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Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 μM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3β signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.

Although pretensioned concrete structures have increasingly been used worldwide, a number of design issues need to be addressed to further improve the structural performance. Transfer length of pretensioned members was investigated with several test variables in this study by adopting various sensing technologies including the Smart Strands with embedded fiber optic sensors. The effect of increased strength in 2360 MPa high-strength strand on the transfer length was also analyzed. Representative provisions widely used in design were compared with the test results for consistency and appropriate conservatism. The strain distribution required for the transfer length depended partly on the type and location of sensors, which suggests the challenges associated with reasonable determination of the transfer length. According to the results of the analysis, the predictive equation in ACI 318 was relatively accurate and conservative under various conditions including high-strength strands. However, the transfer lengths based on the strand strains rather than the conventional surface strains of concrete require further investigation depending on the bonding behavior between the strand and the surrounding concrete inside a member. Thus, this study also introduces a new sensing technology utilizing the Smart Strand to reliably measure the strain distribution along a strand.

The developed Holed, Incrementally Prestressed Concrete (H-IPC) girder represents various advanced design concepts. First, the entire self-weight can be considerably reduced by introducing holes in the web, with minimal effect on the moment of inertia. Also, prestress can be efficiently introduced in an incremental way by distributing the anchorages at the holes. The girder can maintain the same sections throughout the span by preventing concentration of the anchorages. This can further reduce self-weight, fabricating time, and cost. Furthermore, the spliced girder system makes it possible to extend the span to more than the conventional length since the segments can be transported and prefabricated on site. The objective of this study is to verify the various advantages of the original design concepts by examining the structural behavior obtained from the loading tests of the 50 m-long full-scale girder specimens. The effect of the holes in the web on overall behavior is one of the main concerns in the test. The test results of a segmented specimen are also compared with those of a non-segmented specimen to investigate the effect of segmentation. It is demonstrated that the segmental H-IPC girder can be effectively used for the design and construction of long-span girder bridges.

The molecular mechanisms underlying susceptibility to psychostimulant addiction remain unclear. Searching for commonalities in the effects of addictive drugs on brain gene expression is a prolific approach to determine transcriptional signatures influencing drug abuse.We explored the common transcriptional responses to the reinforcing effects of psychostimulants methamphetamine, amphetamine, and methylphenidate. We also aimed to identify transcriptional changes that may subserve abuse of these drugs.Genome-wide transcriptome profiling analyses were performed to identify common prefrontal cortical (PFC) and striatal gene expression profiles in drug-naïve (cohort 1) and stimulant-pretreated (cohort 2) rats, which showed a conditioned place preference to and self-administration of methamphetamine, amphetamine, and methylphenidate.In behavioral studies, stimulant-pretreated rats showed behavioral sensitization characterized by enhanced behavioral response to the rewarding or reinforcing effects of psychostimulants. Inflammation-associated genes (e.g., Alas1, S100a8 and S100a9) were identified as the primary differentially expressed genes (DEGs) in both the PFC and the striatum of cohort 1 rats, while neuronal plasticity (Sgk1)- and brain development (e.g., Bhlhe22, Neurod1, Nr4a2, and Msx1)-associated genes comprised the major upregulated DEGs in the striatum of cohort 2 rats. Furthermore, a meta-analysis of the common striatal DEGs in this study along with morphine-regulated striatal transcriptomes in mice (National Center for Biotechnology Information-Gene Expression Omnibus Database Accession Code GSE7762) suggested similar expression profiles of genes involved in neuronal development (e.g., Bhlhe22, Nr4a2).This study provides evidence that brain development-associated genes mediate the reinforcing effects of methamphetamine, amphetamine, and methylphenidate and that these transcripts may underlie susceptibility to psychostimulant addiction.

