A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal {beta}-sandwich domain

Transglutaminase type 2 (TG2) catalyzes the formation of an -( -glutamyl)-lysine isopeptide bond between adjacent peptides or proteins including those of the extracellular matrix (ECM). Elevated extracellular TG2 leads to accelerated ECM deposition and reduced clearance that underlie tissue scarring and fibrosis. The extracellular trafficking of TG2 is crucial to its role in ECM homeostasis; however, the mechanism by which TG2 escapes the cell is unknown as it has no signal leader peptide and therefore cannot be transported classically. Understanding TG2 transport may highlight novel mechanisms to interfere with the extracellular function of TG2 as isoform-specific TG2 inhibitors remain elusive. Mammalian expression vectors were constructed containing domain deletions of TG2. These were transfected into three kidney tubular epithelial cell lines, and TG2 export was assessed to identify critical domains. Point mutation was then used to highlight specific sequences within the domain required for TG2 export. The removal of -sandwich domain prevented all TG2 export. Mutations of Asp94 and Asp97 within the N-terminal -sandwich domain were identified as crucial for TG2 externalization. These form part of a previously identified fibronectin binding domain (88WTATVVDQQDCTLSLQLTT106). However, siRNA knockdown of fibronectin failed to affect TG2 export. The sequence 88WTATVVDQQDCTLSLQLTT106 within the -sandwich domain of TG2 is critical to its export in tubular epithelial cell lines. The extracellular trafficking of TG2 is independent of fibronectin

Auto-disturbance-rejection controller for SVC to enhance wind farm voltage stability

Author name used in this publication: C. Y. ChungRefereed conference paper2008-2009 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Roles of social capital in tacit knowledge acquisition

Social capital has evolved from an interdisciplinary standpoint. Recently, interests over it have been instigated by entrepreneur literatures because of the arising need to understand its contribution to quality of resource-based management, specifically knowledge-based resources, which provides a great possibility for a successful firm performance. Nevertheless, knowledge and information, just like social capital, are multidimensional in sources and consequences. Scholars have differentiated between tacit and explicit knowledge to clearly present their argument that these two types of knowledge fit various networks of social relations for optimal performance. Therefore, an in-depth investigation of the correlation between social capital and tacit knowledge acquisition is essential to the establishment of a framework that would shed light on the implications of social relations in the corporate world

Challenges of simulating undrained tests using the constant volume method in DEM

Liquefaction during earthquakes can cause significant infrastructural damage and loss of life, motivating a fundamental study of undrained sand response using discrete element modeling (DEM). Two methods are widely used in DEM for simulating the undrained response of soil. One approach is to numerically couple the DEM code with a fluid model. Alternatively, if the soil is fully saturated and water is assumed to be incompressible, the volume of the sample can be held constant to simulate an undrained test. The latter has the advantage of being computationally straightforward, but the assumption of a constant volume can cause some issues which are discussed in this paper. Depending on the contact model selected, extremely high deviatoric stresses and pore water pressures can be generated for dense samples using the constant volume approach which are not observed in corresponding laboratory tests. Furthermore the results of these constant volume simulations tend to be sensitive to the strain rate selected. The evolution of particle size distribution caused by grain crushing is also ignored in most undrained simulations. For these reasons, authors often restrict the extent of the data presented to physically-realistic ranges and report results in non-dimensional terms, e.g., using stress ratios (q/p’) or stresses normalized by the initial confining pressure. This paper aims to highlight some of these issues, explore whether the constant volume approach is appropriate and make recommendations for future analysis of undrained soil behavior using DEM. © 2013 AIP Publishing LLCpublished_or_final_versio

Prognostic Value of 18 F-FDG PET-CT in Nasopharyngeal Carcinoma: Is Dynamic Scanning Helpful?

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Herpes zoster and its neurological complications

Ninety-three Chinese patients with cutaneous herpes zoster were seen during a 4-year period. Thoracic zoster occurred most commonly, followed by ophthalmic, cervical and lumbosacral zoster. Neurological complications were present in eleven patients (11.8%), the commonest being Ramsay-Hunt syndrome and segmental limb paresis. The clinical picture, pathogenesis, treatment and outcome of segmental limb paresis, myelitis and delayed contralateral hemiparesis following zoster ophthalmicus are discussed. Nine immunocompromised patients received intravenous adenine arabinoside (vidarabine) or acycloguanosine (acyclovir), and no cutaneous or visceral spread occurred in these patients.published_or_final_versio

Exploring the micro-mechanics of triaxial instability in granular materials

The instability of granular materials due to water infiltration under fully drained conditions has been previously considered in experimental studies. While laboratory experiments can provide macro-scale insight into drained instability, the micro-mechanics under such conditions are yet to be explored. This study has employed the discrete-element method (DEM) to simulate constant shear drained (CSD) tests for an ideal soil. CSD tests were initiated from a range of packing densities and stress conditions. The DEM simulations were able to qualitatively replicate laboratory CSD tests. The choice of the loading control parameter was seen to play a central role in the macro-scale second-order work to identify an effective failure. All samples considered attained an onset of instability that coincided with fluctuations in the second-order work from a particle scale. The time of occurrence of the onset of instability was seen to depend on initial packing density and stress state. A change in the evolution of macro- and micro-mechanical quantities, showing either a sharp increase or decrease, was observed once the CSD conditions had been reached. Finally, conventional drained then constant volume (CDCV) tests were carried out where the appearance of instabilities and the evolution of macro and micro quantities were found to be different from those observed in CSD tests. The results presented in this study indicate that the constant shear drained loading conditions can result in more unfavourable situations than for the undrained loading condition

RhoGDI beta-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK

[[abstract]]We found that overexpression of RhoGDI beta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDI beta expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDI beta physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDI beta functions. Moreover, the ZAK-RhoGDI beta interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDI beta functions through phosphorylation and RhoGDI beta counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDI beta-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDI beta

Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition

Showing A quantification of GFP-positive cells in the lung after intravenous injection of MKPCs in five-sixths nephrectomized mice (y axis shows the number of cells, while the x axis (FL1-H) shows the fluorescence intensity; M1 is the area of GFP-positive cells) and B immunohistochemistry of the lung after intravenous injection of MKPCs into a mouse that underwent five-sixths nephrectomy. Few GFP positive cells were found in the lung at the first day but there were no GFP-positive cells at week 14. (TIFF 2253 kb

Effects of inter-particle friction on the critical state behaviour of granular materials: a numerical study

The Conference program's website is located at http://congress.cimne.com/particles2013/frontal/ProgTodo.aspTechnical Session: IS - Instability Mechanisms: From Particles to Structures II (Invited Session)ECCOMAS Thematic Conference SeriesCritical state soil mechanics (CSSM) gives a theoretical framework for soil modelling. This paper investigates the effect of inter-particle friction on the critical state behavior of DEM assemblies with grading representative of a real soil. It is found that the angle of shearing resistance at the critical state increases with increasing inter-particle friction () and in void ratio (e) vs logarithmic mean effective stress (log(p’)) space the critical state locii have higher e values when is higher. An atypical CSL in e-logp’ space that deviates from experimental observations and the classical CSSM behavior was observed when µ = 0.5. Micro-scale analyses show that this can be attributed to the emergence of a higher number of floating particles due to the increasing self-stability of strong force chains with increasing inter-particle friction. This study recommends the use of inter-particle friction lower than 0.5 in DEM simulations of element testing in soil mechanics.published_or_final_versio