Synthetic diamond electrodes: The effect of surface microroughnesson the electrochemical properties of CVD diamond thin films on titanium

The electrochemical behavior of B-doped diamond films on Ti substrates subjected to different pretreatment procedures (annealing, sand-blasting, and etching in HCl) is evaluated as a function of surface microroughness. Generally, the differential capacitance follows the true surface area of the electrodes. The width of the potential window also increases, but slightly, with the roughness. The electrode reversibility in the [Fe(CN)₆]³⁻/[Fe(CN)₆]⁴⁻ redox system increases with increasing surface roughness. The apparent increase in the reversibility of the reaction may be also explained by the decrease in the true current density. Although the variations in the electrochemical parameters are not strongly pronounced, the tendencies observed can be used to optimise the electrode properties.     

Curing reaction of amino‐terminated aqueous‐based polyurethane dispersions with triglycidyl‐containing compound

Amino‐terminated anionic aqueous‐based polyurethane (PU) dispersion was obtained from NCO‐terminated PU prepolymer, which was neutralized with an excess triethylamine (TEA) and chain extended by ethylenediamine (EDA) during water dispersion process. That PU prepolymer was obtained from a polyaddition reaction of isophorone diisocyanate (IPDI), polypropylene glycol‐2000 (PPG‐2000), and 2,2′‐dimethylol propanoic acid (DMPA). This aqueous‐based PU dispersion was treated with trimethylolpropane triglycidyl ether (TMPTGE) as a latent curing agent and resulted in a self‐cured PU resin on drying. A model ring‐opening curing reaction between oxirane group of TMPTGE with terminal amino group of PU was demonstrated by glycidol with n‐butyl amine. The physical and mechanical properties as well as thermogravimetric analyses of these self‐cured PU resins were evaluated in this article. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection

More than 170 million people worldwide are affected by the hepatitis C virus (HCV). The disease has been described as a "silent epidemic" and "a serious global health crisis". HCV infection is a leading cause of chronic liver disease such as cirrhosis, carcinoma, or liver failure. The current pegylated interferon and ribavirin combination therapy is effective in only 50% of patients. Its moderate efficacy and apparent side effects underscore the need for safer and more effective treatments. The nonstructural NS3 protease of the virus plays a vital role in the replication of the HCV virus. The development of small molecule inhibitors of NS3 protease as antiviral agents has been intensively pursued as a viable strategy to eradicate HCV infection. However, it is a daunting task. The protease has a shallow and solvent-exposed substrate binding region, and the inhibitor binding energy is mainly derived from weak lipophilic and electrostatic interactions. Moreover, lack of a robust in vitro cell culture system and the absence of a convenient small animal model have hampered the assessment of both in vitro and in vivo efficacy of any antiviral compounds. Despite the tremendous challenges, with access to a recently developed cell-based replicon system, major progress has been made toward a more effective small molecule HCV drug. In our HCV program, facing no leads from our screening effort, a structure-based drug design approach was carried out. An alpha-ketoamide-type electrofile was designed to trap the serine hydroxyl of the protease. Early ketoamide inhibitors mimicked the structures of the peptide substrates. With the aid of X-ray structures, we successfully truncated the undecapeptide lead that had a molecular weight of 1265 Da stepwise to a tripeptide with a molecular weight of 500 Da. In an attempt to depeptidize the inhibitors, various strategies such as hydrazine urea replacement of amide bonds and P2 to P4 and P1 to P3 macrocyclizations were examined. Further optimization of the tripeptide inhibitors led to the identification of the best moieties for each site: primary ketoamide at P', cyclobutylalanine at P1, gem-dimethylcyclopropylproline at P2, tert-leucine at P3, and tert-butyl urea as capping agent. The combination of these led to the discovery of compound 8 (SCH 503034, boceprevir), our clinical candidate. It is a potent inhibitor in both enzyme assay (Ki* = 14 nM) and cell-based replicon assay (EC 90 = 0.35 microM). It is highly selective (2200x) against human neutrophil elastase (HNE). Boceprevir is well tolerated in humans and demonstrated antiviral activity in phase I clinical trials. It is currently in phase II trials. This Account details the complexity and challenges encountered in the drug discovery process.     

Hybridization of aqueous PU/epoxy resin via a dual self‐curing process

Amino‐terminated and carboxyl‐containing polyurethane (PU) is prepared by an isocyanate‐terminated PU prepolymer process. Carboxyl‐containing epoxy resin is obtained from a half‐esterification of epoxy resin with maleic anhydride. These two aqueous resins are obtained after neutralization with triethylamine and dispersion into water phase, respectively. A latent curing agent (TMPTA‐AZ) is prepared by a Michael addition of aziridine with trimethylolpropane triacrylate (TMPTA). A self‐curing system of PU/epoxy hybrid is obtained from a blending of these two aqueous resins with latent curing agent. PU/epoxy hybrid is derived from two self‐curing reactions on drying. The first curing for hybridization between PU amino groups with oxirane groups of epoxy resin is via a ring‐opening reaction and the secondary curing takes place on carboxyl groups of PU/epoxy hybrid with aziridine of TMPTA‐AZ. The final properties of these dual self‐cured PU/epoxy hybrids are reported. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A novel cross-coupling control design for Bi-axis motion

A new structure of cross-coupling controller for precise tracking in motion control is proposed in this paper. When compared with the conventional cross-coupling system, this new structure has the advantage that the compensators in CCC have a simpler design process than conventional ones and so does its stability analysis. The proposed compensator (or controller) is evaluated and compared experimentally with a traditional uncoupled controller on a microcomputer controlled dual-axis positioning system. The experimental results show that the new structure of cross-coupling controller remarkably reduces contour error. In addition, this new controller can be implemented easily on a majority of motion systems in use today via reprogramming the reference position command subroutine.     

