication experts, and distributed a public survey, to understand how best to engage the public. We determined that interactive maps are not the most effective method of SLR communication, and we recommend that NZ SeaRise develop a centralized platform for all information regarding SLR

Evaluation of CM5 Charges for Nonaqueous Condensed-Phase Modeling

Partial atomic charges for neutral molecules from quantum mechanical calculations are typically scaled for use in molecular modeling of liquid-phase systems. Optimal scale factors of 1.14 for CM1A and 1.27 for CM5 charges were previously determined for minimizing errors in free energies of hydration. The adequacy of the 1.14*CM1A and 1.27*CM5 models are evaluated here in pure liquid simulations in combination with the OPLS-AA force field. For 22 organic liquids, the 1.14*CM1A and 1.27*CM5 models yield mean unsigned errors (MUEs) of ca. 1.40 kcal/mol for heats of vaporization. Not surprisingly, this reflects overpolarization with the scale factors derived for aqueous media. Prediction of pure liquid properties using CM5 charges is optimized using a scale factor of 1.14, which reduces the MUE for heats of vaporization to 0.89 kcal/mol. However, due to the impracticality of using different scale factors in different explicit-solvent condensed-phase simulations, a universal scale factor of 1.20 emerged for CM5 charges. This provides a balance between errors in computed pure liquid properties and free energies of hydration. Computation of free energies of hydration by the GB/SA method further found that 1.20 is equally suited for use in explicit or implicit treatments of aqueous solvation. With 1.20*CM5 charges, a variety of condensed-phase simulations can be pursued while maintaining average errors of 1.0 kcal/mol in key thermodynamic properties

1.14*CM1A-LBCC: Localized Bond-Charge Corrected CM1A Charges for Condensed-Phase Simulations

The quality of the 1.14*CM1A and 1.20*CM5 charge models was evaluated for calculations of free energies of hydration. For a set of 426 neutral molecules, 1.14*CM1A and 1.20*CM5 yield MADs of 1.26 and 1.21 kcal/mol, respectively. The 1.14*CM1A charges, which can be readily obtained for large systems, exhibit large deviations only for a subset of functional groups. The results for these cases were systematically improved using localized bond-charge corrections (LBCC) by which offsetting adjustments are made to the partial charges for atoms in specified bond types. Only 19 LBCCs were needed to yield 1.14*CM1A-LBCC charges that reduce the errors for the 426 <i>Δ<i>G</i></i>_hyd values to only 0.61 kcal/mol. The modified charge method was also tested in computation of heats of vaporization and densities for pure organic liquids, yielding average errors of 1.40 kcal/mol and 0.024 g/cm³, similar to those for 1.14*CM1A