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Thermoplastic resins, which are lighter than metals and ceramics, have many features such as excellent processability. They are used in widely various fields for daily necessities and for transportation equipment. Even for the same material, the elastic properties of the thermoplastic resin can vary depending on the molecular weight, molding temperature and conditions. Therefore, the elastic properties required for structural analysis must be evaluated each time. After this study derived a formula for yield initiation stress of injection-molded thermoplastics, the formula was applied for a method of obtaining the longitudinal elastic modulus and Poisson's ratio from results of a three-point bending test. From actual examination using polypropylene (PP) and polystyrene (PS), the calculated longitudinal elastic modulus and Poisson's ratio showed good agreement with literature values. Results clarified that these values depend on the injection molding temperature. Furthermore, the bulk modulus and shear modulus were obtained from the longitudinal modulus and Poisson's ratio. Their injection molding temperature dependences were investigated. The shear modulus showed the same tendency as that of the longitudinal elastic modulus, but results indicated the dependence of bulk modulus as small in PP: bulk modulus of PS increased with increasing injection molding temperature.

Prolyl hydroxylase domain-containing protein (PHD) inhibitors are useful as orally administered agents for the treatment of renal anemia. Based on the common structures of known PHD inhibitors, we found novel PHD inhibitor 1 with a 2-[(4-hydroxy-6-oxo-2,3-dihydro-1H-pyridine-5-carbonyl)amino]acetic acid motif. The PHD2-inhibitory activity, lipophilicity (CLogP), and PK profiles (hepatocyte metabolism, protein binding, and/or elimination half-life) of this inhibitor were used as the evaluation index to optimize the structure and eventually discovered clinical candidate 42 as the suitable compound. Compound 42 was demonstrated to promote the production of erythropoietin (EPO) following oral administration in mice and rats. The predicted half-life of this compound in humans was 1.3–5.6 h, therefore, this drug may be expected to administer once daily with few adverse effects caused by excessive EPO production.

The effect of a multi-functional epoxy-based chain extender on the tensile properties of poly( l -lactic acid) (PLLA)/poly(butylene succinate-co- l -lactate) (PBSL) blends was investigated using X-ray diffraction, differential scanning calorimetry, attenuated total reflection infrared spectroscopy, solid-state nuclear magnetic resonance spectroscopy, and scanning electron microscopy. The PLLA/PBSL blend without the chain extender showed low strain at break because of its immiscible sea-island morphology. The chain extender reacted with both PLLA and PBSL during the blending process to produce three types of graft polymers. The graft polymer formed by the reaction of the chain extender with both PLLA and PBSL at the PLLA/PBSL interface improved the miscibility and tensile properties of the blend through interfacial interactions. The graft polymers connected with either PLLA or PBSL existed within the PLLA or PBSL domains, respectively and suppressed the molecular motions due to the intra-domain interactions. When 4 % chain extender was used, the miscibility of the blend improved and the suppressed molecular motions of the PBSL portion increased the maximum stress and strain at break. At the chain extender concentration of 6 %, the miscibility of the blends did not increase; however, the interfacial and intra-domain interactions increased, which deteriorated the tensile properties of the blends.

Styrenic copolymers comprising styrene, methyl methacrylate, and maleic anhydride were developed to improve the heat-resistance property of poly(methyl methacrylate) (PMMA). The optical, thermal, and mechanical properties were examined for the blend specimens prepared by an injection-molding machine using melt-mixed samples. It was found that the copolymers, which were miscible with PMMA, increase the glass transition temperature and therefore the Vicat Softening temperature. Furthermore, the blends were completely transparent as similar to PMMA.

