Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery

The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.     

Hydrated alizarin complexes: hydrogen bonding and proton transfer

We investigated the hydrogen bonding structures and proton transfer for the hydration complexes of alizarin (Az) produced in a supersonic jet using fluorescence excitation (FE), dispersed laser induced fluorescence (LIF), visible-visible hole burning (HB), and fluorescence detected infrared (FDIR) spectroscopy. The FDIR spectrum of bare Az with two O-H groups exhibits two vibrational bands at 3092 and 3579 cm(-1), which, respectively, correspond to the stretching vibration of O1-H1 that forms a strong intramolecular hydrogen bond with the C9=O9 carbonyl group and the stretching vibration of O2-H2 that is weakly hydrogen-bonded to O1-H1. For the 1:1 hydration complex Az(H(2)O)(1), we identified three conformers. In the most stable conformer, the water molecule forms hydrogen bonds with the O1-H1 and O2-H2 groups of Az as a proton donor and proton acceptor, respectively. In the other conformers, the water binds to the C10=O10 group in two nearly isoenergetic configurations. In contrast to the sharp vibronic peaks in the FE spectra of Az and Az(H(2)O)(1), only broad, structureless absorption was observed for Az(H(2)O)(n) (n≥ 2), indicating a facile decay process, possibly due to proton transfer in the electronic excited state. The FDIR spectrum with the wavelength of the probe laser fixed at the broad band exhibited a broad vibrational band near the O2-H2 stretching vibration frequency of the most stable conformer of Az(H(2)O)(1). With the help of theoretical calculations, we suggest that the broad vibrational band may represent the occurrence of proton transfer by tunnelling in the electronic ground state of Az(H(2)O)(n) (n≥ 2) upon excitation of the O2-H2 vibration.     

Standard Uncertainty Evaluation for Dynamic Tensile Properties of Auto-Body Steel-Sheets

This paper is concerned with the standard uncertainty of the true stress–true strain curve as the tensile properties of auto-body steel sheets at intermediate strain rates ranged from 1 to 100 s^?1. A procedure to obtain true stress–true strain data is properly designed for the experiment and data acquisition. An analytic model is then established to evaluate the standard uncertainty of the measurand. The measurand in this case is the true stress which is a function of the input quantities: the tensile load; the initial length, the thickness and the width of a specimen; and the deformed length of a specimen. Sources of uncertainties of the input quantities are evaluated for the high speed tensile test with their associated sensitivity coefficients. Uncertainty of the stress data acquired is also considered in the procedure of the fast Fourier transform (FFT) smoothing process used to remove unnecessary signals acquired from experiments. Image analysis using a high speed camera is carried out to measure deformation of the specimen during high speed tensile tests with proper uncertainty evaluation. A combined standard uncertainty is evaluated from the uncertainties of the input quantities as well as the influence factor for the true stress of auto-body steel sheets at intermediate strain rates. Consequently, the true stress–true strain data are obtained with proper standard uncertainty evaluation.     

Artificial control of 2D ZnO patterns using interference patterning of photodynamic polymer

A facile and economic approach was demonstrated for the artificial control of the grating period in 2D ZnO nanostructures. Highly-ordered ZnO nanostructures with various periodicities (e.g., 0.5, 1.0, 1.5, and 2.0 μm) were prepared through a combination of a controlled Ar⁺ laser interference process on a PDO3 film and spin-coating technique utilizing aqueous zinc acetate/polyvinyl alcohol (PVA) solution, which obviate the need for costly and complex processes such as a chemical etching step. The grating periods of the resulting 2D ZnO arrays are well matched with those of the photodynamically manipulated 2D surface relief grating (SRG) structure of the polymeric templates. The optical properties of 2D ZnO nanostructures with various widths and spatial densities were explored.     

