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.     

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.     

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.     

Lineage of non-cranial neural crest cell in the dental mesenchyme: using a lacZ reporter gene during early tooth development

The tooth is one of the ectodermal organs controlled by reciprocal interactions between the epithelium and the mesenchyme. Mesenchymal cells in the developing tooth, so-called dental mesenchymal cells, are derived from two different origins: the cranial neural crest (CNC) and the non-CNC. These CNC-derived cells migrate, proliferate and differentiate into odontoblasts, cementoblasts, fibroblasts, osteoblasts and chondroblasts. Tooth germs of wild-type mice were transplanted into the kidney of adult lacZ-transgenic mice. After 1 week of transplantation, a few lacZ-expressing cells and many red blood cells were found near or inside the blood vessels in the pulp of wild-type tooth germs. This result shows that circulating cells of the adult host could invade the dental pulp during tooth development, through the blood vessels, and be a part of dental pulp tissue. Therefore, it can be suggested that these circulating progenitor cells could be the origin of non-CNC-derived cells in tooth germ and their migration pathways would be the blood vessels invading the dental pulp during tooth development. If variations of this experiment were suitably adjusted, such as the embryonic stage of the tooth germ, duration of transplantation, etc., this transplantation experiment using adult lacZ-transgenic mice could be a good system to reveal the origin and migration pathway of cells in developing organs as well as in dental mesenchymal cells.     

Historical review of OCR research and development

Research and development of OCR systems are considered from a historical point of view. The historical development of commercial systems is included. Both template matching and structure analysis approaches to R&D are considered. It is noted that the two approaches are coming closer and tending to merge. Commercial products are divided into three generations, for each of which some representative OCR systems are chosen and described in some detail. Some comments are made on recent techniques applied to OCR, such as expert systems and neural networks, and some open problems are indicated. The authors' views and hopes regarding future trends are presented     

The growth of (InGa)As quantum wells on GaAs(111)A, (211)A and (311)A substrates

The ability to grow high quality (InGa)As on the (111)A surface is essential for the production of a wide range of optoelectronic devices, but the topic has so far received little attention. What work there has been shows it to be highly problematic, reflected in the very broad photoluminescence (PL) peaks observed for GaAs:(InGa)As multiple quantum well structures. The origin of this broadening is unclear but is certainly related to the difficulty in choosing appropriate conditions for the growth of III-Vs on the (111)A surface. We have undertaken a study of the growth of (InGa)As on the GaAs(111)A, (211)A and (311)A surfaces with the goal of achieving high quality quantum well structures, the test being the ability to obtain narrow PL line widths. We have demonstrated that 80 Å 15% InGaAs(111)A single quantum wells with 12K PL peak widths of less than 8 meV can be obtained by growth at 400°C under a V:III ratio of 5:1.     

Highly efficient four-wave mixing in an optical fiber with intensity dependent phase matching

Wavelength conversion via four-wave mixing in an optical fiber is investigated under a pump intensity dependent phase-matching condition. To obtain a high conversion gain, we use a fiber with a small mode-field diameter (4.2 /spl mu/m) and a small dispersion slope (0.0307 ps/km/nm/sup 2/). When the signal wavelength is set so that it is 9.2 nm longer than the zero-dispersion wavelength of the fiber, we obtain a wavelength conversion gain of greater than 5 dB over a pump wavelength region of more than 8 nm.     

EXOS-D (AKEBONO) very low frequency plasma wave instruments (VLF)

The Akebono (EXOS-D) satellite has been successfully observing the Earth's magnetosphere since it was launched on February 21, 1989. The objectives of VLF instruments on board the satellite were to investigate the behavior of plasma waves associated with accelerated auroral particles, wave-particle interaction mechanisms, and propagation characteristics of whistler-mode waves in the magnetosphere. The instruments measured not only the dynamic spectra of VLF waves up to 15 kHz by a wideband receiver, but also their absolute field intensities, wave normal vectors, and Poynting vectors. Two electric and three magnetic components with a bandwidth of about 50 Hz up to 12.5 kHz are sent to measure the wave normal vectors and Poynting vectors. The antenna impedance is measured to determine the correct absolute electric field intensities. The instruments have successfully measured the wave spectra, the wave normal vectors. Poynting vectors, the precise wave intensities, the antenna impedance, etc. The present paper describes the unique features of the instruments, especially the Poynting flux analyzers in more detail. Obtained scientific results are also reviewed     

Rate-distortion theory for the Shannon cipher system

Rate distortion theory is considered for the Shannon cipher system (SCS). The admissible region of cryptogram rate R, key rate R_k, legitimate receiver's distortion D, and wiretapper's uncertainty h is determined for the SCS with a noisy channel. Furthermore, inner and outer bounds of the admissible region of R, R_k, D, and wiretapper's attainable minimum distortion D˜ are derived for the SCS with a finite discrete source and a noiseless channel