Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree

Objectives: The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes.

Methods: First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10?kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation.

Results: Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors.

Conclusions: This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.     

Removal of dissolved estrogen in sewage effluents by β-cyclodextrin polymer

Substances with estrogenic activity are found in effluents of municipal sewage plants and dairy farms. These effluents have the potential to induce feminization in male fish. In this study, cyclodextrin polymers (CDPs) that are insoluble in both polar and non-polar solvents were selected for the removal of dissolved estrogens in the effluent of a municipal sewage plant. The removal capacity of CDPs was high in the order of β-CDP ≥ γ-CDP ? α-CDP. The mechanism for adsorption of estrogens to β-CDP was not only due to a host-guest interaction as molecular recognition by β-cyclodextrin (β-CD), but also due to adsorption by the polymer matrix. β-CDP of 0.2% (w/v) removed 17β-estradiol (E2) of about 70% from 10⁻¹¹ mol/L, and more than 90% from ≥ 10⁻¹⁰ mol/L. The removal ratios of E2 in the presence of cholesterols, which are contained at higher concentrations than estrogens in sewage effluents and are adsorptive competitor for β-CDP, were about 85% at a cholesterol/E2 molar ratio of 100 and > 90% at molar ratios of 0.1, 1, and 10. The effluent from a municipal sewage plant had estrogenic activity corresponding to 5.5 × 10⁻¹¹ molE2/L by yeast two-hybrid assay. The estrogens in the effluent were also removed > 90% by the β-CDP treatment. Therefore, β-CDP is able to remove dissolved estrogens over a wide range of concentrations in the presence of various contaminants such as wastewaters.     

Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes

Post‐translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing histone tails and controlling their epigenetic modification are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind to histone tails with substantial affinity. We report CA2 and CA3, which exhibited sub‐micromolar affinity to histone tails (especially tails with a trimethylated lysine). Multivalent display of trisulfonated calix[4]arene was important for strong binding. CA2 was applicable not only to synthetic tail peptides but also to endogenous histone proteins, and was successfully used to pull‐down endogenous histones from nuclear extract. These findings indicate the utility of these supramolecular ligands as biochemical tools for studying chromatin regulator protein and as a targeting motif in ligand‐directed catalysis to control epigenetic modifications.     

Real‐time histological imaging of kidneys stained with food dyes using multiphoton microscopy

We have developed a real‐time imaging technique for diagnosis of kidney diseases which is composed of two steps, staining renal cells safely with food dyes and optical sectioning of living renal tissue to obtain histological images by multiphoton microscopy (MPM). Here, we demonstrated that the MPM imaging with food dyes, including erythrosine and indigo carmine, could be used as fluorescent agents to visualize renal functions and structures such as glomerular bloodstreams, glomerular filtration, and morphology of glomeruli and renal tubules. We also showed that the kidneys of IgA nephropathy model‐mice stained with the food dyes presented histopathological characteristics different from those observed in normal kidneys. The use of the food dyes enhances the quality of tissue images obtained by MPM and offers the potential to contribute to a clinical real‐time diagnosis of kidney diseases. Microsc. Res. Tech. 78:847–858, 2015. © 2015 Wiley Periodicals, Inc.     

The role of familiarity in daily well-being: Developmental and cultural variation.

The present study examined life stage and cultural differences in the degree to which familiarity of one's physical location and interaction partner is associated with daily well-being. Participants reported all the activities they engaged in and how they felt during these activities on a previous day using the Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004). Both Korean and American retirees were happier when in a familiar place than in an unfamiliar place, whereas the reverse was true for both Korean and American working adults. In addition, we found cultural differences in the role of familiarity of the interaction partner. Specifically, Koreans (both retirees and working adults) were substantially happier when they interacted with a familiar person than when they interacted with an unfamiliar person. In contrast, Americans (both retirees and working adults) were no happier with a familiar person than with an unfamiliar person. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Giant electric double-layer capacitance of heavily boron-doped diamond electrode

The physical and electrochemical properties of boron-doped polycrystalline diamond electrodes, prepared with various B/C ratio, i.e., 0.1%, 0.5% (BDD-A), 1% (BDD-B), and 5% (BDD-C), were investigated. Electrochemical measurements of the heavily boron-doped films (BDD-C) showed giant electric double-layer capacitance and activity which is significantly larger than BDD-A and BDD-B as well as glassy carbon electrodes. However, interestingly, actual boron concentration of BDD-C was observed to be almost the same as that of BDD-B by secondary ion mass spectroscopy (SIMS) and glow discharge optical emission spectroscopy (GDOES) analysis. It is suggested that the large capacitance is due to a few sp²-bonded carbon impurities, which was observed only in BDD-C, although the amount of the sp²-bonded nondiamond species are very small. In the present work, the reason for the interesting electrochemical properties of heavily boron-doped diamond electrodes is discussed. Furthermore, dimensional stability of the electrodes was also confirmed by conducting harsh anodic treatment.     

Evaluation of cost reduction potential for 1 kW class SOFC stack production: Implications for SOFC technology scenario

Recently, a commercial version of a residential solid oxide fuel cell (SOFC) system with a flat tubular cell has been developed. However, the system cost still remains very high, which is a barrier to its widespread use. In this study, the potential for cost reductions in SOFC stack production was investigated in order to contribute to the viability of the widespread use of such residential SOFC systems in future. A cost analysis of 700 W SOFC stack production based on a process integration modeling was conducted. The present bottom–up approach enabled us to perform a sensitivity analysis with a variety of parameters in terms of cell design, the production process and cell performance. This allowed us to investigate the effects of these factors on the production cost, thereby revealing the quantitative impact of each technological improvement on the cost reduction potential. The present analysis also revealed innovation pathways which could result in technology scenarios where residential SOFC systems could reach a break-even point in comparison with the baseload electricity cost. The analysis of the cost reduction potential presented here provides a useful viewpoint for developing a research strategy for state-of-the-art SOFC technology.