EVALUATION OF DUCTILE FRACTURE CRITERIA IN A GENERAL THREE-DIMENSIONAL STRESS STATE CONSIDERING THE STRESS TRIAXIALITY AND THE LODE PARAMETER

This paper is concerned with evaluation of various ductile fracture criteria in a general three-dimensional stress state of stress triaxiality, the Lode parameter and the equiva- lent plastic strain to fracture. Evaluation is carried out by comparing fracture loci constructed by fracture criteria to experimental results of A12024-T351. Comparison demonstrates that the Modified Mohr-Coulomb criterion and a newly proposed criterion provide sufficient predictabil- ity of fracture strain. Moreover, evaluation is emphasized on the predicted cut-off value for stress triaxiality. The evaluation demonstrates that the Cockcroft-Latham, Brozzo, Oh, Ko-Huh and the new criteria coupled a reasonable cut-off value for ductile materials.     

Spontaneous formation of silver nanoparticles in aminosilica

We report a rapid and spontaneous metallization process associated with sol–gel reaction of aminosilane that can be utilized to synthesise silver embedded silica nanocomposite without involving additional reducing agents. The reduction reaction induced by bis[3-(trimethoxysilyl)propyl]ethylenediamine (enTMOS) involves amine functional moieties, which drive the reduction reaction with presence of water. Cyclic voltammetry was used to investigate the redox potential of enTMOS and its relation to chemical environment. It was found that the oxidation potential of enTMOS depending on the amount of water (water:enTMOS (v/v) = 8:1–0:1) ranges from 0.48 to 0.68 V versus Ag/AgCl electrode in methanol. The oxidation potential of aminosilane decreases with water content and becomes more negative than that of Ag, suggesting the aminosilane acts as a silver reducing agent while serving as a matrix to encapsulate silver nanoparticles after reacting with water. This process has been utilized to produce evenly dispersed silver nanoparticles with sizes ranging from 5 to 20 nm in both liquid and solid forms of aminosilane, allowing us to prepare silver nanoparticles doped silica nanocomposite that exhibits enhanced electrochemical properties.     

Reduction‐responsive poly (ethylene glycol)‐dexamethasone biarm conjugate and its self‐assembled nanomicelles: Preparation,physicochemical characterization,and thiol‐triggered drug release

In this study, a reduction‐responsive poly (ethylene glycol)‐dexamethasone biarm conjugate was synthesized as intracellular targeted drug delivery carriers. The hydroxyl end group of methoxy poly (ethylene glycol) (mPEG) was modified to introduce a biarm structure with bioreducible disulfide bond and amine end groups. Dexamethasone (Dex) as a nuclear targeting moiety was conjugated to the amine end groups of mPEG biarm derivatives, mPEG‐(NH₂)₂ or mPEG‐(ss‐NH₂)₂, with or without bioreducible disulfide bonds. The bioreducible and nonreducible mPEG‐Dex biarm conjugates, R‐mPEG‐Dex and N‐mPEG‐Dex, were synthesized and characterized by various analytical methods, proton nuclear magnetic resonance (¹H‐NMR), Fourier transform infraredspectroscopy (FT‐IR), dynamic light scattering (DLS), and fluorescence measurements. Amphiphilic mPEG‐Dex conjugates self‐assembled in aqueous solutions to form nanoparticles (NPs) with a size range of 130 to 150 nm, and their critical micelle concentrations (CMCs) were determined to be 12.4 and 15.3 mg/L, respectively, for bioreducible and nonreducible ones. The R‐mPEG‐Dex NPs maintained good colloidal stability in the presence of bovine serum albumin (BSA) for more than 1 week but demonstrated a significant change in colloidal stability in the presence of dithiothreitol (DTT). In DTT‐containing phosphate‐buffered saline (PBS), the bioreducible NPs showed not only reduction‐responsive destabilization with PEG shedding but also thiol‐dependent drug release profile. Our observations indicated that the R‐mPEG‐Dex NPs have a promising prospective as an efficient nanocarrier for intracellular targeted delivery of various anticancer drugs.     

Directional behavior of nuclear quadrupole resonance in YBa2Cu3O6

Powder samples of YBa₂Cu₃O₆ were magnetically aligned and the anisotropies in the systems were studied by means of Cu(1) nuclear quadrupole resonance (NQR) in the absence of external magnetic fields. Our room temperature measurements of the NQR lineshapes and the spin–lattice and spin–spin relaxation times as a function of the aligning magnetic field indicate that full microscopic alignment can be achieved by using a magnetic field of about 4.7 T, for which doublet line patterns arising from a hyperfine splitting were observed.