Nicotine, a primary component of tobacco, is one of the most abused drugs worldwide. Approximately four million people die each year because of diseases associated with tobacco smoking. Mesolimbic dopaminergic neurons mediate the rewarding effects of abused drugs, including nicotine. Here we show that the tissue plasminogen activator (tPA)-plasmin system regulates nicotine-induced reward and dopamine release by activating protease activated receptor-1 (PAR1). In vivo microdialysis revealed that microinjection of either tPA or plasmin into the nucleus accumbens (NAc) significantly potentiated whereas plasminogen activator inhibitor-1 reduced the nicotineinduced dopamine release in the NAc in a dose-dependent manner. Nicotine-induced dopamine release was markedly diminished in tPA-deficient (tPA Ϫ/Ϫ )mice, and the defect of dopamine release in tPA Ϫ/Ϫ mice was restored by microinjection of either exogenous tPA or plasmin into the NAc. Nicotine increased tPA protein levels and promoted the release of tPA into the extracellular space in the NAc. Immunohistochemistry revealed that PAR1 immunoreactivity was localized to the nerve terminals positive for tyrosine hydroxylase in the NAc. Furthermore, we demonstrated that plasmin activated PAR1 and that nicotine-induced place preference and dopamine release were diminished in PAR1-deficient (PAR1 Ϫ/Ϫ ) mice. Targeting the tPA-plasmin-PAR1 system would provide new therapeutic approaches to the treatment of nicotine dependence.

In the central nervous system, tissue plasminogen activator (tPA) plays a role in synaptic plasticity and remodeling. Our recent study has suggested that tPA participates in the rewarding effects of morphine by regulating dopamine release. In this study, we investigated the role of tPA in methamphetamine (METH)-related reward and sensitization. Repeated METH treatment dose-dependently induced tPA mRNA expression in the frontal cortex, nucleus accumbens, striatum and hippocampus, whereas single METH treatment did not affect tPA mRNA expression in these brain areas. The METH-induced increase in tPA mRNA expression in the nucleus accumbens was completely inhibited by pre-treatment with R(+)-SCH23390 and raclopride, dopamine D1 and D2 receptor antagonists, respectively. In addition, repeated METH treatment increased tPA activity in the nucleus accumbens. There was no difference in METH-induced hyperlocomotion between wild-type and tPA-deficient (tPA-/-) mice. On the other hand, METH-induced conditioned place preference and behavioral sensitization after repeated METH treatment were significantly reduced in tPA-/-mice compared with wild-type mice. The defect of behavioral sensitization in tPA-/-mice was reversed by microinjections of exogenous tPA into the nucleus accumbens. Our findings suggest that tPA is involved in the rewarding effects as well as the sensitization of the locomotor-stimulating effect of METH.

The design and functionalization of reaction space around catalytic centers may promote catalysis. [1][2][3] With their unique three-dimensional globular structures, microgel-core star polymers [4][5][6][7][8] are intriguing as scaffolds that enclose catalysts: the central core is not only compartmentalized by linear-arm polymers but is also locally heterogeneous (cross-linked network), while the molecule as a whole is completely homogeneous and soluble through its soluble surrounding arms. Given these features, core-functionalized star polymers [5][6][7][8] have been developed as a new type of macromolecularly supported catalysts with a unique reaction space. For example, we have synthesized such star polymer catalysts by metal-catalyzed living radical polymerization [9,10] (Scheme 1) by in situ direct encapsulation ("tandem catalyst interchange") of ruthenium complexes into the microgel core that carries multiple phosphine ligands.[5] These "metalbearing" star polymers efficiently catalyzed hydrogen-transfer reactions with high activity, versatility, and recyclability, in comparison to their homogeneous or polymer-supported counterparts.[3]Herein, we report living radical polymerization in microgel-core reaction vessels of metal-bearing star polymers obtained by tandem catalyst interchange (Scheme 1). These star catalysts are well soluble, but the metal complexes are caged (i.e., protected) within the microgel network and lead to high activity and stability, functionality tolerance, and catalyst recycling, among others. This work is to demonstrate that the star-catalyzed system enables a novel homogeneous compartmentalized polymerization in a catalyst-embedded core, which is to be clearly distinguished from the polymerizations with conventional polymer-supported insoluble catalysts [11] and those in heterogeneous dispersed or emulsion systems particularly in terms of catalytic activity, functionality tolerance, and recyclability, among other feartures expected. [12] To successfully apply star polymer catalysts to the polymerization, PPh 3 -star S3 was synthesized by a one-pot tandem route consisting of: 1) the synthesis of RuCl 2 -Star S1 by the ruthenium-catalyzed linking reaction of linear-arm polymers with a binfunctional linker 1 and a ligand comonomer 2; [5] 2) the in situ hydrogenation [13] of the corebound chlorine and olefin units within S1 to give hydrogenated star S2, and 3) the removal of the core-bound ruthenium complexes from S2 leading to an empty-core star S3 with nonligating phosphines. Then, new metal complexes were introduced into the core of S3, giving metal-star catalysts such as RuCp*-Star S4 to be directly employed for living polymerization. Hence, the original polymerization catalyst [RuCl 2 (PPh 3 ) 3 ] is first core-bound and then interchanged with a new complex [e.g., RuCp* or FeBr 2 ], all in situ and in one pot. Note that step (2) serves to eliminate the potentially growth-active or reactive units (halogen and olefin, respectively) from the core. The products were characterized by si...

