Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Electro-Thermal model of thermal breakdown in multilayered dielectric elastomers

Energy transduction of dielectric elastomers involves minute electrical and mechanical losses, both of which potentially increase the temperature within the elastomer. Thermal breakdown of dielectric elastomers occur when heat generated therein cannot be balanced by heat loss on the surface, which is more likely to occur in stacked dielectric elastomers. In this article an electro-thermal model of a multilayered dielectric elastomer able to predict the possible number of layers in a stack before thermal breakdown occurs is presented. Simulation results show that point of breakdown is greatly affected by an increase in surrounding temperature and applied electric field. Furthermore, if the stack diameter is large, thermal insulation of the cylindrical surface is a valid approximation. Two different expressions for the electrical conductivity are used, and it is concluded that the Frank-Kamenetskii expression is more conservative in prediction of point of breakdown than the Arrhenius expression, except at high surrounding temperature. © 2018 American Institute of Chemical Engineers AIChE J, 65: 859–864, 2019     

A framework for improving the efficiency of operational testing through Bayesian adaptive design

When developing a product, it is important to consider product performance from a user perspective. This type of evaluation can be done through operational testing—assessing the ability of representative users to satisfactorily accomplish tasks with the product in operationally representative environments. This process can be expensive and time-consuming, but is critical to understanding whether the product can adequately do the job for which it was designed. We show how an existing design of experiments (DOEs) process for operational testing can be leveraged to construct a Bayesian adaptive design. This design, nested within the larger design created by the DOE process, allows interim analyses to stop testing early for success or futility. Representative simulations are presented to demonstrate how these interim analyses can be used in an operational test setting, and reductions in necessary test events are shown. The application of Bayesian-adaptive design methods will allow future operational testing to be conducted in less time and at less expense, on average, without compromising the ability of the existing process to verify the product meets the user's needs.     

Electro-thermal and -mechanical model of thermal breakdown in multilayered dielectric elastomers

Multiple breakdown phenomena may take place when operating dielectric elastomers. Thermal breakdown, which occurs due to Joule heating, becomes of special importance when using multilayered stacks of dielectric elastomers, due to the large volume-to-surface-area-ratio. In this article, a 2D axisymmetric finite-element model of a multilayered stack of dielectric elastomers is set up in COMSOL Multiphysics®. Both the electro-thermal and electro-mechanical couplings are considered, allowing for determination of the onset of thermal breakdown. Simulation results show that an entrapped particle in the dielectric elastomer drastically reduces the possible number of layers in the stack. Furthermore, the possible number of layers is greatly affected by the ambient temperature and the applied voltage. The performance of three hyperelastic material models for modeling the elastomer deformation are compared, and it is established that the Gent model yields the most restrictive prediction of breakdown point, while the Ogden model yields the least restrictive estimation.     

PAHs in sediments of the Black River and the Ashtabula River, Ohio: source apportionment by factor analysis

Sources of polycyclic aromatic hydrocarbons (PAHs) in the Black River and Ashtabula River sediments were apportioned using a factor analysis (FA) model with nonnegative constraints. Source profiles, contributions (microg/g) and percent contributions are determined with no prior knowledge of sources. The FA model includes scaling and backscaling of data with average PAH concentrations, without sample normalization. The present work is a follow-up to studies that used a chemical mass balance model to apportion sources to the same data sets. Literature source profiles, modified based on gas/particle partitioning of individual PAHs, from nine PAH sources were considered for comparison. FA results for a three-source solution indicate traffic (58%), coke oven (26%), and wood burning/coal tar (16%) are the primary PAH sources to Black River sediments. The primary PAH sources to the Ashtabula River sediments are traffic (51%), coke oven (44%), and wood burning (5%). This work supports the previous studies of Black River and Ashtabula River PAHs by CMB model. In addition, FA provides a more realistic fit to Ashtabula River model data by eliminating 100% contributions from one source.     

Gravity drainage of activated sludge: new experimental method and considerations of settling velocity, specific cake resistance and cake compressibility

A laboratory scale setup was used for characterization of gravitational drainage of waste activated sludge. The aim of the study was to assess how time of drainage and cake dry matter depended on volumetric load, SS content and sludge floc properties. It was demonstrated that activated sludge forms compressible cakes, even at the low pressures found in gravitational drainage. The values of specific cake resistance were two to three orders of magnitude lower than those obtained in pressure filtration. Despite the compressible nature of sludge, key macroscopic parameters such as time of drainage and cake solid content showed simple functional dependency of the volumetric load and SS of a given sludge. This suggests that the proposed method may be applied for design purposes without the use of extensive numerical modeling. The possibilities for application of this new technique are, among others, the estimation of sludge drainability prior to mechanical dewatering on a belt filter, or the application of surplus sludge on reed beds, as well as adjustments of sludge loading, concentration or sludge pre-treatment in order to optimize the drainage process.     

Object–Oriented Enterprise Modeling and Simulation of AEC Projects

In this paper we describe an object–oriented framework for developing enterprise models of Architecture, Engineering, Construction projects, and a methodology for formalizing these models such that they can be used for discrete event simulation of information processing and coordination in project execution. The simulation results can be used to predict the probable effects of carrying out proposed changes in planning and managing projects.
In our enterprise modeling framework we represent engineering design projects in terms of deliverables (requirements and solutions), plans (activities and process relations), and organization (participants and organizational relations). The resulting project model is the starting point for identifying coordination requirements between project team participants. Our methodology uses matrix techniques derived from qualtiy function deployment (QFD) to identify interactions between project requirements and solutions and calculate measures of product complexity . We then describe information flow between project activities in a similar matrix and calculate measures of process uncertainty . Finally, we identify the responsibilities of project team members and use a matrix to point out organizational interdependencies .
We apply our framework and methodology to model and simulate engineering design for a major extension of an electrical power substation. Our simulation results demonstrate how project performance is contingent on the fit between the project policies and the objectives and preferences of the project team.