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.     

亚洲城市主义——公共街道中住区生活的动态性之解读

针对亚洲文脉下的高密度城市环境,提出“亚洲城市主义”作为一种新的研究和设计模式,并提出“一席之地”的概念作为环境设计中的焦点。研究关注的是“街道社会生态”,特别是在某一时刻街道上循环的事物、活动和空间结构的一幕最小的互相依赖图景,称作“社会即景”,倡导为高密度城市环境作契合文化内涵的设计。     

Locomotion Control of MEMS Microrobot Using Pulse‐Type Hardware Neural Networks

This paper presents the locomotion control of a microelectromechanical system (MEMS) microrobot. The MEMS microrobot demonstrates locomotion control by pulse‐type hardware neural networks (P‐HNN). P‐HNN generate oscillatory patterns of electrical activity like those of living organisms. The basic component of P‐HNN is a pulse‐type hardware neuron model (P‐HNM). The P‐HNM has the same basic features as biological neurons, such as the threshold, the refractory period, and spatiotemporal summation characteristics, and allows the generation of continuous action potentials. P‐HNN has been constructed with MOSFETs and can be integrated by CMOS technology. Like living organisms, P‐HNN has realized robot control without using software programs or A/D converters. The size of the microrobot fabricated by MEMS technology was 4 × 4 × 3.5 mm. The frame of the robot was made of a silicon wafer, equipped with rotary actuators, link mechanisms, and six legs. The MEMS microrobot emulated the locomotion method and the neural networks of an insect by rotary actuators, link mechanisms, and the P‐HNN. We show that the P‐HNN can control the forward and backward locomotion of the fabricated MEMS microrobot, and that it is possible to switch its direction by inputting an external trigger pulse. The locomotion speed was 19.5 mm/min and the step size was 1.3 mm. © 2013 Wiley Periodicals, Inc. Electr Eng Jpn, 186(3): 43–50, 2014; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.22473     

Connection‐Strength Estimation of Neuronal Networks by Fitting for Izhikevich Model

Recently, there has been abundant research using multineuron recording, but there are many problems with extracting the features from the obtained spike time series, which are huge in volume and complex. Here we introduce a new method of estimating synaptic connection strengths between neurons by fitting to the Izhikevich model by maximum likelihood estimation. We demonstrate that our method can estimate connection strengths from spike time series given by a simulated neural ensemble and can estimate nonconnectivity between two independent cultured neuronal networks. These results suggest that our method is applicable to network and plasticity analysis of neuronal networks.     

Solid–Liquid Phase Behaviors of Binary Mixtures of Various Partial Acylglycerols by Differential Scanning Calorimetry

Monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) are impurities in biodiesel and a major cause of precipitation. Understanding the behavior of such acylglycerols is essential for predicting biodiesel cold flow properties (CFPs). The previous study on MAG/MAG binary mixtures shows that they tend to solidify by forming molecular compounds. In contrast, TAG/TAG mixtures, which have been studied extensively, are commonly eutectic or monotectic systems, in which each component solidifies separately. The present study focuses on binary mixtures of DAG/DAG and different acylglycerol pairs (MAG/DAG, TAG/MAG, and DAG/TAG), and determination of their solid–liquid phase behavior by differential scanning calorimetry. These mixtures are found to behave as eutectic or monotectic systems with no sign of compound formation. As DAG and TAG have lower contents than MAG in biodiesel and they are unlikely to form molecular compounds with MAG, it is suggested that DAG and TAG have little effect on the biodiesel CFPs. Practical Applications: Biodiesel has attracted much interest because its blending with conventional fossil diesel has become more standard with biofuel mandates. From an energy perspective, the solid–liquid phase behavior of acylglycerols will contribute to building prediction models for biodiesel CFPs.     

Role of interfacial potential in coagulation of cuprammonium cellulose solution

The electric potential, copper ion flux, and ammonia flux across the interface of cuprammonium cellulose solution (CCS) and various 1.0 equiv/Lelectrolyte solutions (ES) at 25°C were measured. The interfacial potentials were strongly negative (–10 to –35 mV) with H₂SO_4, HCI, and (NH₄)₂SO₄ as ES, weakly positive (6 to 8 mV) with NaCl, KCl, LiCl, CsCL, and RbCl as ES, and strongly positive (19 to 34 mV) with KOH and NaOH as ES, generally showing values similar to the diffusion potentials for electrolyte solutions comprising ions of the same absolute charge. The ammonia flux (about 1 X 10^-4 mol/cm₂/s) was relatively unaffected by the interfacial potential, but the copper ion flux was clearly dependent on it. These results, together with the observed rates of CCS coagulation, indicate that the mechanism of the coagulation was largely determined by the interfacial potential, with strongly negative potential gradients accelerating the Cu²⁺ flux into the ES and CCS coagulation proceeding rapidly by Cu²⁺ removal, strongly positive potential gradients accelerating the Na⁺ flux into the CCS and coagulation proceeding rapidly via the formation of cellulose-Na⁺ complex, and the absence of a strong potential gradient capable of accelerating the ion flux resulting in slow coagulation by ammonia removal. It may therefore be possible to control the interfacial potential and the ion flux by the ES composition, and thus to influence the structure of regenerated cellulosic fibers and membranes. © 1996 John Wiley & Sons, Inc.     