In Vitro Characterization of Neutralizing Hen Antibodies to Coxsackievirus A16

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Children aged <5 years are the most affected by CA16 HFMD globally. Although clinical symptoms of CA16 infections are usually mild, severe complications, such as aseptic meningitis or even death, have been recorded. Currently, no vaccine or antiviral therapy for CA16 infection exists. Single-chain variable fragment (scFv) antibodies significantly inhibit viral infection and could be a potential treatment for controlling the infection. In this study, scFv phage display libraries were constructed from splenocytes of a laying hen immunized with CA16-infected lysate. The pComb3X vector containing the scFv genes was introduced into ER2738 Escherichia coli and rescued by helper phages to express scFv molecules. After screening with five cycles of bio-panning, an effective scFv antibody showing favorable binding activity to proteins in CA16-infected lysate on ELISA plates was selected. Importantly, the selected scFv clone showed a neutralizing capability against the CA16 virus and cross-reacted with viral proteins in EV71-infected lysate. Intriguingly, polyclonal IgY antibody not only showed binding specificity against proteins in CA16-infected lysate but also showed significant neutralization activities. Nevertheless, IgY-binding protein did not cross-react with proteins in EV71-infected lysate. These results suggest that the IgY- and scFv-binding protein antibodies provide protection against CA16 viral infection in in vitro assays and may be potential candidates for treating CA16 infection in vulnerable young children.     

Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

Resveratrol can affect the physiology or biochemistry of offspring in the maternal–fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4–8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut–liver axis in the offspring.     

Electrochemical pitting behaviour of type 321 stainless steel in sulfide-containing chloride solutions

The pitting behaviour of type 321 stainless steel in sulfide-containing chloride aqueous environments was studied using cyclic potentiodynamic polarization. A well-established correlation between H₂S and Na₂S₂O₃ in the study of corrosion was applied, that is, H₂S was simulated by Na₂S₂O₃. The major factors affecting the pitting corrosion of type 321 stainless steel are the Cl^- concentration, solution pH and temperature. The results clearly indicate that both E_pit and E _pp decrease with increasing Cl^- concentration and temperature, while I _pass is more sensitive to temperature variation. E _pit decreased with decreasing pH in the range 2 < pH < 7.5. The surface morphology and chemistry of the corroded type 321 stainless steel resulting from anodic polarization in 0.01 M S₂O ₃ ^2- -containing Cl^- solution were analysed by XRD, SEM and EPMA. A higher concentration of sulfur was found in the pits, and the dark surface film was mainly composed of FeS and -Fe₂O₃. The results describe the pitting behaviour of type 321 stainless steel in sulfide-containing Cl^- aqueous environments.     

Design,fabrication and performance analysis of a 200 W PEM fuel cell short stack

A PEM fuel cell short stack of 200 W capacity, with an active area of 100 cm² has been designed and fabricated in-house. The status of unit cell performance was 0.55 W cm⁻². Based on the unit cell technology, a short stack has been developed. The proper design of uniform flow distribution, cooling plate and compressed end plate were important to achieve the best performance of the short stack. The performance of four cells stack was analyzed in static and dynamic modes. In the static mode of polarization curve, the stack has peak power density of 0.55 W cm⁻² (220 W) at 0.5 V per cell, when the voltage was scanning from low to high voltage (1.5–3.5 V), and resulted in minimum water flooding inside the stack. In this study a series of dynamic loadings were tested to simulate the vehicle acceleration. The fuel cell performances respond to dynamic loading influenced by the hydrogen/air stoichiometric, back pressure, and dynamic-loading time. It was needed high hydrogen stoichiometric and back pressure to maintain high dynamic performance. In the long-time stable power testing, the stack was difficult to maintain at high performance, due to the water flooding at high output power. An adjusting cathode back-pressure method for purging water was proposed to prevent the water flooding at flow channels and maintain the stable output power at 170 W (0.42 W cm⁻²).     

Room temperature transport measurements on Bridgman-grown p-type CuIn1−xGaxSe2

Room temperature measurements were made of electrical conductivity (σ), Hall coefficient (R_H) and Seebeck coefficient (α) on filamentary samples of p-type CuInSe₂ and CuIn_1−xGa_xSe₂ with x0.3, cut from vertically grown Bridgman ingots. Analysis of the results was done on a two-carrier basis, due to the higher ratio of electron to hole mobility (b) in these materials compared to elemental semiconductors. This treatment yielded a preferred b-value of 5 and to lower calculated hole concentrations than (R_He)⁻¹ and higher hole mobilities than R_Hσ, based on a one-carrier interpretation. This effect was particularly marked in p-type samples with a hole concentration below 10¹⁷ cm⁻³, where even a few percent of minority electrons can play an important role.