Latent structure modeling underlying theophylline tablet formulations using a Bayesian network based on a self-organizing map clustering

The “quality by design” concept in pharmaceutical formulation development requires the establishment of a science-based rationale and design space. In this article, we integrate thin-plate spline (TPS) interpolation, Kohonen’s self-organizing map (SOM) and a Bayesian network (BN) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared using a standard formulation. We measured the tensile strength and disintegration time as response variables and the compressibility, cohesion and dispersibility of the pretableting blend as latent variables. We predicted these variables quantitatively using nonlinear TPS, generated a large amount of data on pretableting blends and tablets and clustered these data into several clusters using a SOM. Our results show that we are able to predict the experimental values of the latent and response variables with a high degree of accuracy and are able to classify the tablet data into several distinct clusters. In addition, to visualize the latent structure between the causal and latent factors and the response variables, we applied a BN method to the SOM clustering results. We found that despite having inserted latent variables between the causal factors and response variables, their relation is equivalent to the results for the SOM clustering, and thus we are able to explain the underlying latent structure. Consequently, this technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulation.     

Detailed analyses of key phenomena in core disruptive accidents of sodium-cooled fast reactors by the COMPASS code

A five-year research project has been initiated in 2005 to develop a code based on the MPS (Moving Particle Semi-implicit) method for detailed analysis of key phenomena in core disruptive accidents (CDAs) of sodium-cooled fast reactors (SFRs). The code is named COMPASS (Computer Code with Moving Particle Semi-implicit for Reactor Safety Analysis). The key phenomena include (1) fuel pin failure and disruption, (2) molten pool boiling, (3) melt freezing and blockage formation, (4) duct wall failure, (5) low-energy disruptive core motion, (6) debris-bed coolability, and (7) metal–fuel pin failure. Validation study of COMPASS is progressing for these key phenomena. In this paper, recent COMPASS results of detailed analyses for the several key phenomena are summarized. Simulations of GEYSER and THEFIS experiments were performed for dispersion and freezing behaviors of molten materials in narrow flow channels. In particular, the latter experiment using melt–solid mixture is also related to fundamental behavior of low energy disruptive core. CABRI-TPA2 experiment was simulated for boiling behavior of molten core pool. Expected mechanism of heat transfer between molten fuel and steel mixture was reproduced by the simulation. Analyses of structural dynamics using elastoplastic mechanics and fracture criteria were performed for SCARABEE BE+3 and CABRI E7 experiments. These two analyses are especially focused on thermal and mechanical failure of steel duct wall and fuel pin, respectively. The present results demonstrate COMPASS will be useful to understand and clarify the key phenomena of CDAs in SFRs in details.     

Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.     

Dual-plasma ion process for surface treatment of insulators

Surface treatment of insulator materials has growing needs recently. However, accumulation of charges on the insulator surface limits the applicability of plasma methods for the insulator processing. A radio-frequency-bias method is a good choice but it still has a problem coming from the oscillating sheath potential. In the present study, we are proposing the dual-plasma ion process, a new plasma process that enables for insulator samples to be treated by an energy-controlled, dc ion beam without surface charging. The concept and results of the proof-of-principle experiment are given.     

Contrasting Lubrication Properties of Imidazolium-Based Ionic Liquids Affected by the Nature of the Surface Under High Vacuum

The lubrication performance of imidazolium-based ionic liquids was evaluated under high vacuum using a ball-on-disk tribometer. A ball and a flat disk made of SUS440C stainless steel were used as specimens. A surface of the as-received flat disk specimen was covered with a thick oxide layer (>40 nm). For an examination of the effect of the surface oxide layer on the tribological performance of the ionic liquids under high vacuum, another specimen with a thin oxide layer (approx. 4 nm thick) was prepared. The ionic liquids with the TFSA anion showed better lubrication performance with the thicker oxide layer specimen, whereas the ionic liquids with the BF4 anion showed superior performance with the thinner oxide layer specimen. These results are discussed based on the HSAB principle. It is shown that the mechanism of the opposite tribological characteristics can be reasonably explained in terms of the chemical hardness by the HSAB principle.     

Development of a Time–Intensity Evaluation System for Consumers: Measuring Bitterness and Retronasal Aroma of Coffee Beverages in 106 Untrained Panelists

In order to develop products that are acceptable to consumers, it is necessary to incorporate consumers’ intentions into products’ characteristics. Therefore, investigation of consumers’ perceptions of the taste or smell of common beverages provides information that should be useful in predicting market responses. In this study, we sought to develop a time–intensity evaluation system for consumer panels. Using our system, we performed time–intensity evaluation of flavor attributes (bitterness and retronasal aroma) that consumers perceived after swallowing a coffee beverage. Additionally, we developed quantitative evaluation methods for determining whether consumer panelists can properly perform time–intensity evaluation. In every trial, we fitted an exponential function to measured intensity data for bitterness and retronasal aroma. The correlation coefficients between measured time–intensity data and the fitted exponential curves were greater than 0.8 in about 90% of trials, indicating that we had successfully developed a time–intensity system for use with consumer panelists, even after just a single training trial using a nontrained consumer. We classified participants into two groups based on their consumption of canned coffee beverages. Significant difference was observed in only AUC of sensory modality (bitterness compared with retronasal aroma) among conventional TI parameters using two‐way ANOVA. However, three‐way ANOVA including a time course revealed significant difference between bitterness and retronasal aroma in the high‐consumption group. Moreover, the high‐consumption group more easily discriminated between bitterness and retronasal aroma than the low‐consumption group. This finding implied that manufacturers should select consumer panelists who are suitable for their concepts of new products.     

Electrocatalytic activity of amorphous RuO2 electrode for oxygen evolution in an aqueous solution

The electrocatalytic activity of amorphous and crystalline RuO₂ thin films for oxygen evolution in an aqueous solution was investigated. The RuO₂ films were prepared on FTO substrates by electrodeposition or RF magnetron sputtering technique. The obtained films were annealed at various temperatures. In both cases, the as-prepared films or the 200 °C annealed film had an amorphous structure, whereas the films annealed at 300 °C and over were crystallized to rutile structure. The analysis of the Tafel slope indicated that the rate-determining step in the oxygen evolution reaction on the amorphous RuO₂ was the combination of the adjacent Ru–OH groups, whereas that on crystalline RuO₂ was the dissociation of O–H bond in Ru–OH group. The onset potentials of the amorphous RuO₂ films for oxygen evolution were shifted toward the negative side by 0.06–0.03 V from those for the rutile crystalline samples. The shift of the onset potential is probably attributed to the structural flexibility which is characteristic of the amorphous surface. This result suggested that the electrocatalytic activity of amorphous RuO₂ for oxygen evolution was higher than that of rutile crystalline RuO₂.