Analysis of bone loss with aging and menopause--using digital image processing

To study bone loss relationships to aging and menopause, cross-sectional bone mass measurements by digital image processing (DIP method), and menopause information collected by questionnaire, were analyzed on 291 women who live in Tsukude village. The results are as follows. 1) The mean DIP values (sigma GS/D, MCI) by age-stratified groups decrease with age after menopause. The rate of bone loss in sigma GS/D is almost constant, but in MCI it increases with aging. 2) In 30-year old and 40-year old age groups, the frequency distribution of DIP values is symmetrical and bell-shaped. But after the fifties the distribution is asymmetrical, with the mode of distribution deviated toward low bone mass. The change of mode with aging is larger than that of mean. This fact suggests that change of mean bone mass substantially underestimates actual bone loss from aging. 3) The change of the mean DIP values stratified by years elapsed since menopause is not especially large at start of menopause but becomes almost constant after menopause. DIP values reflect the bone loss from the aging rather than from menopause, and are beneficial to the study of bone loss in elderly women.     

High-power 1320-nm wafer-bonded VCSELs with tunnel junctions

A new long-wavelength vertical-cavity surface-emitting laser structure is described that utilizes AlGaAs-GaAs mirrors bonded to AlInGaAs-InP quantum wells with an intracavity buried tunnel junction. This structure offers complete wavelength flexibility in the 1250-1650 nm fiber communication bands and reduces the high free-carrier losses and bonded junction voltage drops in previous devices. The intracavity contacts electrically bypass the bonded junctions to reduce threshold voltage. N-type current spreading layers and undoped AlGaAs mirrors minimize optical losses. This has enabled 134/spl deg/C maximum continuous-wave lasing temperature, 2-mW room-temperature continuous-wave single-mode power, and 1-mW single-mode power at 80/spl deg/C, in various devices in the 1310-1340 nm wavelength range.     

Ideal crosslinked-polymers and their characterization in free-radical monovinyl-divinyl copolymerizations

The critical conditions in which the classical Flory-Stockmayer gelation theory (F-S theory) is applicable to monovinyl-divinyl copolymerizations were pursued in detail. The resulting prepolymers or precursors of ideal crosslinked-polymers were characterized as standard polymers for the discussion of network formation in free-radical monovinyl-divinyl copolymerizations. Methyl methacrylate was copolymerized with a small amount of ethylene dimethacrylate, butylene dimethacrylate or nonapropyleneglycol dimethacrylate in the presence of lauryl mercaptan, a chain transfer agent to reduce the occurrence of a thermodynamic excluded volume effect and intramolecular crosslinking as the primary and secondary factors, respectively, for the greatly delayed gelation in the free-radical monovinyl-divinyl copolymerizations and, moreover, to keep the primary chain length constant by inhibiting a gel effect. The ratio of the actual gel point to the theoretical one reached 1.1, supporting the validity of F-S theory. The resulting prepolymers were subjected to SEC-MALLS analysis to determine the molecular weights, the molecular-weight distributions and the radii of gyration; the correlations of molecular weight vs. elution volume and radius of gyration vs. molecular weight were useful for the characterization of the precursors of ideal network-polymers.     

Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Structural analysis of cellulose triacetate polymorphs by two-dimensional solid-state C-C and H-C correlation NMR spectroscopies

For the elucidation of the crystal structures of the two crystalline allomorphs of cellulose triacetate (CTA), namely CTA I and CTA II, two-dimensional (2D) solid-state through-bond ¹³C-¹³C and ¹H-¹³C correlations NMR techniques applied to the two crystalline allomorphs of CTA. As a result, the ¹³C and ¹H chemical shifts of the glucopyranose ring of CTA I and CTA II were completely assigned by the 2D NMR spectra of these allomorphs. On the 2D ¹³C-¹³C correlation spectrum of CTA II, two sets of the ¹³C-¹³C correlations from C1 to C6 were observed. This indicated that the CP/MAS ¹³C NMR spectrum of CTA II can be characterized by its overlapping of the ¹³C subspectra of two kinds of 2,3,6-triacetyl-anhydroglucopyranose units and that there are two magnetically non-equivalent sites in the unit cell of CTA II. In the case of CTA I, the numbers of respective ¹³C and ¹H shifts of CTA I agreed with the those of the glucopyranose residue in the allomorph, strongly suggesting that the asymmetric unit of CTA I is only one glucose residue. In addition, conformational differences in the exocyclic C5-C6 bonds between CTA I and CTA II were strongly suggested by the notable differences in the ¹H and ¹³C chemical shifts at the C6 sites of these allomorphs.     

