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.     

Measurement of cosmic-ray neutron dose onboard a polar route flight from New York to Seoul

Exposure to cosmic radiation in operation of a jet aircraft is considered to be a part of the occupational exposure. Cosmic radiation doses received in aviation are generally evaluated by numerical model simulations. The precision of the model calculation should be verified by measurements. From the viewpoint of radiological protection, neutrons are the most contributing radiation component and have to be precisely measured. Neutron measurements were thus performed in a long-haul flight using a relatively new transportable neutron monitor (WENDI-II) which responds fairly well to the cosmic-ray neutrons. The in-flight measurement was carried out on 5-6 November 2009 on a polar route flight from New York/John F. Kennedy airport to Seoul/Incheon airport. The flying time was ~14 h. The observations obtained as 1 cm ambient dose equivalent were compared with model calculations using a computer program developed by the authors for the calculation of aviation route doses 'JISCARD EX'. Good agreements between the measured and calculated values were observed over the polar route where the geomagnetic cut-off rigidity is the lowest.     

Radiation tolerance of type IIa synthetic diamond detector for 14 MeV neutrons

Radiation tolerance of a type IIa synthetic diamond detector was examined from irradiation of mono-energetic 14 MeV neutrons. Measurements of I–V (current–voltage) characteristics and energy spectrum for 5.486 MeV alpha particles were performed after neutron irradiation. In the I–V characteristics measurement, enhancement of rectification was observed after neutron irradiation of up to 2.0 × 10¹² n/cm². Concurrently with the enhancement of rectification, significant decrease in signal amplitude was observed in energy spectrum measurement for alpha particles. It is considered that these changes were due to increase in the concentration of defects acting as shallow energy levels in the forbidden band. For neutron irradiation of higher than 1.6 × 10¹³ n/cm², weakening of the rectification characteristics and recovery of the signal amplitude were observed. These changes imply that deep energy levels, which were also considered to be introduced by defects, were dominant and weakened the effects of the shallow energy levels. Increase in the concentration of the deep trapping levels resulted in gradual decrease of the signal amplitude and degradation in the energy resolution. The peak for the alpha particles was obtained up to 5.5 × 10¹³ n/cm².     

Elevated serum lipoprotein (a) levels associated with ulcerative colitis in a young Japanese patient

Thromboembolism has been shown to play a role in the pathogenesis of inflammatory bowel disease (IBD). A possibility exists that lipoprotein (a) [Lp(a)], a newly-discovered prothrombotic factor, also participates in the development of at least some cases of IBD. Marked elevation of serum Lp(a) levels was observed in a young patient with ulcerative colitis. A biopsy specimen of the rectal mucosa showed findings compatible with ulcerative colitis, as well as small vessel thrombus occurring within the muscularis mucosa in the rectum. Serum Lp(a) levels were markedly elevated on admission (71 mg/dl), with a gradual decrease to 46 mg/dl on discharge. Moreover, serum Lp(a) levels decreased in parallel with clinical improvement. In the quiescent clinical stage, no small vessel thrombus was observed in the mucosa on follow-up colonoscopy. The association between IBD and hyper-Lp(a)-emia would be presumable but it has been, to our knowledge, previously unreported. The case reported here would be the first young patient, suggesting the presence of hyper-Lp(a)-emia and small vessel thrombus formation occurring in association with the development of ulcerative colitis.     

A Restart Control Method for Position Sensorless PMSM Drive Systems Without Potential Transformer for Railway Vehicle Traction

This paper proposes a restart control method for position sensorless PMSM drive systems without a potential transformer for railway vehicle traction. This method can estimate the initial rotor speed and position under coasting conditions over the entire speed range. The method can also be used when the back‐EMF voltage is higher than the inverter DC link voltage. The proposed method is verified by experiments using a 200‐kW PMSM.     

