Identification of Multiple Domains of Entamoeba histolytica Intermediate Subunit Lectin-1 with Hemolytic and Cytotoxic Activities

Galactose and N-acetyl-D-galactosamine-inhibitable lectin of Entamoeba histolytica have roles in the pathogenicity of intestinal amoebiasis. Igl1, the intermediate subunit lectin-1 of E. histolytica, has been shown to have both hemolytic and cytotoxic activities that reside in the C-terminus of the protein. To identify the amino acid regions responsible for these activities, recombinant proteins were prepared and used in hemolytic and cytotoxic assays. The results revealed that Igl1 has multiple domains with hemolytic and cytotoxic activities and that amino acids 787-846, 968-1028 and 1029-1088 are involved in these activities. The hemolytic activities of the fragments were partly inhibited by mannose, galactose and N-acetylgalactosamine, and glucose showed lower or negligible inhibitory effects for the activities. This is the first report of a protozoan protein with hemolytic and cytotoxic activities in multiple domains.     

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.     

Characteristics of the Arc Voltage of a High‐Current Air Arc in a Sealed Chamber

The effect of the arc voltage on various factors of design and control was investigated for high currents in order to develop design guidelines for circuit breakers. In this study, the dependence on such factors, namely, the current, arc length, electrode surface area, and internal pressure of the arc voltage, was evaluated quantitatively. As a result of the evaluations, it was estimated that the arc voltage near the electrode surface rises linearly with the arc current and the power ?0.8 of the surface area, and that the voltage in the arc column rises as the 0.3 power of the pressure increase. We confirmed the validity of the estimated voltage characteristics by comparison with the generated voltage in an actual arc‐extinction chamber. The characteristics of the estimated voltage can provide effective guidelines for the design of arc extinguishing chambers. © 2013 Wiley Periodicals, Inc. Electr Eng Jpn, 186(1): 34–42, 2014; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.22487     

Cerebral Hyperperfusion after Revascularization Inhibits Development of Cerebral Ischemic Lesions Due to Artery-to-Artery Emboli during Carotid Exposure in Endarterectomy for Patients with Preoperative Cerebral Hemodynamic Insufficiency: Revisiting the “Impaired Clearance of Emboli” Concept

The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. Diffusion-weighted magnetic resonance imaging (DWI) was performed within 24 h after surgery. Of 32 patients with a combination of reduced cerebrovascular reactivity to acetazolamide on preoperative brain perfusion SPECT and MES during carotid exposure, 14 (44%) showed cerebral hyperperfusion (defined as postoperative CBF increase ≥100% compared with preoperative values), and 16 (50%) developed DWI-characterized postoperative cerebral ischemic lesions. Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001–0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the “impaired clearance of emboli” concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA.     

Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma

Simple SummaryChondrosarcomas develop chemoresistance to standard anticancer drugs, making it difficult to control unresectable or metastatic chondrosarcomas. To improve the clinical outcomes of chondrosarcoma, new treatment approaches, such as molecule-targeting agents and immunotherapy, are needed. Recent research has revealed promising biomarkers and therapeutic targets for chondrosarcoma. In addition, several molecule-targeting agents have shown favorable antitumor activities in several clinical studies in patients with advanced sarcomas, including chondrosarcoma. This review summarizes recent basic studies on biomarkers and therapeutic targets and recent clinical studies on treating chondrosarcomas.AbstractDue to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel therapeutic approaches, such as molecule-targeting drugs and immunotherapy, are required to improve clinical outcomes in patients with advanced chondrosarcoma. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including IDH1/2 and COL2A1. Several molecule-targeting agents and immunotherapies have shown favorable antitumor activity in clinical studies in patients with advanced chondrosarcomas. This review summarizes recent basic studies on biomarkers and molecular targets and recent clinical studies on the treatment of chondrosarcomas.     

Effect of Deposition Rate on the Stress Evolution of Plasma-Sprayed Yttria-Stabilized Zirconia

The deposition rate plays an important role in determining the thickness, stress state, and physical properties of plasma-sprayed coatings. In this article, the effect of the deposition rate on the stress evolution during the deposition (named evolving stress) of yttria-stabilized zirconia coatings was systematically studied by varying the powder feed rate and the robot-scanning speed. The evolving stress during the deposition tends to increase with the increased deposition rate, and this tendency was less significant at a longer spray distance. In some cases, the powder feed rate had more significant influence on the evolving stress than the robot speed. This tendency can be associated with a deviation of a local deposition temperature at a place where sprayed particles are deposited from an average substrate temperature. At a further higher deposition rate, the evolving stress was relieved by introduction of macroscopic vertical cracks as well as horizontal branching cracks.     

Transient current mapping obtained from silicon photodiodes using focused ion microbeams with several hundreds of MeV

Single Event Effects (SEEs) triggered by energetic heavy ions traversing a sensitive parts of electric devices have been studied using high-energy heavy ion microbeams connected with Transient Ion Beam Induced Current (TIBIC) measuring system at the Japan Atomic Energy Agency (JAEA) Takasaki Ion Accelerators for Advanced Radiation Applications (TIARA) facility. In the TIBIC system, SEE for semiconductor device, that is fast charge collection, has been observed in timescales of the order of picoseconds. In this paper, we show successful demonstration of the performance of the system, in which clear images of TIBIC map have been observed for Si pin photodiodes irradiated by 260 MeV ²⁰Ne⁷⁺ and also by 520 MeV ⁴⁰Ar¹⁴⁺ microbeams.