Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.     

Theranostic Agent Combining Fullerene Nanocrystals and Gold Nanoparticles for Photoacoustic Imaging and Photothermal Therapy

Developing photoactivatable theranostic platforms with integrated functionalities of biocompatibility, targeting, imaging contrast, and therapy is a promising approach for cancer diagnosis and therapy. Here, we report a theranostic agent based on a hybrid nanoparticle comprising fullerene nanocrystals and gold nanoparticles (FGNPs) for photoacoustic imaging and photothermal therapy. Compared to gold nanoparticles and fullerene crystals, FGNPs exhibited stronger photoacoustic signals and photothermal heating characteristics by irradiating light with an optimal wavelength. Our studies demonstrated that FGNPs could kill cancer cells due to their photothermal heating characteristics in vitro. Moreover, FGNPs that are accumulated in tumor tissue via the enhanced permeation and retention effect can visualize tumor tissue due to their photoacoustic signal in tumor xenograft model mice. The theranostic agent with FGNPs shows promise for cancer therapy.     

Complete erasing of ghost images on computed radiography plates and role of deeply trapped electrons

Computed radiography (CR) plates made of europium-doped Ba(Sr)FBr(I) were simultaneously exposed to filtered ultraviolet light and visible light in order to erase ghost images, i.e., latent image that is unerasable with visible light (LIunVL) and reappearing one, which are particularly observed in plates irradiated with a high dose and/or cumulatively over-irradiated. CR samples showing LIunVLs were prepared by irradiating three different types of CR plates (Agfa ADC MD10, Kodak Directview Mammo EHRM2, and Fuji ST-VI) with 50 kV X-ray beams in the dose range 8.1 mGy—8.0 Gy. After the sixth round of simultaneous 6 h exposures to filtered ultraviolet light and visible light, all the LIunVLs in the three types of CR plates were erased to the same level as in an unirradiated plate and no latent images reappeared after storage at 0 °C for 14 days. With conventional exposure to visible light, LIunVLs consistently remained in all types of CR plates irradiated with higher doses of X-rays and latent images reappeared in the Agfa M10 plates after storage at 0 °C. Electrons trapped in deep centers cause LIunVLs and they can be erased by simultaneous exposures to filtered ultraviolet light and visible light. To study electrons in deep centers, the absorption spectra were examined in all types of irradiated CR plates by using polychromatic ultraviolet light from a deep-ultraviolet lamp. It was found that deep centers showed a dominant peak in the absorption spectra at around 324 nm for the Agfa M10 and Kodak EHRM2 plates, and at around 320 nm for the Fuji ST-VI plate, in each case followed by a few small peaks. The peak heights were dose-dependent for all types of CR samples, suggesting that the number of electrons trapped in deep centers increases with the irradiation dose.     

Microstructure and mechanical properties of Pt-added and Pd-added Zr-20Nb alloys and their metal release in 1 mass% lactic acid solution

The effects of Pt and Pd addition to a Zr-20Nb alloy on its microstructure and mechanical property, as well as the elution of metals from the alloys in lactic acid solution, were investigated. The microstructure was characterized with an X-ray diffractometer (XRD), an optical microscope (OM), and a transmission electron microscope (TEM). The mechanical properties were evaluated by a tensile test. The β phase is dominantly observed in the Zr-20Nb as well as in the Pt-added and Pd-added Zr-20Nb alloys. Needle-like microstructures are observed in equiaxed grains in all alloys. Pd addition to the Zr-20Nb alloy suppresses ω phase formation more than Pt addition does. The 0.2% offset yield strength and the ultimate tensile strength of the Pt-added and Pd-added Zr-20Nb alloys increase with the Pt and Pd concentrations. XRD analysis revealed that the lattice parameter of β-Zr in the Pt-added and Pd-added Zr-20Nb alloys decreases with the Pt and Pd concentrations. Pt and Pd solute in β-Zr as a substitutional element and contribute to the increase in the strength by solid solution hardening. The addition of 2Pt and 2Pd to the Zr-20Nb alloy also improves metal elution from the alloys in lactic acid solution.     

Exact solution of a plastic hollow sphere with a Mises–Schleicher matrix

In this paper we establish the exact solution for a hollow sphere with a rigid-plastic pressure-sensitive matrix and subjected to hydrostatic tension or compression. The matrix is assumed to obey to a parabolic Mises–Schleicher criterion. The closed-form expressions of the velocity field and of the stress field are provided. These exact solutions, expressed by means of the Lambert W function, allow to assess and discuss existing results.     

Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current,If, in Adult Mouse Heart Primary Pacemaker Myocytes

A number of distinct electrophysiological mechanisms that modulate the myogenic spontaneous pacemaker activity in the sinoatrial node (SAN) of the mammalian heart have been investigated extensively. There is agreement that several (3 or 4) different transmembrane ionic current changes (referred to as the voltage clock) are involved; and that the resulting net current interacts with direct and indirect effects of changes in intracellular Ca²⁺ (the calcium clock). However, significant uncertainties, and important knowledge gaps, remain concerning the functional roles in SAN spontaneous pacing of many of the individual ion channel- or exchanger-mediated transmembrane current changes. We report results from patch clamp studies and mathematical modeling of the hyperpolarization-activated current, I_f, in the generation/modulation of the diastolic depolarization, or pacemaker potential, produced by individual myocytes that were enzymatically isolated from the adult mouse sinoatrial node (SAN). Amphotericin-mediated patch microelectrode recordings at 35 °C were made under control conditions and in the presence of 5 or 10 nM isoproterenol (ISO). These sets of results were complemented and integrated with mathematical modeling of the current changes that take place in the range of membrane potentials (−70 to −50 mV), which corresponds to the ‘pacemaker depolarization’ in the adult mouse SAN. Our results reveal a very small, but functionally important, approximately steady-state or time-independent current generated by residual activation of I_f channels that are expressed in these pacemaker myocytes. Recordings of the pacemaker depolarization and action potential, combined with measurements of changes in I_f, and the well-known increases in the L-type Ca²⁺ current, I_CaL, demonstrated that I_CaL activation, is essential for myogenic pacing. Moreover, after being enhanced (approximately 3-fold) by 5 or 10 nM ISO, I_CaL contributes significantly to the positive chronotropic effect. Our mathematical model has been developed in an attempt to better understand the underlying mechanisms for the pacemaker depolarization and action potential in adult mouse SAN myocytes. After being updated with our new experimental data describing I_f, our simulations reveal a novel functional component of I_f in adult mouse SAN. Computational work carried out with this model also confirms that in the presence of ISO the residual activation of I_f and opening of I_CaL channels combine to generate a net current change during the slow diastolic depolarization phase that is essential for the observed accelerated pacemaking rate of these SAN myocytes.     

Corrosion characteristics of reduced activation ferritic steel, JLF-1 (8.92Cr–2W) in molten salts Flibe and Flinak

Static corrosion tests were performed in molten salts, LiF–BeF₂ (Flibe) and LiF–NaF–KF (Flinak), at 500 °C and 600 °C for 1000 h. The purpose is to investigate the corrosion characteristics of reduced activation ferritic steels, JLF-1 (8.92Cr–2W) in the fluids. The concentration of hydrogen fluoride (HF) in the fluids was measured by slurry pH titration method before and after the exposure. The HF concentration determined the fluoridation potential. The corrosion was mainly caused by dissolution of Fe and Cr into the fluids due to fluoridation and/or electrochemical corrosion. Carbon on the surface might be dissolved into the fluids due to the corrosion, and this resulted to the decrease of carbide on the surface. The corrosion depth of the JLF-1 specimen, which was obtained from the weight losses, was 0.637 μm in Flibe at 600 °C and 6.73 μm in Flinak at 600 °C.     

Neutronic and thermodynamic feasibility of UF6-NpF6 fueled transmutation reactor

Transmutation of neptunium, which is contained in radioactive wastes discharged from nuclear reactors, was investigated as a substitutional method for geologic disposal. We proposed a transmutation reactor fueled with a mixture of gaseous ²³³UF₆ and ²³⁷NpF₆. Neutronic and thermodynamic analysis of the reactor revealed the feasibility of the concept. The reactor has two principal advantages: (1) use of the fuel gas enables on-line reprocessing, (2) ²³⁷Np can be transmuted by a high neutron flux. Our calculation indicated that the transmutation rate of ²³⁷Np was 335 g/year/MW_th, which is much larger than the annual yield of ²³²Np in PWR (6.19 g/year/MW_th).     

Characterization of the Key Aroma Compounds of Citrus flaviculpus Hort. ex Tanaka by Aroma Extraction Dilution Analysis

ABSTRACT: The key aroma compounds were identified in Citrus flaviculpus Hort. ex Tanaka (ki-mikan) by using aroma extraction dilution analysis (AEDA) and the sniff test. Ki-mikan peel oil was extracted by cold-pressing. The highest flavor dilution (FD) factor was found for limonene. β-Phellandrene, carvacrol, spathulenol, camphene, elemol, (+)- trans -limonene oxide, and tetradecane showed higher relative flavor activity. Results of the sniff test of the original essential oil and its oxygenated fraction revealed that tetradecane, linalool, and α-terpineol were regarded as the key aroma compounds of ki-mikan peel oil. A diluted solution of linalool and α-terpineol of 3 ppm gave a ki-mikan-like flavor, while a higher concentration near 100 ppm of tetradecane tended to produce a fresh and fruity aroma note similar to ki-mikan flavor.