Water permeation properties of SiO2-RSiO3/2 (R = methyl,vinyl, phenyl) thin films prepared by the sol-gel method on nylon-6 substrate

Nylon-6 substrates were coated with SiO₂-RSiO_3/2 (R = methyl, vinyl, phenyl) thin films by the sol-gel method, and their water permeability was evaluated Tetraethoxysilane (TEOS) and trifunctional alkoxides such as methyltriethoxysilane (MTES), vinyltriethoxysilane (VTES), and phenyltriethoxysilane (PhTES) were used as starting materials. Water permeability coefficients of the nylon-6 substrates coated with these SiO₂-RSiO_3/2 thin films were increased with an increase in the content of these trialkoxysilanes in the films. The water permeability coefficients of these coated nylon-6 substrates were smaller in the order of the systems TEOS-PhTES < TEOS-VTES < TEOS-MTES in the relatively low content of the trialkoxysilanes. © 1996 John Wiley & Sons, Inc.     

Melatonin-Induced Postconditioning Suppresses NMDA Receptor through Opening of the Mitochondrial Permeability Transition Pore via Melatonin Receptor in Mouse Neurons

Mitochondrial membrane potential regulation through the mitochondrial permeability transition pore (mPTP) is reportedly involved in the ischemic postconditioning (PostC) phenomenon. Melatonin is an endogenous hormone that regulates circadian rhythms. Its neuroprotective effects via mitochondrial melatonin receptors (MTs) have recently attracted attention. However, details of the neuroprotective mechanisms associated with PostC have not been clarified. Using hippocampal CA1 pyramidal cells from C57BL mice, we studied the involvement of MTs and the mPTP in melatonin-induced PostC mechanisms similar to those of ischemic PostC. We measured changes in spontaneous excitatory postsynaptic currents (sEPSCs), intracellular calcium concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents after ischemic challenge, using the whole-cell patch-clamp technique. Melatonin significantly suppressed increases in sEPSCs and intracellular calcium concentrations. The NMDAR currents were significantly suppressed by melatonin and the MT agonist, ramelteon. However, this suppressive effect was abolished by the mPTP inhibitor, cyclosporine A, and the MT antagonist, luzindole. Furthermore, both melatonin and ramelteon potentiated depolarization of mitochondrial membrane potentials, and luzindole suppressed depolarization of mitochondrial membrane potentials. This study suggests that melatonin-induced PostC via MTs suppressed the NMDAR that was induced by partial depolarization of mitochondrial membrane potential by opening the mPTP, reducing excessive release of glutamate and inducing neuroprotection against ischemia-reperfusion injury.     

Effects of dressing containing plant sterol on serum cholesterol concentration and the safety evaluation in borderline or mildly hypercholesterolemic Japanese subjects

In a placebo-controlled double-blind study, we examined the effects of dressing containing plant sterol (PS) on blood lipids and the safety in Japanese borderline or mildly hypercholesterolemic subjects. Fifty-nine subjects [total cholesterol (TC) concentration > or = 200 mg/dL] were randomly divided into two groups and were given daily 15 g of dressing containing 800 mg of PS [PS(+)-group] or without PS [PS(-)-group] for 12 weeks. Every 4 weeks, fasting blood was examined and subjective symptoms were analyzed. Serum TC, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) concentrations did not change in the PS(-)-group, while TC and ApoB significantly decreased in the PS(+)-group at 8 and 12 weeks and LDL-C at 4, 8 and 12 weeks. Moreover, serum TC, LDL-C and ApoB concentrations were significantly lower than those of PS(-)-group at 8 and 12 weeks. Other laboratory tests were all in normal ranges and no adverse events were observed. The results indicated that PS-containing dressing decreased serum TC, LDL-C and ApoB concentrations in borderline or mildly hypercholesterolemic subjects. It is therefore proved that the dressing containing PS is helpful in maintaining blood cholesterol level normal and hence, the health of Japanese.     

Attribute-based quality classification of academic papers

Investigating the relevant literature is very important for research activities. However, it is difficult to select the most appropriate and important academic papers from the enormous number of papers published annually. Researchers search paper databases by combining keywords, and then select papers to read using some evaluation measure—often, citation count. However, the citation count of recently published papers tends to be very small because citation count measures accumulated importance. This paper focuses on the possibility of classifying high-quality papers superficially using attributes such as publication year, publisher, and words in the abstract. To examine this idea, we construct classifiers by applying machine-learning algorithms and evaluate these classifiers using cross-validation. The results show that our approach effectively finds high-quality papers.