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This paper analyzes the strength and failure behavior of plain weave composites. First, the geometrical characteristics of yarn shape, laminate stacking configuration, fiber volume fraction, and yarn packing fraction are investigated using threedimensional geometrical models. Based on the geometrical characteristics, iso-strain approach is developed to predict elastic properties, stress distributions, and strengths under tensile loading. The laminate stacking configuration and fabric waviness ratio have significant influence on the composite failure behavior. Specimens of iso-phase, out-ofphase and random-phase laminate composites are prepared. The mathematical models developed are evaluated by microscopic observation and tensile tests.

The systematic search and design of phosphine ligands (PR(3)) and amine cocatalysts resulted in obtaining pentamethyl-cyclopentadienyl (Cp*) ruthenium(II) phosphine complexes [RuCp*Cl(PR(3))(2)], which are highly active and removable catalysts, for transition-metal-catalyzed living radical polymerization of methyl methacrylate (MMA). The catalysts are conveniently prepared in situ from a tetrameric precursor [RuCp*(mu(3)-Cl)](4) and a selected phosphine (PR(3)). The combination of the meta-tolyl phosphine [P(m-Tol)(3)] ligand and a primary diamine cocatalyst [NH(2)(CH(2))(6)NH(2)] provides a highly active catalytic system with precision control of the molecular weight of the polymer. The high activity enables a low catalyst dose and a high turn-over frequency without deteriorating the controllability. A hydrophilic amine cocatalyst (amino alcohol) in place of the diamine, further forms an active and removable catalyst; simple treatment with acidic water gave colorless polymers visually free from metal residues (>97 % removal; <64 ppm).

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The mineralogy of sedimentary iron ores from the Gunma iron mine are described to evaluate the role of microorganisms and plants in ore formation. The iron ore is composed of nanocrystalline goethite, well-crystallized jarosite and very small amounts of strengite. The ore characteristically occurs as thick-bands of alternating goethite and jarosite bands, thin-bands of different goethite grain sizes, and fossil-aggregate ore rich in moss and/or leaves. Algal fossils are clearly preserved in the goethite bands in the thick-banded ore. Lattice imaging showed characteristic crystallographic orientations of the goethite nanocrystals. The thin-banded iron ores consist of micrometer-sized chestnut-burr-like goethite aggregates, probably formed by bacterial iron biomineralization. The bands may be attributed to biological or seasonal rhythms. Various products of biomineralization are found in the present-day pH 2-3, Fe 2ϩ -, and SO -rich streams. Bacterial precipitation had var-2Ϫ 4 iations from amorphous Fe-P-(S) precipitates near the outlet of mineral spring to Fe-P-S precipitates and to Fe-S-(P) (schwertmannite-like) precipitates in the midstream. Mosses and green algae are also collecting Fe precipitates in and around the living and dead cells. Comparison of the processes occurring in the present-day streams and the iron-ore specimens supports the interpretation of these ores as the product of biomineralization.