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This study reports the synthesis of a flexible light‐emitting polymer film by casting the solution formed by blending poly[2‐methoxy‐5‐((2‐ethylhexyl)oxy)‐1,4‐phenylenevinylene] (MEH‐PPV) with poly(styrene‐co‐butadiene‐co‐styrene) (SBS). Scanning force microscopy (SFM) and differential scanning calorimetry (DSC) confirm that MEH‐PPV molecules are selectively positioned in the polystyrene (PS) domain of the fabricated film. As MEH‐PPV molecules are dissolved in the PS phase without aggregation, the photoluminescence (PL) spectrum of the MEH‐PPV/SBS film exhibits a nanometer‐scale bicontinuous luminescent domain with low aggregation quenching. Furthermore, the MEH‐PPV/SBS film exhibits typical elastomeric characteristics (with linear elasticity, a plateau, and densification regions in its stress–strain curves), and its tensile properties are comparable to those of neat SBS films. As MEH‐PPV molecules are almost absent in the polybutadiene (PB) phase (which influences the bulk‐film elastic properties), the concentration of MEH‐PPV shows very little effect on the elastic properties of the composite film. [ABSTRACT FROM AUTHOR]

A polyurethane foam (PUF) loaded with poly(3‐hexylthiophene) (P3HT) nanofibers is fabricated as a thermoelectric (TE) material with low‐thermal conductivity. To date, there have been no reports on PUFs loaded with organic fillers, including conducting polymers, exhibiting TE properties. The P3HT nanofibers do not affect the polyurethane foaming reaction and are uniformly dispersed in the PUF. Generally, conductive fillers, including carbon fillers, result in brittle PUFs. However, the PUFs loaded with P3HT nanofibers exhibit mechanical strength and Young's modulus comparable to the PUFs without fillers, and the thickness can be completely restored even after compressing 20 times. Finally, it is confirmed that the PUF loaded with P3HT nanofibers exhibits TE properties, and the Seebeck coefficient is approximately 3 mV K−1, which is comparable to that of the conventional P3HT film reported previously. The soft PUF loaded with P3HT nanofibers can be regarded as a TE material with flexibility, mechanical toughness, and low‐thermal conductivity. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor activator inhibitor‐1 (HAI‐1, also known as SPINT1) is an inhibitor of matriptase, a type‐2 transmembrane protease widely expressed in epithelial cells. HAI‐1 also functions as a chaperone to maintain the processing and localization of matriptase required for epithelial integrity. However, mechanisms underpinning the chaperone function remain to be elucidated. Here, we show that the first Kunitz domain (KD1) and the adjacent polycystic kidney disease (PKD) domain‐like internal domain of HAI‐1 are essential for the chaperone function. In HEK293T cells, which do not express endogenous HAI‐1 or matriptase, forced matriptase overexpression was unsuccessful unless sufficient HAI‐1 was co‐expressed. Among mutant HAI‐1 constructs, HAI‐1 with inactivation mutation in KD1 (HAI‐1mKD1) or HAI‐1 lacking the PKD domain (HAI‐1dPKD) was unable to support matriptase expression, and neither mutant formed a complex with activated matriptase. Matriptase did not localize to the cell surface when co‐expressed with HAI‐1dPKD. Moreover, HAI‐1dPKD accumulated in the cytoplasm of HEK293T and HaCaT cells rather than localizing to the cell surface, presumably due to misfolding as judged by altered antibody recognition. On the other hand, activationlocked and activity‐incompetent matriptase were stable and readily overexpressed and localized to the cell surface without HAI‐1. Therefore, the observed matriptase instability was caused by its own catalytic activity in the absence of inhibitory HAI‐1. The matriptase chaperone function of HAI‐1 is thus mediated primarily by the inhibition of undesired intracellular matriptase activity, and the PKD domain is essential for the proper folding and trafficking of inhibitory HAI‐1 and its chaperone function. [ABSTRACT FROM AUTHOR]

Summary: Background: Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required. Objective: We conducted a multicentre, open‐label, randomised, non‐inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever. Methods: Patients with haematological malignancies who developed fever refractory to broad‐spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d). Results: Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model‐based estimate of a 4% difference (90% CI, −12% to 20%), did not fulfil the statistical non‐inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3‐4 hypokalaemia‐related events than LAmB group patients (P <.01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P =.07). Conclusion: ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non‐inferiority. [ABSTRACT FROM AUTHOR]

The growth, survival, and metabolic activities of multicellular organisms at the cellular level are regulated by intracellular signaling, systemic homeostasis and the pericellular microenvironment. Pericellular proteolysis has a crucial role in processing bioactive molecules in the microenvironment and thereby has profound effects on cellular functions. Hepatocyte growth factor activator inhibitor type 1 (HAI‐1) and HAI‐2 are type I transmembrane serine protease inhibitors expressed by most epithelial cells. They regulate the pericellular activities of circulating hepatocyte growth factor activator and cellular type II transmembrane serine proteases (TTSPs), proteases required for the activation of hepatocyte growth factor (HGF)/scatter factor (SF). Activated HGF/SF transduces pleiotropic signals through its receptor tyrosine kinase, MET (coded by the proto‐oncogene MET), which are necessary for cellular migration, survival, growth and triggering stem cells for accelerated healing. HAI‐1 and HAI‐2 are also required for normal epithelial functions through regulation of TTSP‐mediated activation of other proteases and protease‐activated receptor 2, and also through suppressing excess degradation of epithelial junctional proteins. This review summarizes current knowledge regarding the mechanism of pericellular HGF/SF activation and highlights emerging roles of HAIs in epithelial development and integrity, as well as tumorigenesis and progression of transformed epithelial cells. [ABSTRACT FROM AUTHOR]

