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.     

Synthesis and electronic structure of proton-type partially substituted birnessite by period-four transition metal

Partially substituted proton-type birnessite were prepared by solid state reaction and their structures were refined. The formed birnessite with no substitution is identified to rhombohedral phase. In the case of substitution treatment by V and Cr for Mn, birnessite phase was not formed. On substituting Fe, hexagonal phase increased with increase of the amount of the Fe. For Co and Ni-substitution, monoclinic phase emerged at substitution ratio of around 0.37 and 0.02, respectively. For the substitution of Cu, only the monoclinic birnessite formed irrespective of the ratio. The electric conductivity of the partially substituted birnessites was examined at room temperature. The general trend is lower conductivity with increasing ratio of contained substituents. On several mol% of the substitution by Ni and Cu, the conductivity slightly increased. From DOS calculation of these compounds, the partially substitution for Mn by Fe, Co and Ni in the birnessite poses splitting of crystal field to emerge new bands at around −1 and +1 eV by Mn(IV) 3d orbital.     

Development of Sensor and Control Systems of a Wearable Robot to Walk on a Step

The goal of our study is to develop a system for walking on a step using a wearable robot. Our system consists of (1) sensing of a step from the movement of the walker, (2) detection of the foot placement state related to the step, and (3) generation of gait patterns of climbing and stepping down for the step. In the generation of gait patterns for the step, toe trajectories are generated according to the height of the step to avoid collision of the swinging leg with the step. The hip trajectory is generated by an optimization technique that minimizes the sum of the joint angular jerk of the robot subject to constraints on the hip position and the velocity at toe liftoff. Each joint angle trajectory is calculated from the generated trajectories by means of inverse kinematic equations. We investigated the feasibility of the proposed sensor and control systems for two steps with different heights.     

Homogeneous Strain Introduction Using Reciprocation Technique in High-Pressure Sliding

Metallurgical and Materials Transactions A - This study examines strain distribution occurring in the high-pressure sliding (HPS) processing for rods of pure Al and an AZ61 alloy. The strain...     

Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRAS^mt/SMAD4^mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRAS^mt/SMAD4^mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRAS^mt/SMAD4^mt cancer cells. These data indicate that the KRAS^mt/SMAD4^mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRAS^mt/SMAD4^mt signature.     

Fracture and acoustic emission characteristics of glass fiber reinforced plastics panels for hot water

This study deals with the fracture process and acoustic emission (AE) characteristics of a randomly oriented E-glass fiber mat reinforcement with a crosslinked polyester. These panels were evaluated after they were immersed in hot water. The fiber volume content of the panel was 19%. Glass fiber reinforced plastics (GFRP) panels wer immersed in water at 81°C. Bending and AE monitoring tests were Performed and after bending, the cross-section of the specimen was observed by an optical microscope and SEM. The influence of degradation, due to water immersion, on the changes of fracture process of GFRP is discussed. The dominant fracture mode of the virgin specimen was matrix cracks, whereas that of the immersed specimen was debondings at the fiber bundle/matrix and fiber/matrix interfaces. This change was caused by reduction of the bonding strength at the interface. The scale of fracture can be estimated by both AE amplitude and AE energy and this estimation method was used to estimate the fracture mode changes of GFRP panels immersed in hot water.     

Solvent- and Light-Sensitive AIEE-Active Azo Dye: From Spherical to 1D and 2D Assemblies

Fluorescent molecular assembly systems provide an exciting platform for creating stimuli-responsive nano- and microstructured materials with optical, electronic, and sensing functions. To understand the relationship between (i) the plausible molecular structures preferentially adopted depending on the solvent polarity (such as N,N-dimethylformamide [DMF], tetrahydrofuran [THF], and toluene), (ii) the resulting spectroscopic features, and (iii) self-assembled nano-, micro-, and macrostructures, we chose a sterically crowded triangular azo dye (3Bu) composed of a polar molecular core and three peripheral biphenyl wings. The chromophore changed the solution color from yellow to pink-red depending on the solvent polarity. In a yellow DMF solution, a considerable amount of the twisted azo form could be kept stable with the help of favorable intermolecular interactions with the solvent molecules. By varying the concentration of the DMF solution, the morphology of self-assembled structures was transformed from nanoparticles to micrometer-sized one-dimensional (1D) structures such as sticks and fibers. In a pink-red toluene solution, the periphery of the central ring became more planar. The resulting significant amount of the keto-hydrazone tautomer grew into micro- and millimeter-sized 1D structures. Interestingly, when THF-H₂O (1:1) mixtures were stored at a low temperature, elongated fibers were stacked sideways and eventually developed into anisotropic two-dimensional (2D) sheets. Notably, subsequent exposure of visible-light-irradiated sphere samples to solvent vapor resulted in reversible fluorescence off↔on switching accompanied by morphological restoration. These findings suggest that rational selection of organic dyes, solvents, and light is important for developing reusable fluorescent materials.     

Preparation of poly(ethylene glycol)-modified poly(amidoamine) dendrimers with a shell of hydrophobic amino acid residues and their function as a nanocontainer

We studied the use of poly(ethylene glycol) (PEG)-modified dendrimers as a nanocapsule with a biocompatible surface. We designed PEG-modified dendrimers having a shell of hydrophobic amino acid residues in the peripheral moiety of the dendrimer to increase their encapsulation ability. Subsequently, l-phenylalanine or γ-benzyl-l-glutamate residues were introduced to all chain ends of the poly(amidoamine) G4 dendrimers. Furthermore, PEG (MW 2000) chains were attached to the amino acid residues. These hydrophobic amino acid residues rendered the PEG-modified dendrimers as more compact. After binding of Rose Bengal (RB) guest molecules to dendrimers, an assay using the Klotz plot showed that the hydrophobic amino acid layer slightly affected the guest site number, but significantly increased intrinsic binding of the dendrimers to guest molecules. The PEG-modified dendrimers with the hydrophobic amino acid layer were better able to retain guest molecules than the dendrimer without the layer: they are therefore useful for drug delivery.