Quantitation and pharmacokinetics of 1,4‐diamino‐2,3‐dicyano‐1,4‐bis (2‐aminophenylthio) butadiene (U0126) in rat plasma by liquid chromatography‐tandem mass spectrometry

A simple, robust, and rapid LC‐MS/MS method was developed for the quantitation of U0126 and validated in rat plasma. Plasma samples (20 μL) were deproteinized using 200 μL ACN containing 30 ng/mL of chlorpropamide, internal standard. Chromatographic separation performed on an Agilent Poroshell 120 EC‐C₁₈ column (4.6 × 50 mm, 2.7 μm particle size) with an isocratic mobile phase consisting of a 70:30 v/v mixture of ACN and 0.1% aqueous formic acid. Each sample was run at 0.6 mL/min for a total run time of 2 min per sample. Detection and quantification were performed using a mass spectrometer in selected reaction‐monitoring mode with positive ESI at m/z 381 → 123.9 for U0126 and m/z 277 → 175 for the internal standard. The standard curve was linear over a concentration range of 20–5000 ng/mL with correlation coefficients greater than 0.9965. Precision, both intra‐ and interday, was less than 10.1% with an accuracy of 90.7–99.4%. No matrix effects were observed. U0126 in rat plasma degraded approximately 41.3% after 3‐h storage at room temperature. To prevent degradation, sample handling should be on an ice bath and all solutions kept at 4°C. This method was successfully applied to a pharmacokinetic study of U0126 at various doses in rats.     

Hydrogen exchange study on the hydroxyl groups of serine and threonine residues in proteins and structure refinement using NOE restraints with polar side-chain groups

We recently developed new NMR methods for monitoring the hydrogen exchange rates of tyrosine hydroxyl (Tyr-OH) and cysteine sulfhydryl (Cys-SH) groups in proteins. These methods facilitate the identification of slowly exchanging polar side-chain protons in proteins, which serve as sources of NOE restraints for protein structure refinement. Here, we have extended the methods for monitoring the hydrogen exchange rates of the OH groups of serine (Ser) and threonine (Thr) residues in an 18.2 kDa protein, EPPIb, and thus demonstrated the usefulness of NOE restraints with slowly exchanging OH protons for refining the protein structure. The slowly exchanging Ser/Thr-OH groups were readily identified by monitoring the (13)C(β)-NMR signals in an H(2)O/D(2)O (1:1) mixture, for the protein containing Ser/Thr residues with (13)C, (2)H-double labels at their β carbons. Under these circumstances, the OH groups exist in equilibrium between the protonated and deuterated isotopomers, and the (13)C(β) peaks of the two species are resolved when their exchange rate is slower than the time scale of the isotope shift effect. In the case of EPPIb dissolved in 50 mM sodium phosphate buffer (pH 7.5) at 40 °C, one Ser and four Thr residues were found to have slowly exchanging hydroxyl groups (k(ex) < ~40 s(-1)). With the information for the slowly exchanging Ser/Thr-OH groups in hand, we could collect additional NOE restraints for EPPIb, thereby making a unique and important contribution toward defining the spatial positions of the OH protons, and thus the hydrogen-bonding acceptor atoms.     

Structural feature of bent DNA recognized by HMGB1

High Mobility Group Box 1 (HMGB1) protein, a potential therapeutic target, binds bent DNAs structure-specifically. Here we report on a crucial structural feature of the bent DNA required for strong binding to HMGB1. NMR structures of two bent DNA oligomers, only one of which binds strongly to HMGB1, revealed that the presence of a pocket structure on the minor groove is crucial for strong binding through penetration of a phenylalanine residue.     

Determination of <Superscript>3</Superscript>H and <Superscript>14</Superscript>C in the Dry Active Wastes (DAW) generated from the Light Water Reactors (LWR) by a wet oxidation method

³H and ¹⁴C Measurements of the dry active waste (DAW), such as the cotton, paper, and vinyl, generated from a nuclear power plant (NPP) were conducted with wet oxidation using open vessel equipment based on simulation results. The recovery efficiency with the simulated samples was around 93% with a relative standard deviation (RSD) of 1–3%. A liquid scintillation counter (LSC) was used for counting and adjusted to a quenching correction curve. The counting value was evaluated for the minimum detectable activity (MDA), which was found to be about 4 × 10⁻¹ Bq/g for ³H and 2 × 10⁻² for ¹⁴C when approximately 5 g of the samples were measured. The measured DAW samples for the cotton, paper, and vinyl generated from NPP achieved of RSD values of 25, 25, and 60%, respectively, for ³H and 0–50% for ¹⁴C.     

