Clinical applications of transient elastography

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan®) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice

Consensus of Corporate E-Learning System Stakeholders Regarding the Satisfaction of End-Users

The purpose of this study is to call attention to the consensus of stakeholders of corporate e-Learning system regarding success. We identified the critical success factors (contents, technical features, management, and organizational support) as major components of corporate eLearning systems and questioned whether stakeholders’ consensus on the importance of these components facilitates the implementation of these components to achieve good quality or well. We also questioned whether the influence of these components on user satisfaction could be moderated by contextual factors. Based on empirical testing of 18 eLearning user companies, we verified that the consensus of stakeholders regarding the importance of content, technological features, and organizational support has a positive influence on the perceived quality of these factors in their e-Learning systems, which in turn is positively related to user satisfaction. The learning subjects and learning style did significantly moderate the influences of these perceived qualities on user satisfaction

Plastic Shrinkage Properties of Natural Fiber Reinforced Shotcrete

Recently, natural hemp fibers have been developed for use in wet or dry mix shotcrete instead of conventional synthetic fibers made from petroleum. Synthetic fibers, which is mainly in polypropylene, has been used for controlling an initial shrinkage cracking in concrete, however, the effect was poor showing a severe plastic shrinkage cracking. Plastic shrinkage cracking is a nonstructural crack that occurs due to the surface drying of concrete in a plastic condition due to rapid evaporation of bleeding water. The volume reduction due to plastic shrinkage and the resulting tensile stress exceeds the tensile strength of the concrete. In particular, plastic shrinkage cracking occurs mainly in large surface area members. It may be evolved from the surface to a considerable depth, or in the case of a very thin structure, it may go all over the depth of the member. In addition, since it is long enough to be easily distinguished by naked eyes and cracks are generated widely, it is not aesthetically pleasing and anxiety about the stability of the concrete can be increased. Also, the plastic shrinkage crack accelerates penetration of chloride and moisture, causing corrosion of the reinforcing bar, and durability of the concrete is lowered. The theoretical effect of natural fibers on plastic shrinkage cracks is that when natural fibers are mixed into concrete, they become wet by absorbing the water. Then, in the pumping, water in the wet natural fiber is supplied to the concrete by the pumping pressure to increase the pumpability. Re-absorbing the water after spraying increases the adhesion and build-up thickness. The absorbed water could be supplied to the shotcrete and resulted in reducing a plastic shrinkage and dry shrinkage. This paper investigates the plastic shrinkage properties of shotcrete containing natural fibers. A series of experimental program were conducted to analysis the theoretical background and to select the optimized natural fiber content

Targeting Mannitol Metabolism as an Alternative Antimicrobial Strategy Based on the Structure-Function Study of Mannitol-1-Phosphate Dehydrogenase in Staphylococcus aureus

Mannitol-1-phosphate dehydrogenase (M1PDH) is a key enzyme in Staphylococcus aureus mannitol metabolism, but its roles in pathophysiological settings have not been established. We performed comprehensive structure-function analysis of M1PDH from S. aureus USA300, a strain of community-associated methicillin-resistant S. aureus, to evaluate its roles in cell viability and virulence under pathophysiological conditions. On the basis of our results, we propose M1PDH as a potential antibacterial target. In vitro cell viability assessment of ΔmtlD knockout and complemented strains confirmed that M1PDH is essential to endure pH, high-salt, and oxidative stress and thus that M1PDH is required for preventing osmotic burst by regulating pressure potential imposed by mannitol. The mouse infection model also verified that M1PDH is essential for bacterial survival during infection. To further support the use of M1PDH as an antibacterial target, we identified dihydrocelastrol (DHCL) as a competitive inhibitor of S. aureus M1PDH (SaM1PDH) and confirmed that DHCL effectively reduces bacterial cell viability during host infection. To explain physiological functions of SaM1PDH at the atomic level, the crystal structure of SaM1PDH was determined at 1.7-Å resolution. Structure-based mutation analyses and DHCL molecular docking to the SaM1PDH active site followed by functional assay identified key residues in the active site and provided the action mechanism of DHCL. Collectively, we propose SaM1PDH as a target for antibiotic development based on its physiological roles with the goals of expanding the repertory of antibiotic targets to fight antimicrobial resistance and providing essential knowledge for developing potent inhibitors of SaM1PDH based on structure-function studies.IMPORTANCE Due to the shortage of effective antibiotics against drug-resistant Staphylococcus aureus, new targets are urgently required to develop next-generation antibiotics. We investigated mannitol-1-phosphate dehydrogenase of S. aureus USA300 (SaM1PDH), a key enzyme regulating intracellular mannitol levels, and explored the possibility of using SaM1PDH as a target for developing antibiotic. Since mannitol is necessary for maintaining the cellular redox and osmotic potential, the homeostatic imbalance caused by treatment with a SaM1PDH inhibitor or knockout of the gene encoding SaM1PDH results in bacterial cell death through oxidative and/or mannitol-dependent cytolysis. We elucidated the molecular mechanism of SaM1PDH and the structural basis of substrate and inhibitor recognition by enzymatic and structural analyses of SaM1PDH. Our results strongly support the concept that targeting of SaM1PDH represents an alternative strategy for developing a new class of antibiotics that cause bacterial cell death not by blocking key cellular machinery but by inducing cytolysis and reducing stress tolerance through inhibition of the mannitol pathway

Observation of First-Order Metal-Insulator Transition without Structural Phase Transition in VO_2

An abrupt first-order metal-insulator transition (MIT) without structural phase transition is first observed by current-voltage measurements and micro-Raman scattering experiments, when a DC electric field is applied to a Mott insulator VO_2 based two-terminal device. An abrupt current jump is measured at a critical electric field. The Raman-shift frequency and the bandwidth of the most predominant Raman-active A_g mode, excited by the electric field, do not change through the abrupt MIT, while, they, excited by temperature, pronouncedly soften and damp (structural MIT), respectively. This structural MIT is found to occur secondarily.Comment: 4 pages, 4 figure