Existence and asymptotic behavior of C1C^1 solutions to the multidimensional compressible Euler equations with damping

In this paper, the existence and asymptotic behavior of $C^1$ solutions to the multidimensional compressible Euler equations with damping on the framework of Besov space are considered. We weaken the regularity requirement of the initial data, and improve the well-posedness results of Sideris-Thomases-Wang (Comm.P.D.E. 28 (2003) 953). The global existence lies on a crucial a-priori estimate which is proved by the spectral localization method. The main analytic tools are the Littlewood-Paley decomposition and Bony's para-product formula.Comment: 18 page

Structural and Biochemical Studies of Glyoxylate Shunt Enzymes as Drug Targets of Mycobacterium tuberculosis

As the world population battles drug-resistant tuberculosis (TB), there is an urgent need for novel anti-tubercular drugs. This dissertation documents the studies of glyoxylate shunt enzymes, isocitrate lyase (ICL) and malate synthase (GlcB), in Mycobacterium tuberculosis (Mtb) as drug targets for the therapeutic development of TB. Two different drug discovery approaches were used. A mechanism based approach was utilized for isocitrate lyase, while a fragment based approach was applied for malate synthase, and both approaches employed X-ray crystallography as a primary technique. Through the mechanism based approach, an ICL inhibitor complexed crystal structure was solved to 2.6 Å resolution after the treatment with itaconate. From the structure, the active site cysteine (Cys191) underwent covalent modification to form an S-methylsuccinyl adduct. The inhibitory mechanism was based on the direct nucleophilic attack on the itaconate vinyl group by Cys191 after activation via a nearby general base. Additional crystal structure of ICL following the inactivation by 2-vinyl isocitrate (2-VIC) at 1.8 Å resolution confirmed the formation of an S-homopyruvoyl adduct of Cys191. The structure was consistent with the proposed inhibitory mechanism where 2-VIC first bound in the active site in the same manner as the substrate isocitrate. A base catalyzed aldo cleavage of the C2-C3 bond of 2-VIC then produced 2-vinyl glyoxylate and the aci-succinate. Cys191 was deprotonated to generate succinate, as in the lyase mechanism, followed by the Michael addition of Cys191 thiolate to 2-vinyl glyoxylate to form the final S-homopyruoyl adduct. A fragment based approach was used to advance drug discovery and further probe the active site of Mtb GlcB. Two libraries of 1580 fragments were screened against GlcB using differential scanning fluorimetry (DSF) to identify binding hits, and 18 complexed crystal structures were solved at 1.9-2.5 Å resolutions. The fragment bound GlcB crystal structures captured the conformations of the active site, which have not been reported for Mtb GlcB. The movements of two loops around the active site gave rise to a second portal to the surface and the narrowing of the active site tunnel. This series of conformational changes was hypothesized as a pathway for substrate-product exchange. The structures of the enzyme at various stages of product formation and dissociation, as well as an apo enzyme structure, were further elucidated to confirm the hypothesis. As a result, a detailed, mechanism driven substrate-product exchange in catalysis was formulated. One novel interaction from the fragments and the enzyme was further incorporated into the existing phenyl-diketo acid (PDKA) inhibitor, providing new drug designs. The resulting lead molecule was 100 times more potent compared to the parent PDKA, and was shown to make the same interaction and induce the same movement in the active site as the original fragment. The comprehensive knowledge from the structural studies of the two glyoxylate shunt enzymes provided new information that could lead to a greater understanding of Mtb’s physiology and guide the discovery of more effective treatments of TB

Enunciative identity in elementary English as a foreign language

How to improve the skill of speaking English is a major challenge for English learners in Taiwan nowadays. This project focuses on issues of pronunciation as the starting point to examine the problems of learning English, and issues of identity transformation in the language-learning process. Then it addresses the concept of enunciation as a way to facilitate English learners to establish their confidence in, and ownership of, the target language. This project is designed not only for discussing issues of improving the teaching and learning of English pronunciation, but also for explicating how students can gain their own voices and define their subjectivity during their English-learning process

Social Capital, Rehabilitation, Tradition: Support for Restorative Justice in Japan and Australia

This paper investigates the attitudes and beliefs that the public hold about criminal behaviour in Japanese and Australian society, with a view to uncovering sources of resistance to, and support for, restorative justice. The study draws on a survey of 1,544 respondents from Japan and 1,967 respondents from Australia. In both societies, restorative justice met with greater acceptance among those who were (1) strong in social capital, (2) believed in offender reintegration and rehabilitation, (3) saw benefits for victims in forgiveness, and (4) were advocates for victims' voices being heard and amends made. The alternative 'just deserts' and deterrence models for dealing with crime were grounded in attitudes of punitiveness and fear of moral decay, and reservations about the value of reintegrating and rehabilitating offenders. Like restorative justice supporters, 'just deserts' and deterrence supporters expressed concern that victims' voices be heard and amends made. Winning public support for competing institutional arrangements may depend on who does best in meeting expectations for meeting the needs of victims

Micromechanical Simulations of Heart Valve Tissues

Heart valve disease is generally treated by surgical replacement with either a mechanical or bioprosthetic valve. While prosthetic valves perform remarkably well, having significantly reduced patient mortality since their inception in 1960, each type exhibits specific drawbacks. Specifically, thrombosis and anticoagulation in the case of mechanical valves; calcific and fatigue-related degeneration in bioprosthetic heart valve (BHV). In attempt to improve the durability of BHV, recent studies have focused on quantifying the biomechanical interactions between the organ, tissue, and cellular-level components in native heart valve and BHV tissues. Such data is considered fundamental to designing improved BHV, and ultimately may be useful in the design of tissue engineered heart valves (TEHV).The goals of this research were two-fold: (1) to simulate layer-specific mechanical property changes incurred by the porcine BHV with fatigue, and (2) to simulate the cellular-level deformation of valve interstitial cells (VIC) nuclei under organ-level transvalvular pressures. For the first goal, parametric studies were conducted to isolate the effective modulii of the individual layers using finite element simulations of native and BHV tissues in flexure. The finite element simulations isolated fatigue-related changes in the overall effective modulus of BHV tissues specifically to the collagen-rich fibrosa layer. These results may be useful in designing improved BHV, as novel fixatives and fixation methods may have the capacity to target specific layers of the BHV tissue. For the second goal, cellular-level VIC nuclei deformations were quantified experimentally by analyzing images of histological sections prepared from native porcine aortic valves subjected to transvalvular pressures. Finite element simulations were conducted to quantify the relationship between organ-level transvalvular pressure, concomitant tissue-level strain, and ultimate cellular-level VIC nuclei deformation. The cellular-level image analysis studies uncovered layer-specific, positive relationships between VIC nuclei deformations and transvalvular pressure. These data were found to correlate with previously published data on the associated collagen fiber architecture, providing insight into the tissue-to-cellular level mechanical coupling predicted by the finite element simulations. These results may be useful in designing TEHV, as evidence suggests that the secretion and organization of extracellular matrix (ECM) (e.g., collagen) by the constituent cells of a TEHV can be modulated by mechanical deformation.To the best of our knowledge, the simulations presented herein represent the first attempt to quantify layer-specific changes in porcine BHV tissue mechanical properties with fatigue. Moreover, we report the first information on the cellular-level deformation of VIC nuclei under transvalvular pressures, including experimental analysis of the native porcine aortic valve, as well as rigorous finite element simulations. These micromechanical simulations thus offer new data on the biomechanical behavior of heart valve tissues, and may contribute to the design of improved BHV and TEHV