PVA nano composite membrane for DMFC application

A new PEM composite membrane comprising of polyvinyl alcohol (PVA), sulfonic acid functionalized CNT and fluorinated MMT has been fabricated. Composite polymer membrane has been prepared by simple solution casting method. Composite properties have been evaluated by using thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), and FTIR techniques. The proton conductivity, methanol crossover and water uptake properties of newly fabricated membrane have been studied. The polymer membrane shows good thermal properties. The water content is in the range of 35-45%. Especially, it has been found that the fluorinated MMT used in this study plays a decisive role in water uptake and acts as a hydrophobic surface for controlling the swelling. The proton conductivities and the methanol permeabilities of all the membranes are in the range of 10^− 3 to 10^− 2 S/cm and 2.08 × 10^− 6 cm²/s at room temperature, respectively.     

Gold nanoparticles with cyclic phenylazomethines: one-pot synthesis and metal ion sensing

New gold nanoparticles covered with cyclic phenylazomethine (CPA) were obtained by a one-pot synthesis. It is confirmed by XPS that imines of CPA in the nanoparticles (Au-CPA) are partially reduced to amines. The amine part of CPA in Au-CPA is attached to the surfaces of gold nanoparticles, and the imine part works as a redox-active site. A glassy carbon electrode modified with Au-CPA was revealed to work as an electrochemical probe for metal ion sensing.     

The changes of assessment at middle school level in Korea

Mathematics education in Korea is currently in a period of transition. The new national curriculum standard was released in 2009 and will be implemented by middle schools in 2013. Korean education has evolved from merely assessing students’ knowledge to figuring out their mathematical process using various assessment methods. The purpose of the national level assessment has been expanded to measure individual achievement. The assessment framework also has changed not only to focus on the content domain but to include the behavior domain as well. However, there were some difficulties in assessing the students’ solving process, including trying to implement various assessment methods in the classrooms. This paper aims to examine the development of assessment and to provide direction for the future application of assessment to the new Korean curriculum by analyzing middle school students’ assessment result at the national level and the class level in the changing era.     

Brain tumor diagnostic model and dietary effect based on extracellular vesicle microbiome data in serum

The human microbiome has been recently associated with human health and disease. Brain tumors (BTs) are a particularly difficult condition to directly link to the microbiome, as microorganisms cannot generally cross the blood–brain barrier (BBB). However, some nanosized extracellular vesicles (EVs) released from microorganisms can cross the BBB and enter the brain. Therefore, we conducted metagenomic analysis of microbial EVs in both serum (152 BT patients and 198 healthy controls (HC)) and brain tissue (5 BT patients and 5 HC) samples based on the V3–V4 regions of 16S rDNA. We then developed diagnostic models through logistic regression and machine learning algorithms using serum EV metagenomic data to assess the ability of various dietary supplements to reduce BT risk in vivo. Models incorporating the stepwise method and the linear discriminant analysis effect size (LEfSe) method yielded 12 and 29 significant genera as potential biomarkers, respectively. Models using the selected biomarkers yielded areas under the curves (AUCs) >0.93, and the model using machine learning resulted in an AUC of 0.99. In addition, Dialister and [Eubacterium] rectale were significantly lower in both blood and tissue samples of BT patients than in those of HCs. In vivo tests showed that BT risk was decreased through the addition of sorghum, brown rice oil, and garlic but conversely increased by the addition of bellflower and pear. In conclusion, serum EV metagenomics shows promise as a rich data source for highly accurate detection of BT risk, and several foods have potential for mitigating BT risk.Subject terms: Diagnostic markers, Machine learning     

Electrodeposition of Silver Vanadate Films: A Tale of Two Polymorphs

Two polymorphs of AgVO₃, namely the α- and β- forms, were prepared and their physical, structural, optical, electrochemical, and photoelectrochemical characteristics were compared using a battery of experimental and theoretical tools. A two-step method, previously developed in the our laboratory for the electrodeposition of inorganic semiconductor films, was applied to the electrosynthesis of silver vanadate (AgVO₃) films on transparent, conducting oxide surfaces. In the first step, silver was cathodically deposited from a non-aqueous bath containing silver nitrate. In the second step, the silver film was anodically stripped in an aqueous medium containing ammonium metavanadate. The anodically generated silver ions at the interface underwent a precipitation reaction with the vanadate species to generate the desired product in situ. Each of these steps were mechanistically corroborated via the use of electrochemical quartz crystal microgravimetry, used in conjunction with voltammetry and coulometry. As-deposited films were crystalline and showed p-type semiconductor behavior. Theoretical insights are provided for the electronic origin of the α→β phase transformation in AgVO₃ and the disparate optical band gaps of the two polymorphs. Finally, implications for the application of this material in solar cells are provided.     

sensor fault detection observer design for nonlinear systems in Takagi–Sugeno’s form

This paper addresses sensor fault detection observer design problems for discrete- and continuous-time nonlinear systems in Takagi–Sugeno’s (T–S) form. It is desired that the fault detection observer is as sensitive to fault and robust against disturbance as possible. To this end, sufficient conditions for stable T–S fuzzy model-based observer design with performance are derived in terms of linear matrix inequalities in both cases. An example on the backing-up problem of a truck-trailer is provided to illustrate the effectiveness of the proposed methodology.