The joining of metal and polymer surfaces is a promising technology to reduce the total weight of parts and to improve interface reliability. In this study, a micro square grid (200 μm × 200 μm) was fabricated on an aluminum surface using laser ablation. Molten glass-reinforced poly(butylene terephthalate), poly(styrene) and acrylonitrile---butadiene---styrene were introduced to the micro square grids by a precise injection molding machine. The maximum load tensile test was used as a measure of the joining strength between aluminum and the polymer. The tensile strength tests assisted in the differentiation of three modes of separation: interface-peeling, cohesive failure and matrix fracture. The maximum load increased with the effective joined area where interface-peeling was observed. The maximum load ceased at a certain effective joined area, and matrix fracture occurred. Cohesive failure was observed where the effective joined area was smaller than the area for which matrix fracture was observed, and the joined strength was larger than that observed for interface-peeling. The maximum stress, which was calculated by dividing cross-sectional area by the maximum load, at the matrix fracture was proportional to the polymer tensile strength.

This study investigated important mechanical properties, the flexural strength and flexural modulus, of polyglycolic acid (PGA) fiber-reinforced polylactic acid (PLA) composites fabricated by melt-mixing. The flexural strength and flexural modulus were estimated using three-point bending tests conducted at 37°C. Both the flexural strength and flexural modulus were increased by PGA fiber reinforcement. Viscoelastic properties were also investigated using dynamic mechanical analysis (DMA) under tensile loading. Results show that PGA fiber, which acts as the nucleate agent of PLA, restrains the molecular chains of PLA. That restraint reduces deformation at the same stress condition, thereby improving the PLA flexural properties.

Polycarbonate/acrylonitrile–butadiene–styrene (PC/ABS) blends have been used widely for specific applications such as in automotive interior and exterior parts, and for office automation equipment parts. This study was conducted to investigate the effects of a reactive polymer as a modifier on properties such as the impact strength of PC/ABS blends. A reaction between PC and maleic anhydride group cannot usually be expected because the end hydroxyl group of PC is capped with an end-capping agent such as t-butylphenol to improve PC properties such as fluidity, thermal resistance, and impact strength. However, a reactive polymer that has a maleic anhydride group reacts with the end hydroxyl group of PC hydrolyzed with metal salts. Results show that PC/ABS with a reactive polymer exhibits improved impact strength. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44550.

Fiber reinforced thermoplastics (FRTPs) are used for lightweight automobile and home appliances because of their higher specific strength and modulus compared to other materials. Although injection molding is often used in FRTPs considering productivity, an important difficulty is that the strength is reduced considerably by the weld joining the resin. This study investigated the fiber content dependence on the weld strength of injection molded fiber-reinforced polypropylene (FRP). Results suggest a negative correlation between the fiber content and weld strength. Experimentally obtained results also clarified that the FRP weld strength can be determined by the residual strain derived from thermal deformation during molding processing and the interaction force between the fiber and the matrix.

In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50=19 nM) in addition to the excellent functional antagonist activity (IC50=13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50=23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 >1 μM) or the enzymes COX-1 and COX-2 (IC50 >10 μM).

Effects of particle size distribution on physical properties such as viscosity, heat and mechanical properties of injection-molded hydroxyapatite (HA)/poly lactic acid (PLA) were investigated. The melting temperature of PLA was shifted to a lower temperature because of the dispersion of HA particles. However, the cold crystallization temperature shifted to a lower temperature at high HA composition, suggesting that HA particles acted as a nuclear agent. x c,PLA of the composites with bimodal particle size distribution showed the lowest of all three composites, suggesting that mobility of PLA polymer chain was reduced by bimodal particle size distribution, which means the increase of restriction at interface between polymer matrix and particle. Melt flow rate (MFR) increased because of dispersed HA particle. The reason was thought that hydrolysis degradation of PLA occurred during melt-mixing process is accelerated by HAp particle dispersion. The MFR of composites increased concomitantly with increased par...

A series of 5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and for their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. As a representative compound, 16i was a potent and selective ALK5 inhibitor, exhibiting a good enzyme inhibitory activity (IC50 = 5.5 nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC50 = 36 nM). Furthermore, the topical application of 3% 16i lotion significantly inhibited Smad2 phosphorylation in Mouse skin (90% inhibition compared with vehicle-treated animals).

The effects of the additive amount of a chain extender, with a weight ratio of 3–5 %, on stress-strain curves of poly(lactic acid) (PCL) and poly(butylene succinate-co-l-lactate) (PBSL) polymer blends were examined with a mixing ratio of PLA to PBSL of 70/30. The additive increased the elongation at break, and the strain rate decreased elongation at break.

Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking via type-1 S1P receptor (S1P(1)) and participates in many pathological conditions. We developed a novel type S1P(1)-selective antagonist, TASP0251078, which is structurally unrelated to S1P. This competitive antagonist inhibited binding of S1P to S1P(1) resulting in reduced signaling downstream of S1P(1), including GTPγS-binding and cAMP formation. TASP0251078 also inhibited S1P-induced cellular responses such as chemotaxis and receptor-internalization. Furthermore, when administered in vivo, TASP0251078 induced lymphopenia in blood, which is different from previously reported effects of other S1P(1)-antagonists. In a mouse contact hypersensitivity model, TASP0251078 effectively suppressed ear swelling, leukocyte infiltration, and hyperplasia. These findings provide the chemical evidence that S1P(1) antagonism is responsible for lymphocyte sequestration from the blood, and suggest that the effect of S1P(1) agonists on lymphocyte sequestration results from their functional antagonism.

Sphingosine 1-phosphate receptor type 1 (S1P(1)) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P(1) and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P(1)-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P(1) antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P(1) is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

Micro-molding of microneedle features was conducted using several injection-molding techniques. Injection compression molding and injection molding were performed with supercritical carbon dioxide fluid and with or without vacuum processing inside the mold cavity. Effects of process parameters on processability and surface replication of the molded parts were evaluated. The height replication ratio for microneedles was improved using injection compression molding. At a shorter compression stroke, the needle height was improved, and the influence of compression delay time was also small. Moreover, the effects of vacuum processing inside the mold cavity under the filling process were slight. The height replication ratio for microneedles showed the highest values using injection molding using supercritical carbon dioxide fluid with vacuum inside the mold cavity.

Injection compression molding (ICM) with high aspect ratio surface features was performed to clarify the effect of molding conditions on replication characteristics and molecular orientation distribution. Short-shot defects and surface replication were better when using ICM than when using conventional injection molding. A long compression stroke and short delay time condition were optimum conditions to used to achieve uniform surface replication. Molecular orientation was also reduced by the long compression stroke. To reduce molecular orientation, the compression motion should be carried out immediately after injection motion in the case of 0.2 mm thickness. For 0.6 mm thickness, the compression motion was conducted after the shear stress relaxation to reduce the molecular orientation. Short-shot tests revealed distinctive replication behavior in ICM. Results show that replication behavior and local molecular orientation are generated by a slightly frozen layer at the filling area before compression.

Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1 sphingosine 1-phosphate receptor (S1P1) and participates in many pathological conditions, including autoimmune diseases. We developed a novel S1P1-selective antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist competitively inhibited S1P-induced cellular responses, such as chemotaxis and receptor internalization. Furthermore, differing from previously reported S1P1 antagonists, TASP0277308 demonstrated in vivo activities to induce lymphopenia, a block in T cell egress from the thymus, displacement of marginal zone B cells, and upregulation of CD69 expression on both T and B cells, all of which recapitulate phenotypes of S1P1-deficient lymphocytes. In a mouse collagen-induced arthritis model, TASP0277308 significantly suppressed the development of arthritis, even after the onset of disease. These findings provide the first chemical evidence to our knowledge that S1P1 antagonism is responsible for immunosuppression in the treatment of autoimmune diseases and also resolve the discrepancies between genetic and chemical studies on the functions of S1P1 in lymphocytes.

Effects of LTI addition on the mode I fracture energy of HA/PLLA/PCL were examined and the micro-structural modification due to LTI addition was investigated. Both the mode I energy release rate, Gin, and averaged fracture energy, Ef, are improved dramatically due to LTI addition. The reason is considered to be the improvements of the interfacial structure connecting HA particles with PLLA/PCL matrix and the miscibility between PLLA and PCL. These changes of blend morphology and interfacial structure reduce the stress concentration and lead to the ductile deformation and resulted in the increase of those fracture properties.

We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s10nM) for Lck kinase inhibition.

We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s