An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models. A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance. Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded introductory and discussion sections, added corollaries, new results on modifier polymorphisms, minor corrections. 49 pages, 64 reference

Novel Modeling of Combinatorial miRNA Targeting Identifies SNP with Potential Role in Bone Density

MicroRNAs (miRNAs) are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting), a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD) in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential tool for miRNA-related studies. © 2012 Coronnello et al

Pressurized Fluidized-bed Hydroretorting of Eastern Oil Shales Oil Dedusting

This Topical Report on Shale Oil Dedusting'' presents the results of a research program conducted by the Illinois Institute of Technology (IIT, Chicago) to determine the suitability and effectiveness of the lamella electrosettler -- a novel solid-liquid separation device -- for removing fine shale particles from shale oil via the application of an electric field. The work was conducted by IIT from November 1989 through December 1990 as a subcontractor to the Institute of Gas Technology. The overall objective of the larger program was to develop the Pressurized Fluidized-Bed Hydroretorting (PFH) Process for EasternOil Shales.'' The subtask undertaken by IIT was part of a larger task entitled Testing of Process Improvement Concepts.'' The lamella electrosettler has been shown to be an effective method for separating fine particulate (including colloidal) matter from a liquid using the application of an electric field. Using the walls of the settler as electrodes and during continuous operation, solids migrate preferentially toward one of the electrodes and become concentrated in the refuse stream. The product stream is clarified of particulates. The success of the process depends upon the physical properties of the solids and liquids being tested. A sample with a high specific conductance is not suitable for separation in the lamella electrosettler. The liquid begins to heat up under the influence of the electric field and, eventually, may short. Also, under these conditions, the particles cannot maintain a charge. The high conductivity of the shale oil samples tested rendered them unsuitable for further testing in the lamella electrosettler

Pressurized Fluidized-bed Hydroretorting of Eastern Oil Shales Oil Dedusting. Subtask 3.4, Electroseparation of Fines From Shale Oil

This Topical Report on ``Shale Oil Dedusting`` presents the results of a research program conducted by the Illinois Institute of Technology (IIT, Chicago) to determine the suitability and effectiveness of the lamella electrosettler -- a novel solid-liquid separation device -- for removing fine shale particles from shale oil via the application of an electric field. The work was conducted by IIT from November 1989 through December 1990 as a subcontractor to the Institute of Gas Technology. The overall objective of the larger program was to develop the ``Pressurized Fluidized-Bed Hydroretorting (PFH) Process for EasternOil Shales.`` The subtask undertaken by IIT was part of a larger task entitled ``Testing of Process Improvement Concepts.`` The lamella electrosettler has been shown to be an effective method for separating fine particulate (including colloidal) matter from a liquid using the application of an electric field. Using the walls of the settler as electrodes and during continuous operation, solids migrate preferentially toward one of the electrodes and become concentrated in the refuse stream. The product stream is clarified of particulates. The success of the process depends upon the physical properties of the solids and liquids being tested. A sample with a high specific conductance is not suitable for separation in the lamella electrosettler. The liquid begins to heat up under the influence of the electric field and, eventually, may short. Also, under these conditions, the particles cannot maintain a charge. The high conductivity of the shale oil samples tested rendered them unsuitable for further testing in the lamella electrosettler