Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD⁺ or O₂. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors.     

Non-invasive and rapid analysis for observation of internal structure of press-coated tablet using X-ray computed tomography

Background: Since the internal structure of a tablet can be measured without destruction of the sample by X‐ray computed tomography (CT), it could be applied to quality control of tablets during the manufacturing process. Aim: A novel, fast, noninvasive tablet observation method was developed to evaluate the internal structure of commercial press-coated tablets by using X-ray CT. Method: Thirty-two CT image slices of four kinds of commercial press-coated tablets (tablets A, B, C, and D) were measured 300 m interval between edges of the tablet by using an X-ray CT. The thinnest layer thickness of the tablets and distance between centers of gravity (DCG) of tables were calculated. Results: The order of the TLT of the tablets was tablet B > tablet C > tablet D > tablet A. The result indicated that the order of DCG was tablet A > tablet D > tablet C > tablet B. Noninvasive observation of the internal structure of commercial, press-coated tablets by X-ray CT has been demonstrated to be useful in quality control of production. Conclusion: The internal structure of press-coated tablets could be observed without pretreatment, without destruction, and very rapidly by X‐ray CT.     

Adaptive backstepping control of wheeled inverted pendulum with velocity estimator

In this paper, we introduce a backstepping control design of a wheeled inverted pendulum. Based on a second-order motion equation of the body angle, an adaptive integral backstepping controller is designed to stabilize the body angle. It is shown that the σ-modification rule in the adaptive update law guarantees the boundedness of the errors in estimating the time-varying signal that is an output of a linear system with every bounded input signal. Then, the stabilizing controller for the wheel angle is constructed by a PD-type positive feedback. The derived controller requires the full-state measurements. In the output feedback case, the K filter or the observer backstepping is needed. However, the structure of the controller becomes complicated. We propose a non-model-based differentiator based on the adaptive update law. Since the non-model-based differentiator does not require any knowledge of the dynamic structure of the signal, we can use it as a velocity estimator for unknown nonlinear systems. Therefore, we replaced the velocity measurement with the estimates by the non-model-based differentiator. Finally, simulation results for the proposed controller are presented.     

Electroelastic Response of Cylindrical Fiber with D∞ Symmetry Exposed to Local Electric Field Through Opposed Electrode Pair

To obtain practical information on the electroelastic behavior of poly-l-lactic acid microtweezers or catheters, a previously constructed analytical technique is used to obtain the electroelastic field solution of a poly-l-lactic acid cylindrical fiber exposed to a local electric field, which is applied through an opposed pair of square-sectioned electrodes. The numerical representation of the solution reveals the detailed field quantity distributions, their importance in the design of microtweezers and catheters, the overall deformation of such devices, and the effects of the electrode dimensions on the deformation.     

Syntheses of Spinon Thermal Conductivity Materials in Sr–Cu–O System by Glass‐Ceramics Technique

We have synthesized spinon thermal conductivity materials in Sr–Cu–O system by glass‐ceramics technique. The materials are promising for active control of thermal energy in microelectronic devices because of high and anisotropic thermal conduction, its controllability, and electric insulation. Nevertheless, research on these materials has been limited to that concerning theoretical perspectives and investigation of physical properties using large single crystals. In this study, we adopt glass‐ceramics technique to synthesize these materials: We prepared melt‐quenched multicomponent oxides including SrO and CuO, and checked its glass‐forming ability and crystallization behaviors by heating. As a result, we have found that SrCuO₂ and Sr₁₄Cu₂₄O₄₁, known as the spinon thermal conductivity materials, are synthesized using SrO–CuO–?Li₂O–?Al₂O₃?–Ga₂O₃ system. This synthesis process for the system will provide practical application of the spinon thermal conductivity materials.     

MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2

Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3′-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects.     

Thermogravimetric behavior of perfluoropolyether

In this article, two kinds of perfluoropolyether (PFPE) with different terminal groups were investigated using thermogravimetric analysis (TGA), infrared (IR) spectroscopy, gel permeation chromatography (GPC), and gas chromatography/gas mass spectrum (GC/MS) analysis. PFPEs with a hydroxyl or carboxylic acid terminal group were more heat stable than was PFPE with carboxylic methyl ester. Perfluoropropylene oxide-type PFPE with a perfluoroethyl terminal group at one end tends to lose weight more rapidly than does copolymer-type PFPE with dihydroxyl or dicarboxyl methyl ester terminal groups at both ends. The residual weight fraction of PFPE with a perfluoroethyl terminal group was dependent on the average molecular weight. The number-average molecular weight of PFPE can be calculated from the peak intensity ratio between the polar group and C F stretching by measuring the IR spectrum of PFPE. The number-average molecular weight of PFPE increased because of the evaporation loss of its low molecular weight fraction and the crosslinking reaction of PFPE with increase in temperature. GC/MS analysis showed that the main product of the pyrolysis of PFPE was hexafluoropylene. We speculated on the PFPE degradation mechanism and the optimum PFPE chemical structure in terms of heat stability. © 1996 John Wiley & Sons, Inc.     

Experimental study of impingement cooling by heat sinks with thin longitudinal fins for LSI packages

This paper reports on the impingement cooling characteristics of a heat sink with thin longitudinal fins of 0.2 mm thickness, which are spaced with a fin-pitch in the range 0.5 mm to 2.0 mm. The air cooling of the heat sink comes from a slot-shaped orifice positioned above the heat-sink center. The breadth of the gap between the fin tops and the inlet orifice is in the range 0 mm to 10 mm. The thermal resistance of the thin longitudinal fins used is about 50% to 57% that of the thick longitudinal fins now in commercial use. The cooling performance of the thin-plate fins is almost the same as that of optimally arranged pin-fins with the same total surface area. A maximum value of six times the heat transfer rate of a single flat plate having the same base area was observed for the thin-plate fins. A comparison of cooling performance between impingement and channel flow systems was conducted. The performance of impingement cooling systems is almost unaffected by the breadth of the gap between the fin tops and the inlet orifice (or, for channel cooling, the upper wall). On the other hand, the performance of channel-cooling systems decreases significantly as the gap widens. © 1997 Scripta Technica, Inc. Heat Trans Jpn Res, 25(7): 449–459, 1996     

Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.