Stereocomplex crystallization and spherulite growth behavior of poly(l-lactide)-b-poly(d-lactide) stereodiblock copolymers

The non-isothermally and isothermally crystallized stereodiblock copolymers of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) with equimolar l-lactyl and d-lactyl units and different number-average molecular weights (M_n) of 3.9 × 10³, 9.3 × 10³, and 1.1 × 10⁴ g mol⁻¹, which are abbreviated as PLLA-b-PDLA copolymers, contained only stereocomplex crystallites as crystalline species, causing higher melting temperatures of the PLLA-b-PDLA copolymers compared to those of PLLA homopolymers. In the case of non-isothermal crystallization, the cold crystallization temperatures of the PLLA-b-PDLA copolymers during heating and cooling were respectively lower and higher than those of PLLA homopolymers, indicating accelerated crystallization of PLLA-b-PDLA copolymers. In the case of isothermal crystallization, in the crystallizable temperature range, the crystallinity (X_c) values of the PLLA-b-PDLA copolymers were lower than those of the PLLA homopolymers, and were susceptible to the effect of crystallization temperature in contrast to that of homopolymers. The radial growth rate of the spherulites (G) of the PLLA-b-PDLA copolymers was the highest at the middle M_n of 9.3 × 10³ g mol⁻¹. This trend is different from that of the PLLA homopolymers where the G values increased monotonically with a decrease in M_n, but seems to be caused by the upper critical M_n values of PLLA and PDLA chains as in the case of PLLA/PDLA blends (in other papers), above which homo-crystallites are formed in addition to stereocomplex crystallites. The disturbed crystallization of PLLA-b-PDLA copolymers compared to that of the PLLA/PDLA blend is attributable to the segmental connection between the PLLA and PDLA chains, which interrupted the free movement of those chains of the PLLA-b-PDLA copolymers during crystallization. The crystallite growth mechanism of the PLLA-b-PDLA copolymers was different from that of the PLLA/PDLA blend.     

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.     

In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats

The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain–spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior.     

Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138, -210 and -335

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.     

Type IIa RPTPs and Glycans: Roles in Axon Regeneration and Synaptogenesis

Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e., chondroitin sulfate (CS) and heparan sulfate (HS), are critical for their functions. We highlight here the significance of these interactions in axon regeneration and synaptogenesis. For example, PTPσ, a member of type IIa RPTPs, on axon terminals is monomerized and activated by the extracellular CS deposited in neural injuries, dephosphorylates cortactin, disrupts autophagy flux, and consequently inhibits axon regeneration. In contrast, HS induces PTPσ oligomerization, suppresses PTPσ phosphatase activity, and promotes axon regeneration. PTPσ also serves as an organizer of excitatory synapses. PTPσ and neurexin bind one another on presynapses and further bind to postsynaptic leucine-rich repeat transmembrane protein 4 (LRRTM4). Neurexin is now known as a heparan sulfate proteoglycan (HSPG), and its HS is essential for the binding between these three molecules. Another HSPG, glypican 4, binds to presynaptic PTPσ and postsynaptic LRRTM4 in an HS-dependent manner. Type IIa RPTPs are also involved in the formation of excitatory and inhibitory synapses by heterophilic binding to a variety of postsynaptic partners. We also discuss the important issue of possible mechanisms coordinating axon extension and synapse formation.     

Prediction of cutting forces and machining error in ball end milling of curved surfaces -II experimental verification

This paper presents the results of a series of experiments performed to examine the validity of a theoretical model for evaluation of cutting forces and machining error in ball end milling of curved surfaces. The experiments are carried out at various cutting conditions, for both contouring and ramping of convex and concave surfaces. A high precision machining center is used in the cutting tests. In contouring, the machining error is measured with an electric micrometer, while in ramping it is measured on a 3-coordinate measuring machine. The results show that in contouring, the cutting force component that influences the machining error decreases with an increase in milling position angle, while in ramping, the two force components that influence the machining error are hardly affected by the milling position angle. Moreover, in contouring, high machining accuracy is achieved in “Up cross-feed, Up cut” and “Down cross-feed, Down cut” modes, while in ramping, high machining accuracy is achieved in “Left cross-feed, Downward cut” and “Right cross-feed, Upward cut” modes. The theoretical and experimental results show reasonably good agreement.     

Simulation of rubber isostatic pressing and shape optimization of rubber mold

An elastic–plastic FEM is developed to study the fundamental features of rubber isostatic pressing of powder with a view to performing a net-shape process. Experiments are also performed. It is thus shown that the properties of the rubber, in particular Poisson's ratio, give a great influence on the shape of compact and density distribution. The thickness of the rubber mold is also influential; the thicker the mold, the closer is the shape of compact to the cavity shape. An optimization scheme is also developed, so that one is able to determine the cavity shape that gives a desired shape of compact.     

Flow around a cubic body immersed in a turbulent boundary layer

This paper reports the results of an experiment concerning flow in the vicinity of a cubic body immersed in a turbulent boundary layer which is fully developed along a tunnel floor. By changing the flow direction and body height, measurements were made of the pressure and drag acting on the body, and of the flow pattern and pressure distribution on the floor. The results indicate the changes taking place in the pressure distribution over the surface of a cubic body, the pressure drag acting on it, and the flow pattern and pressure distribution over the floor surface as the angle of incidence α is varied.     

Tree colonization trends on a sediment bar after a major flood

Tree mortality and regeneration in riparian areas are greatly influenced by flooding. The elevational distribution of Salix spp. and Robinia pseudoacacia were investigated by observing densities and standing conditions before and after a major flood on a sediment bar in the middle reaches of the Arakawa River in Kumagaya, Japan. The subsequent tree recruitment was also examined. R. pseudoacacia was easily washed away with the eroded sediment, whereas Salix spp. was found to be more tolerant. Both species were able to survive even after collapsing, provided that their roots were fully or partially embedded in the sediment. Re‐shooting of collapsed trees, rather than emergence from saplings (either by seeds or vegetative fragments), was observed to be the major method of recruitment after the flood. Therefore, tree density before the flood was unchanged, unless the trees were subject to washing away. Salix spp. recruitment was mainly observed in low‐lying areas and R. pseudoacacia in elevated areas. Recruitment from saplings was species‐specific. Salix spp. at high elevations originated mainly from shoot fragments as they need high levels of moisture for seed germination and at higher elevations, sediment moisture content is very low. R. pseudoacacia, on other hand, originated mainly from roots and seeds. At a given elevation, past recruitment patterns indicated that the annual recruitment of trees increased with tree density up to a particular threshold of recruitment density. Further increases in tree density beyond that optimum value resulted in a decline in recruitment. Furthermore, threshold density was observed to increase along with elevation for R. pseudoacacia while declining with Salix spp. Copyright © 2010 John Wiley & Sons, Ltd.