Sulfated Hyaluronan Binds to Heparanase and Blocks Its Enzymatic and Cellular Actions in Carcinoma Cells

We examined whether sulfated hyaluronan exerts inhibitory effects on enzymatic and biological actions of heparanase, a sole endo-beta-glucuronidase implicated in cancer malignancy and inflammation. Degradation of heparan sulfate by human and mouse heparanase was inhibited by sulfated hyaluronan. In particular, high-sulfated hyaluronan modified with approximately 2.5 sulfate groups per disaccharide unit effectively inhibited the enzymatic activity at a lower concentration than heparin. Human and mouse heparanase bound to immobilized sulfated hyaluronan. Invasion of heparanase-positive colon-26 cells and 4T1 cells under 3D culture conditions was significantly suppressed in the presence of high-sulfated hyaluronan. Heparanase-induced release of CCL2 from colon-26 cells was suppressed in the presence of sulfated hyaluronan via blocking of cell surface binding and subsequent intracellular NF-κB-dependent signaling. The inhibitory effect of sulfated hyaluronan is likely due to competitive binding to the heparanase molecule, which antagonizes the heparanase-substrate interaction. Fragment molecular orbital calculation revealed a strong binding of sulfated hyaluronan tetrasaccharide to the heparanase molecule based on electrostatic interactions, particularly characterized by interactions of (−1)- and (−2)-positioned sulfated sugar residues with basic amino acid residues composing the heparin-binding domain-1 of heparanase. These results propose a relevance for sulfated hyaluronan in the blocking of heparanase-mediated enzymatic and cellular actions.     

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.     

Room temperature c.w. operation of InGaAsP/InP heterostructure lasers emitting at 1.56 ?m

Room-temperature c.w. operation of InGaAsP/InP heterostructure lasers grown by liquid-phase epitaxy was achieved at 1.56 ?m. An active InGaAsP layer was essentially sandwiched by InP, though a thin InGaAsP buffer layer was deposited to prevent the melt-back of the active layer. Threshold current was typically 300 mA for a 17 ?m wide oxide-defined stripe laser.     

Microgenerator Using BiSbTe-Pt Thermopile and Pt-Al<Subscript>2</Subscript>O<Subscript>3</Subscript> Ceramic Combustor

The performance of a microcombustor thermoelectric generator device based on a thermopile using p-type Bi_0.3Sb_1.7Te₃ (BST) and n-type Pt films has been investigated. The BST films were prepared by two different methods—pulsed laser deposition (PLD) and sputter deposition—on Si₃N₄/SiO₂ multilayers on Si substrate. The ceramic catalyst combustor was patterned on the thermopile end on a thin membrane fabricated by back-side bulk etching of the silicon substrate. At 138°C the thermoelectric power factors of the PLD and sputter-deposited films were 3.6 × 10⁻³ W/mK² and 0.22 × 10⁻³ W/mK², respectively. The power from the generator with the sputter-deposited film was 0.343 μW, which was superior to that of the device with the PLD film, which provided 0.1 μW, for combustion of a 200 sccm flow of 3 v/v% hydrogen in air.     

Criteria for versatile GaN MOVPE tool:high growth rate GaN by atmospheric pressure growth

Growth rate has a direct impact on the productivity of nitride LED production.Atmospheric pressure growth of GaN with a growth rate as high as 10μm/h and also Al_0.1Ga_0.9N growth of 1μm/h by using 4 inch by 11 production scale MOVPE are described.XRD of（002） and（102） direction was 200 arcsec and 250 arcsec, respectively.Impact of the growth rate on productivity is discussed.     

The drying shrinkage of cellulosic fibres and isotropic paper sheets

We present theory for the shrinkage on drying of the cross-sectional area of cellulosic fibres and show that this depends on their initial moisture content only. For the linear shrinkage of cross-sectional dimensions, an additional parameter is required, which we estimate from comparison of the theory with experimental data from the literature. We proceed to combine our model of fibre shrinkage with probabilistic theory for fibre contacts in random fibrous networks to obtain a model for the unrestrained shrinkage of isotropic paper sheets. The expression obtained depends only on the moisture content of fibres and the extent of inter-fibre contact and exhibits good agreement with experimental data for laboratory-formed paper sheets. The results have relevance to the commercial manufacture of paper and potential for application to the study of cellulose nano-composites.     

Blunt corners of WC grains induced by lowering carbon content in WC–12mass%Co cemented carbides

Habit planes at WC/Co interfaces were investigated from a viewpoint of carbon content in WC–12mass%Co cemented carbides by transmission electron microscopy (TEM). WC/Co interfaces typically consist of (0001) and { 10[`1]0} { 10bar{1}0} habit planes with blunt corners, which are very close to { 10[`1]1} { 10bar{1}1} habit plane. The sizes of the blunt corners increase as the carbon content decrease. The expansions of blunt corners are due to the change in interface energy caused by the variation of the carbon content. The change in interface energy is discussed in terms of the incoherency between the (0001) planes of the WC grains and the Co-phase.     

Evaluation of three-dimensional effects in short deep beams using a rigid-body-spring-model

Three-dimensional (3-D) effects in short deep beams without stirrups that failed in shear were investigated experimentally and analytically. Two deep beams with a shear span to depth ratio (a/d) of 0.5 and with different beam widths were tested. The effect of beam width on load-carrying capacity, failure mode, crack pattern and 3-D behavior was investigated, and shape effect due to beam width was clarified. In addition, the beams were analyzed by the 3-D rigid-body-spring model (RBSM). RBSM is a discrete form of modeling that presents realistic behavior from cracking to failure, and 3-D RBSM is applicable to simulate 3-D behavior as well as the confinement effect of concrete. Analytical results in terms of load–displacement curves and crack pattern are compared with the experimental results. Three-dimensional deformations, strut widths and cross-sectional stress distribution are investigated analytically and compared with the experimental results to determine 3-D behavior in detail. The 3-D effects in short deep beams are clarified.     

Classification of particles by centrifugal separator and analysis of the fluid behavior

This study gives fundamental knowledge on the particle classification performance by centrifugal separator.It is found that the cut size of a centrifugal separator decreases as the rotational speed increases and the liquid flow rate decreases. Fitting our experimental results with the theory, they agree with each other at high flow rate. However, the difference between them generates at low flow rate. This is because dead spaces are generated in the centrifugal separator at the low flow rate. Also, the computer simulation of the fluid behavior in the centrifugal separator can find the decrease of the velocity near the wall under the low flow rate, which suggests the possibility of the formation of dead spaces in the separator.     

New technique for bonding hydroxyapatite ceramics and magnesium alloy by hydrothermal hot-pressing method

The solidification of hydroxyapatite (HA:Ca₁₀(PO₄)₆(OH)₂) and its bonding with Magnesium (Mg) alloys (AZ31; Mg–3Al–1Zn) were achieved simultaneously by using a hydrothermal hot-pressing method at a low temperature as low as 150 °C with no special surface treatment of Mg alloy. A mixture of calcium hydrogen phosphate dihydrate and calcium hydroxide was used as a starting powder material for solidifying HA. 3-point bending tests were conducted to obtain an estimate of the fracture toughness for the HA/Mg interface as well as for the HA ceramics only. The fracture toughness tests showed that the induced crack from the pre-crack tip deviated from the HA/Mg interface and propagated into the HA. The fracture toughness determined on the bonded HA/Mg specimen was close to that of the HA ceramics only (0.30 MPam^1/2).