We investigated the effect of the cAMP system on lipopolysaccharide (LPS)-induced changes in the activity of matrix metalloproteinases (MMPs) and tissue plasminogen activator (tPA) in rat primary astrocytes. LPS stimulation increased MMP-9 and decreased tPA activity in rat primary astrocytes. Co-treatment with a cAMP analog, dibutyryl-cAMP (db-cAMP), or the cAMP elevating beta-adrenergic agonist, isoproterenol, concentration-dependently inhibited LPS-induced MMP-9 activity. In contrast, db-cAMP concentration-dependently increased tPA activity in both basal and LPS-stimulated rat primary astrocytes. To confirm the effect of cAMP on MMP-9 and tPA activity, we treated LPS-stimulated astrocytes with cAMP phosphodiesterase inhibitors, IBMX or rolipram, and they exhibited similar effects to db-cAMP, namely decreasing MMP-9 activity and increasing tPA activity. RT-PCR analysis of MMP-9 mRNA expression and MMP-9 promoter luciferase reporter assays revealed transcriptional upregulation by LPS stimulation and downregulation by db-cAMP. In contrast, the level of tPA mRNA expression was increased both by LPS and by cAMP treatment. Consistent with RT-PCR analysis, tPA promoter reporter assays showed increased activity by both LPS and cAMP stimulation. Interestingly, the level of mRNA encoding plasminogen activator inhibitor-1 (PAI-1) was increased by LPS stimulation and decreased back to control level after co-treatment with db-cAMP, suggesting that PAI-1 expression plays a major role in the regulation of tPA activity. To examine PKA involvement in the effects of db-cAMP on MMP-9 and tPA activity, we added the PKA inhibitors, H89 or rp-cAMP, along with db-cAMP, and they inhibited db-cAMP-mediated changes in tPA activity without affecting MMP-9 activity. These data suggest that cAMP differentially modulates MMP-9 and tPA activity through a mechanism related to PKA activation. The differential regulation of MMP-9 and tPA by the cAMP system may confer more sophisticated regulation of physiological processes, such as extracellular matrix remodeling and cell migration, by activated astrocytes.

An advanced numerical formulation for the geometrically nonlinear finite element analysis of the shell structures under nonconservative loads is proposed in the present paper. The nonconservative follower loads are efficiently implemented by the load correction stiffness matrix(LCSM). The implications and assumptions adopted to derive LCSM are thoroughly explored in this study to take reasonable approach for the problem. The formulations derived here can consider the loads applied to the arbitrary locations of the shell elements. The second order rotations are additionally incorporated into the displacement field of an element and the combined effect with the present nonconservative loads is included. It is demonstrated that the nonconservative loads and the improved displacement field all contribute to the tangent stiffness matrix, by which beneficial effects on the convergence behavior can be expected. In the companion paper, the present theory successfully finds its good and important application in the analysis of prestressed concrete shell structure under nonconservative loads. It will be seen in the companion paper that the proposed theory provides very efficient and accurate method for the realistic analysis of prestressed concrete shell structures under nonconservative follower loads.

In the preceding companion paper, a more advanced theory for the geometrically nonlinear finite element(FE) analysis of the shell structures under eccentric follower loads has been carefully established. It is expected that the derived formulation can be applied realistically to wide range of practical problems. As an important application of the present theories, the numerical procedures for FE analysis of prestressed concrete(PSC) shell structures considering tendon-induced nonconservative loads are presented in this paper. The equivalent load approach is employed to implement the effect of prestressing tendon. The characteristics of the equivalent external load by the tendon are discussed and rigorously formulated into the load correction stiffness matrix(LCSM). It is found that the present numerical procedures can predict correctly the geometrically nonlinear response of the PSC shell structures up to the large deformations with the apparent contribution of the derived tangent stiffness matrices. Numerical examples of PSC shell structures are presented to demonstrate the applicability and validity of the proposed method. The present study allows more realistic and accurate analysis of shell structures which are subjected to nonconservative follower loads by exhibiting much faster convergence even for the relatively high load factors compared to the conventional method without the LCSM.

In the finite element(FE) analysis of prestressed concrete shell structures, several automatic generation schemes have been proposed to accommodate the geometry-related inputs of tendons especially for large FE models. The previously proposed algorithms established well basic procedures of the automatic generation. However, some deficiencies are found in those studies and there are some crude sub-algorithms which can decrease the speed of the procedure. The purpose of this study is, therefore, to propose some efficient methods which can improve the capability of the existing automatic generation algorithm in prestressed concrete shell structures. The efficient techniques are proposed here to accelerate the generation procedure and overcome the singular cases. The parametric representations of each shell element and a tendon, which are obtained by interpolating the given points, are used to develop the proposed algorithm. A numerical example is presented to verify the effectiveness of the proposed scheme. The proposed algorithm allows faster and more effective generation of tendon geometries for the efficient FE analysis of prestressed concrete shell structures.