Furthermore, it is confirmed that the PUF loaded with P3HT nanofibers exhibits thermoelectric (TE) properties. This cover image designed by Takeshi Shimomura features a soft polyurethane form (PUF) loaded with poly (3-hexylthiophene) (P3HT) nanofibers with electrical conductivity. The PUFs loaded with P3HT nanofibers exhibit mechanical properties comparable to the PUFs without fillers, and the thickness can be completely restored even after compressing 20 times. [Extracted from the article]

Novel block copolymers, poly(3-hexylthiophene)- b-poly(ethylene oxide) (P3HT- b-PEO) were synthesized via Suzuki coupling reaction of P3HT and PEO homopolymers. The copolymers were characterized by NMR, gel permeation chromatography, differential scanning calorimeter, and UV-vis measurements. A series of devices based on the block copolymers with a fullerene derivative were evaluated after thermal or solvent annealing. The device using P3HT- b-PEO showed higher efficiency than using P3HT blend after thermal annealing. Phase-separated structures in the thin films of block copolymer blends were investigated by atomic force microscopy to clarify the relationship between morphologies constructed by annealing and the device performance. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011 [ABSTRACT FROM AUTHOR]

Type II transmembrane serine proteases (TTSPs) are structurally defined by the presence of a transmembrane domain located near the N-terminus and a C-terminal extracellular serine protease domain. The human TTSP family consists of 17 members. Some members of the family have pivotal functions in development and homeostasis, and are involved in tumorigenesis and viral infections. The activities of TTSPs are regulated by endogenous protease inhibitors. However, protease inhibitors of most TTSPs have not yet been identified. In this study, we investigated the inhibitory effect of hepatocyte growth factor activator inhibitor type 1 (HAI-1), a Kunitz-type serine protease inhibitor, on several members of the TTSP family. We found that the protease activity of a member, TMPRSS13, was inhibited by HAI-1. A detailed analysis revealed that a soluble form of HAI-1 with one Kunitz domain (NK1) more strongly inhibited TMPRSS13 than another soluble form of HAI-1 with two Kunitz domains (NK1LK2). In addition, an in vitro protein binding assay showed that NK1 formed complexes with TMPRSS13, but NK1LK2 did not. TMPRSS13 converted single-chain pro-hepatocyte growth factor (pro-HGF) to a two-chain form in vitro, and the pro-HGF converting activity of TMPRSS13 was inhibited by NK1. The two-chain form of HGF exhibited biological activity, assessed by phosphorylation of the HGF receptor (c-Met) and extracellular signal-regulated kinase, and scattered morphology in human hepatocellular carcinoma cell line HepG2. These results suggest that TMPRSS13 functions as an HGF-converting protease, the activity of which may be regulated by HAI-1. [ABSTRACT FROM AUTHOR]

Clearance of autoantibody-sensitized platelets through Fcγ receptors on phagocytic cells is one of the main mechanisms of thrombocytopenia in idiopathic thrombocytopenic purpura (ITP). We examined the FcγRIIA-131R/H and FcγRIIIA-158V/F polymorphisms in 104 adult chronic ITP patients, and in 59 healthy control subjects using polymerase chain reaction-based allele-specific restriction analysis. The frequency of FcγRIIA genotypes (131H/H, H/R, R/R) was not significantly different between patients and controls, and did not correlate with the responsiveness to treatment. In contrast, among FcγRIIIA genotypes, frequency of 158F/F homotype was smaller in ITP (P < 0·05). Furthermore, in FcγRIIIA-158V/V homotype, the complete remission (CR) rate with medication (treatment with corticosteroid or other immunosuppressive agents) was significantly higher (60%) than that in 158V/F (10%) or 158V/F plus 158F/F, (P < 0·01, P < 0·05). Conversely, the CR rate after splenectomy in 158F/F and 158V/F types (64·3% and 54·6%) was higher than in 158V/V (25%). Our results indicate that the polymorphism of FcγRIIIA, but not FcγRIIA, influences the response to treatment in ITP. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor from the producing cells, and normally remains in this form associated with the extracellular matrix. In response to tissue injury, the single-chain precursor is converted to a biologically active heterodimer by a serine protease. the activity of which is induced in the injured tissue. We have previously identified HGF activator, a serum serine protease that activates single-chain HGF. The sequence of HGF activator eDNA revealed that the HGF activator is homologous to blood-coagulation factor XIIa. In this study, we found that coagulation factor XIIa has an ability to activate single-chain HGE Factor XIIa exhibited a significant level of HGF-converting activity in the presence of dextran sulfate, although the specific activity of factor XIIa was slightly lower than that of the HGF activator. Since factor XIIa is activated during the initiation of contact activation induced by tissue injury, factor XIIa may function as an HGF-converting enzyme together with HGF activator in the injured tissue. C1-inhibitor, antithrombin III and α2-antiplasmin, that regulate the blood-clotting activity of factor XIIa, were also effective against the HGF-converting activity of factor XIIa. Furthermore. factor XIIa was not active in the HGF-converting activity in serum. Thus, the HGF-converting activity of factor XHa may be regulated by these serum inhibitors. [ABSTRACT FROM AUTHOR]