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.     

Rationally Designed Polypharmacology: α-Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl-1 and HDM2

Protein–protein interactions (PPIs), many of which are dominated by α-helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl-2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl-2 pro-life proteins, such as Mcl-1, and pro-death proteins, such as Bim, regulate the intrinsic pathway of apoptosis. p53, a tumor-suppressor protein, also has a pivotal role in apoptosis and is negatively regulated by its E3 ubiquitin ligase HDM2. Both Mcl-1 and HDM2 are upregulated in numerous cancers, and, interestingly, there is crosstalk between both protein pathways. Recently, synergy has been observed between Mcl-1 and HDM2 inhibitors. Towards the development of new anticancer drugs, we herein describe a polypharmacology approach for the dual inhibition of Mcl-1 and HDM2 by employing three densely functionalized isoxazoles, pyrazoles, and thiazoles as mimetics of key α-helical domains of their partner proteins.     

Modeling the influence of changes in aliphatic structure on char surface area during coal pyrolysis

The influence of changes in aliphatic structure on char surface area during coal pyrolysis was modeled, and the effect was introduced to a previous char surface area model for lignite pyrolysis established based on the chemical percolation devolatilization (CPD) model. The modified model can predict not only the N₂ and CO₂ char surface area during rapid pyrolysis of three lignites but also the CO₂ char surface area of two high-volatile bituminous coals; the agreement of the modified model with experiments is improved at high temperatures. The decrease in aliphatic chain length can reduce adsorption positions around aromatic core, and decrease char surface area. When mass release is more than 55% at about 1,100 K, the predicted N₂ char surface area starts to decrease with further generation of volatiles, and the increase of predicted CO₂ char surface area with increasing generation of volatiles also become slow at the end of mass release.     

The chemistry of heavy metals in digested sewage sludge—II. Heavy metal complexation with soluble organic matter

Characterisitcs of copper-binding, in the soluble fraction of a digested sewage sludge, were determined using ion-selective electrodes. Results showed that ion exchange with protons is a principal component in copper binding and that the soluble organic matter has a cation exchange capacity of 8.86 m-equiv g⁻¹ at pH 6.5. A pH-dependent exchange constant, defined in terms of mole fractions of exchange components, describes the data in the pH range 2–8 and is independent of both pH and the extent of exchange in the range 5.5–8. Supplementary data include acid/base titration curves and simple kinetic measurements. Anion uptake is insignificant in the pH range 2.5–7. A model of the aqueous phase of a sewage sludge, containing soluble organic matter with only copper and protons as competing ions, predicts that at pH 7 over 99% of the copper present will be bound to the soluble organic matter.     

The cost of a package plant membrane bioreactor

The capital and operating costs associated with a small package plant MBR for small-scale domestic duty has been appraised based on a medium-strength municipal wastewater. The three main membrane configurations were considered, these being multi-tube, hollow fibre and flat sheet, with the most appropriate plant design chosen for each configuration. The analysis proceeded via a consideration of the estimated amortised capital costs of the plant individual components and their installation, coupled with operating costs based largely on energy demand and residuals management. Energy demand was calculated from aeration and pumping costs, with aeration based on a combination of empirical relationships for membrane aeration and mass balance, and the modified Activated Sludge Model version 2 used for estimating tank size and sludge generation. Results indicate that it is possible to produce a single household MBR at a capital cost similar to the current market cost for package treatment plants. Desludging and maintenance of these plants is similar but power requirements for an MBR are around 4 times that associated with more conventional package plants. Economies of scale exist from 6-20 p.e. plants but above 20 p.e. there is little cost difference per head, due to the design assumptions made. CAPEX and OPEX are to some extent interchangeable; reductions in CAPEX are associated with an increase in OPEX and vice versa. Whilst costs are high, the market for package MBRs is significantly influenced by the recycling potential of the effluent produced.     

Ventilation of small factory units

Ventilation rates have been measured using tracer gas techniques in a number of modern factory units with no mechanical ventilation. Wind direction remained fairly constant throughout the tests on individual units, enabling the variation of ventilation rate with wind speed to be determined. In the second phase of the work, measurements were made on a single building under a wide range of weather conditions. Although no correlation with wind direction was apparent, it was shown that the ventilation rate varied not only with wind speed, but also with the difference between the internal and external temperatures, i.e. the “stack effect”.     

Enclothed cognition and hidden meanings in important Ottoman textiles

This paper illustrates how hidden details in garment design may reveal important clues about the motives of the wearer or designer that are of considerable cultural relevance. We suggest these hidden design features may reflect key psychological factors previously not considered. We illustrate this by doing a multilevel analysis of two important sixteenth century examples of Ottoman court clothing from the Topkapi Palace Museum. We show that these garments contain early examples of the use of “enclothed cognition” where the designs themselves are likely to have influenced the mind of the wearer. We suggest that the historical-social analysis of clothing may benefit from considering the concealed, as well as the explicit, psychologically relevant design features. We suggest that psychosocial interpretations of clothing may help further our understanding of textile and apparel design more generally, even within an historical context.