The metabolic pathway of visual pigment chromophore formation in Drosophila melanogaster--all-trans (3S)-3-hydroxyretinal is formed from all-trans retinal via (3R)-3-hydroxyretinal in the dark

Carotenoid-depleted fruit flies, Drosophila melanogaster, were reared on yeast/glucose medium containing lipid-depleted white corn grits and cholesterol. After rearing for more than a year, the yield of flies remained constant and the content of 3-hydroxyretinal in a head was three logarithmic units less than that of normal flies reared on medium containing yellow corn grits. When all-trans retinal was supplied as the sole source of retinoids, the flies formed and accumulated all-trans 3-hydroxyretinal in the dark. To examine the metabolic pathway to produce (3S)-3-hydroxyretinal in Drosophila, all-trans retinal was supplemented for two hours to carotenoid-depleted flies in the dark, and the subsequent changes in the composition of 3-hydroxyretinal enantiomers were analyzed using a chiral column on HPLC. The results indicated initial formation of (3R)-3-hydroxyretinal followed by isomerization into the 3S enantiomer. In another set of experiments, the membrane fraction was obtained from the head homogenate of retinoid-depleted flies and an in vitro assay of 3-hydroxyretinal formation from retinal was performed. The 3-hydroxyretinal produced was the 3R enantiomer, supporting the result obtained from the in vivo experiment whereby (3S)-3-hydroxyretinal is produced from retinal via (3R)-3-hydroxyretinal. Addition of NADPH enhanced 3-hydroxyretinal formation and the presence of carbon monoxide inhibited it, suggesting that hydroxylation at the C3 position of retinal occurred via the monooxygenase activity of cytochrome P-450.     

Grain refining of Al-4.5Cu alloy by adding an Al-30TiC master alloy

A particulate Al-30 wt pct TiC composite was employed as a grain refiner for the Al-4.5 wt pct Cu alloy. The composite contains submicron TiC particles. The addition of the TiC grain refiner to the metal alloy in the amount of 0.1 Ti wt pct effected a remarkable reduction in the average grain size in Al-4.5 wt pct Cu alloy castings. With the content of over 0.2 Ti wt pct, the grain refiner maintained its refining effectiveness even after a 3600-second holding time at 973 K. The TiC particles in the resulting castings were free of interfacial phases. It is concluded that the TiC are the nucleating agents and that they are resistant to the “fading effect” encountered with most grain refiners.     

Supermode selection of a subterahertz-harmonic colliding-pulse mode-locked semiconductor laser using continuous-wave light injection

The supermode of a 192-GHz sixth-harmonic colliding-pulse mode-locked semiconductor laser can be selected by continuous-wave (CW) light injection adjusted to the unlocked fundamental cavity modes. This selection scheme offers a technique for wide-range simultaneous multiwavelength allocation at each fundamental mode spacing and will be useful for providing standard light sources for wavelength-division multiplexed (WDM) systems.     

Surface activity of the lipid products hydrolyzed with lipase and phospholipase A-2

We examined thein vitro surface activity, immersional wettability and adhesional wettability shown by aqueous solutions of soy lysophospholipid (SLP)/monoglyceride (MG)/fatty acid (FA), SLP/FA and SLP/MG, and found that many lipid mixtures showed significant surface activity when their MG and FA components consisted of polyunsaturated FA and/or medium chain FA. The more unsaturated the FA, the higher the surface activity. A mixture of SLP/medium chain fatty acid MG (medium chain MG)/medium chain FA showed the highest surface activity, and was comparable to an Aerosol-OT surfactant, the most effective wetting agent. SLP/polyunsaturated FA monoglyceride (polyunsaturated MG)/polyunsaturated FA, SLP/medium chain FA, and SLP/polyunsaturated FA, SLP/medium chain MG, and SLP/polyunsaturated MG also showed a high degree of activity. Wettability decreased rapidly when the amount of saturated, long chain FA moieties increased. It is recognized that the degrees of unsaturation and the chain length of FAs in the lipid mixtures have a decisive influence on surface activities. Higher ratios of MG and FA to SLP gave higher activity; and solubilizers such as bile salts were necessary to dissolve them in water.