Stabilization of Enzyme by Exclusive Volume Effect in Hydrophobically Controlled Polymer Microcapsules

Summary: This communication describes an enzyme stabilization method that allows the use of enzymes irrespective of environmental factors, especially heat, while maintaining their activity for a long time. We have designed enzyme microcapsules that consist of papain enzyme cores, poly(propylene glycol) interlayers, and poly(ε‐caprolactone) walls. By confocal laser scanning microscopy measurements and the thermal stability of papain‐loaded microcapsules, it is demonstrated that the papain is surrounded by a hydrophobic polyol layer and stabilized by the exclusive volume effect. In our study, improved thermal stability can be obtained by using more hydrophobic long‐chained polyols, which is understood to be attributed to the effective formation of a hydrophobic polyol layer between the papain and the polymer wall by means of conformational anchoring in the interface.

(A) A CLSM image of a PCL microcapsule containing FITC‐labeled papain and RBITC‐labeled PPG at the same time. (B) A scheme of the role of hydrophobic polyols in the interface of enzyme and polymer.     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Demonstration of Bidirectional Services Using MPEG‐4 BIFS in Terrestrial DMB Systems

Digital broadcasting technology has developed focusing on multi‐channel/multi‐media, high‐definition quality, and mobility‐support. Recently, there has been a clear trend toward bidirectional service with the convergence between broadcasting and communication. The broadcasting viewer is no longer simply a passive receptor but has also become an information generator. Currently, the digital multimedia broadcasting (DMB) specifications are the major standard for portable digital broadcasting and have been establishing the overall guidelines for bidirectional service using the MPEG‐4 system. While detailed specifications for DMB systems are not well‐established for bidirectional service yet, they share the basic concepts underlying the European Eureka‐147 Digital Audio Broadcasting (DAB) system. This paper develops key scenarios for bidirectional service in DMB, describes the signal transaction of broadcasting and return channels, and demonstrates typical scenarios using binary format for scenes (BIFS) in the MPEG‐4 system.     

Correction of a coherent image during KrF excimer laser ablation using a mask projection

Using masks for laser ablation has proven useful in the fabrication of prototypes for the manufacturing of micro-fluidic devices. In this work, an excimer laser was used to engrave microscopic channels on the surface of polyethylene terephthalate (PET), which showed a high absorption ratio for an excimer laser beam with a wavelength of 248 nm. When 50 μm wide rectangular microscopic channels were made using a 500×500 μm square mask and a magnification ratio of 1/10, ditch-shaped defects were found at both corners. The calculation of the laser beam intensity showed that a coherent image in the PET specimen caused the defects. An analysis based on the Fourier diffraction theory enabled the prediction of a coherent shape at the image plane, as well as a diffracted beam between the mask and the image plane. The analysis also showed that the diameter of the aperture was a predominant factor toward the elimination of ditch-shaped defects in the rectangular microscopic channels on the PET produced by an excimer laser ablation.     

Designing-in of quality through axiomatic design

Decisions made during the design stage of product and process development profoundly affect product quality and process productivity. To aid in design decision making, a theoretical framework is advanced; the axiomatic approach to design. Axiomatic design consists of: (1) domains in the design world; (2) mapping between these domains; (3) characterization of a design by a vector in each domain; (4) decomposition of the characteristic vectors into hierarchies through a process of zigzagging between the domains; and (5) the design axioms, viz, independence and information axioms. Statistical process control (SPC) and other methodologies to improve quality are valid only when they are consistent with the independence and information axioms. This paper presents several criteria that govern the design and manufacture of quality products. To be able to control the quality of products, a design must satisfy the independence axiom. Based on this axiom and some theorems, several design criteria are derived and discussed. These criteria provide the bounds for the validity of some of the SPC techniques being used. When there is more than one acceptable design of a product or process, the information axiom must be used to select the best design(s)     

A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

Background  

The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization.     

A Design and Experiment of Speed Controller with PI-Plus Bang-Bang Action for a DC Servomotor with Transistorized PWM Drives

A speed controller with proportional-integral (PI)-plus bang-bang action is proposed for dc servomotors with transistorized pulse width modulated (PWM) drives. The controller employs the PI-action when the magnitude of the error between the reference signal and the speed output signal is smaller than some precribed value. Otherwise, the controller produces the maximum allowable control signal with the integrator reset. Specifically, a mathematical analysis of the motor system with the proposed speed controller is presented and a rule of thumb for parameter design is provided.     

Microencapsulation of cholesteryl alkanoate by polymerization‐induced phase separation and its association with drugs

A new microencapsulation technique is presented in which cholesteryl nonanoate (CN)/poly(methyl methacrylate) (PMMA) microcapsules are produced by the induction of phase separation between CN and PMMA within the droplets during the polymerization. The concentration of CN is the most important factor determining the final morphology of the microcapsules. For example, a polynuclear type is obtained at a low concentration (<20 wt %), a mononuclear type is obtained at a medium concentration (20–30 wt %), and an irregular phase is obtained at a high concentration (>40 wt %). To evaluate the effectiveness of the technique for stabilizing an unstable drug, we selected retinol (vitamin A) as a model drug and loaded it into the CN/PMMA microcapsules. We used a process called solute codiffusion, in which a fine solvent emulsion containing the retinol was diffused uniformly into the CN/PMMA microcapsules. The loading efficiency of retinol was predicted successfully with the aid of a thermodynamic equation. In the thermal stability test of retinol, we found that an effective association with the CN phase was the most important factor determining the limit of its molecular stability. The technique reported in this article has great potential for the microencapsulation of soft materials via a simple process and for the stabilization of unstable drugs. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2202–2213, 2004     

On real hypersurfaces with η-parallel curvature tensor in complex space forms

The purpose of this paper is to give a complete classification of real hypersurfces M in complex space forms M _n(c), c≠0 in terms of an η-parallel curvature tensor and a certain commutative condition defined on the distribution T ₀={X∈T _x M| X⊥ξ} of M in M _n(c).     

Enhanced activity of CuO/ZnO catalyst on the decomposition of dimethylhexane-1,6-dicarbamate into dimethylhexane-1,6-diisocyanate

To decompose dimethylhexane-1,6-dicarbamate (HDC) to hexamethylene diisocyanate (HDI), mixed CuO and ZnO catalysts with Cu/(Cu?+?Zn) ratio of 4 and 8% were prepared by coprecipitation (CP), sequential precipitation (SP) and incipient wetness impregnation (IW). The SP-derived CuO/ZnO catalysts showed higher HDC yields than those derived by CP and IW. The IW method produced CuO/ZnO catalysts consisting of larger CuO and ZnO particles compared to the two precipitation methods. The CP method led to substitution of Zn²⁺ by Cu²⁺ in the hydrozincite precursor phase, resulting in higher BET and Cu surface areas of CuO–ZnO catalysts due to intimate intergrowth of nano-sized particles. However, the inherent character of ZnO in the CP-derived catalysts was modified by interfacial contact between CuO and ZnO identified by UV–visible and Raman spectra. In contrast, the properties of CuO and ZnO, as well as the relatively large surface areas, were kept in the SP-derived catalysts owing to deposition of Cu precipitates to fully aged Zn precipitates. This is believed to be a benefit of the SP method for the reaction. Therefore, our preparation approach has great potential to be extended to various mixed oxide catalysts.