A Modeling of Singing Voice Robust to Accompaniment Sounds and Its Application to Singer Identification and Vocal-Timbre-Similarity-Based Music Information Retrieval

This paper describes a method of modeling the characteristics of a singing voice from polyphonic musical audio signals including sounds of various musical instruments. Because singing voices play an important role in musical pieces with vocals, such representation is useful for music information retrieval systems. The main problem in modeling the characteristics of a singing voice is the negative influences caused by accompaniment sounds. To solve this problem, we developed two methods, accompaniment sound reduction and reliable frame selection. The former makes it possible to calculate feature vectors that represent a spectral envelope of a singing voice after reducing accompaniment sounds. It first extracts the harmonic components of the predominant melody from sound mixtures and then resynthesizes the melody by using a sinusoidal model driven by these components. The latter method then estimates the reliability of frame of the obtained melody (i.e., the influence of accompaniment sound) by using two Gaussian mixture models (GMMs) for vocal and nonvocal frames to select the reliable vocal portions of musical pieces. Finally, each song is represented by its GMM consisting of the reliable frames. This new representation of the singing voice is demonstrated to improve the performance of an automatic singer identification system and to achieve an MIR system based on vocal timbre similarity.      

Efficient blind dereverberation and echo cancellation based on independent component analysis for actual acoustic signals

This letter presents a new algorithm for blind dereverberation and echo cancellation based on independent component analysis (ICA) for actual acoustic signals. We focus on frequency domain ICA (FD-ICA) because its computational cost and speed of learning convergence are sufficiently reasonable for practical applications such as hands-free speech recognition. In applying conventional FD-ICA as a preprocessing of automatic speech recognition in noisy environments, one of the most critical problems is how to cope with reverberations. To extract a clean signal from the reverberant observation, we model the separation process in the short-time Fourier transform domain and apply the multiple input/output inverse-filtering theorem (MINT) to the FD-ICA separation model. A naive implementation of this method is computationally expensive, because its time complexity is the second order of reverberation time. Therefore, the main issue in dereverberation is to reduce the high computational cost of ICA. In this letter, we reduce the computational complexity to the linear order of the reverberation time by using two techniques: (1) a separation model based on the independence of delayed observed signals with MINT and (2) spatial sphering for preprocessing. Experiments show that the computational cost grows in proportion to the linear order of the reverberation time and that our method improves the word correctness of automatic speech recognition by 10 to 20 points in a RT??= 670 ms reverberant environment.     

Euphorbia tirucalli β-Amyrin Synthase: Critical Roles of Steric Sizes at Val483 and Met729 and the CH–π Interaction between Val483 and Trp534 for Catalytic Action

The functions of Val483, Trp534, and Met729 in Euphorbia tirucalli β-amyrin synthase were revealed by comparing the enzyme activities of site-directed mutants against that of the wild type. The Gly and Ala variants with a smaller bulk size at position 483 predominantly afforded monocyclic camelliol C, which suggested that the orientation of the (3S)-2,3-oxidosqualene substrate was not appropriately arranged in the reaction cavity as a result of the decreased bulk size, leading to failure of its normal folding into the chair–chair–chair–boat–boat conformation. The Ile variant, with a somewhat larger bulk, afforded β-amyrin as the dominant product. Intriguingly, various variants of Trp534 exhibited significantly decreased enzymatic activities and provided no aberrantly cyclized products, although the aromatic Phe and Tyr residues were incorporated and the steric sizes of the aliphatic residues were altered. Therefore, the Trp534 residue does not stabilize the transient cation through a cation–π interaction. Furthermore, the Trp residue, with the largest steric bulk among all natural amino acids, is essential for high enzymatic activity. Robust CH–π complexation between the Val483 and Trp534 residues is proposed herein. Altering the steric bulk at the Met729 position afforded the pentacyclic skeletons. Thus, Met729 is positioned at the E-ring formation site. More detailed insights into the functions of the Val483, Trp534, and Met729 residues are provided by homology modeling.     

Wind Force Coefficients for Designing Porous Canopy Roofs

Wind force coefficients for designing porous canopy roofs have been investigated based on a series of wind tunnel experiments. Gable, troughed and mono-sloped roofs were tested. The roof models were made of 0.5 mm thick perforated duralumin plates, the porosity of which was changed from 0 to about 0.4. Overall aerodynamic forces and moments acting on the roof model were measured in a turbulent boundary layer with a six-component force balance for various wind directions. The results indicate that the wind loads on canopy roofs generally decrease with an increase in porosity of the roof. Assuming that the roof is rigid and supported by the four corner columns with no walls, the axial forces induced in the columns are regarded as the most important load effect for discussing the design wind loads. Two loading patterns causing the maximum tension and compression in the columns are considered. Based on a combination of the lift and moment coefficients, the design wind force coefficients on the windward and leeward halves of the roof are presented for the two loading patterns as a function of the roof pitch and porosity. The effect of porosity is taken into account as a reduction factor of the wind loads.     

Discovery of a Novel Scaffold as an Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid,Longamide B

Indoleamine 2,3‐dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1‐methyl‐tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.