A validated thermal model of bead-on-plate welding

In this paper, finite element model is used to carry out thermal analysis of bead-on-plate welding. The model followed the proposed five step strategies which were then built into a model to obtain temperature history at the positions of thermocouples. Temperature field was also evaluated by comparing predicted weld bead with the actual weld bead. Using these proposed strategies, well matched temperature histories and temperature field have been obtained

Friction and asperity contact in strip rolling

This paper reviews different aspects of friction and asperity contacts in strip rolling. The mixed film lubrication model considers the effect of asperity flattening and the lubrication within the working zone. The oil concentration of the emulsion at entry and throughout the roll bite is considered together with the thermal effects of the contacts. The actual area of contact due to asperity deformation can be determined from a 3-wavelength FEM model. The deformation of a randomly generated surface of the hot strip with oxide scale can also be modeled by an FEM method. The friction variation in the roll bite can be determined by a sensor roll, and the average friction determined from the forward slip by the marking method or laser Doppler method. The friction models in FEM modeling are also discussed

Agency in Transport Service: Implications of Traveller Mode Choice Objective and Latent Attributes Using Random Parameter Logit Model

Abstract: This paper explains how principal-agent theory (PAT) can be used as an analytical tool to understand the traveller-Transport for NSW (TfNSW) relationship and minimise the agency problem in the relationship by examining traveller preferences for mode choices. The paper emphasises latent variables (LVs) and traditional objective attributes (TOAs) together during the choice process within the agency relationship, as a method by which the utility of the principal (traveller) can be maximised and evaluated using a discrete choice experiment, i.e. random parameter logit (RPL) model. The probability of car use is significantly higher than public transport, which indicates that an agency problem exists in the relationship and incorporating traveller preferences in the transport projects may minimise this problem. Citation: Anwar, A.H.M., Tieu, K., Gibson, P., Win, K.T. & Berryman, M.J. (2014). Agency in Transport Service: Implications of Traveller Mode Choice Objective and Latent Attributes Using Ransom Parameter Logit Model. In: Campbell P. and Perez P. (Eds), Proceedings of the International Symposium of Next Generation Infrastructure, 1-4 October 2013, SMART Infrastructure Facility, University of Wollongong, Australia

Micromechanics of thin oxide scale and surface roughness transfer in hot metal rolling

The deformation micromechanics of the thin oxide scale formed in hot metal rolling and surface roughness transfer characterization are very important for the quality of the finished product. Finite element simulation of the thin oxide scale deformation and surface roughness transfer is carried out. Surface asperity deformation of the thin oxide scale and strip is focused. Surface characterisation and micromechanics of the thin oxide scale deformation are obtained from the finite element simulation and experimental measurements. Simulation results are close to the measured values. The forming features of surface roughness transfer during hot metal rolling with lubrication are also discussed

Asymmetric cryorolling for fabrication of nanostructural aluminum sheets

Nanostructural Al 1050 sheets were produced using a novel method of asymmetric cryorolling under ratios of upper and down rolling velocities (RUDV) of 1.1, 1.2, 1.3, and 1.4. Sheets were rolled to about 0.17 mm from 1.5 mm. Both the strength and ductility of Al 1050 sheets increase with RUDVs. Tensile strength of Al sheets with the RUDV 1.4 is larger 22.3% of that for RUDV 1.1, which is 196 MPa. The TEM observations show the grain size is 360 nm when the RUDV is 1.1, and 211 nm for RUDV 1.4

Local anesthetics induce autophagy in young permanent tooth pulp cells

Pulp cells are essential for tooth development, and dentin repair and regeneration. In addition these cells have been identified as an important stem cell source. Local anesthetics are widely used in dental clinics, as well as the other clinical disciplines and have been suggested to interfere with human permanent tooth development and induce tooth agenesis through unknown mechanisms. Using pig model and human young permanent tooth pulp cells, our research has identified that the local anesthetics commonly used in clinics can affect cell proliferation. Molecular pathway profiling suggested that LC3II is one of the earliest molecules induced by the agents and p62 is the only common downstream target identified for all the drugs tested. The effect of the drugs could be partially recovered by V-ATPase inhibitor only if early intervention is performed. Our results provide novel evidence that local anesthetics could affect tooth cell growth that potentially can have impacts on tooth development

Exosome release and neuropathology induced by α-synuclein: new insights into protective mechanisms of Drp1 inhibition

AbstractTargeting alpha-synuclein (α-syn) as a therapeutic strategy for Parkinson’s disease (PD) has been intensively pursued largely due to its well-recognized pathogenic role. Since its discovery as the first familial link to PD over two decades ago, this protein has been associated with multiple neurotoxic mechanisms, such as mitochondrial dysfunction and impaired autophagic flux. We report here that blocking dynamin-related protein 1 (Drp1) improved both mitochondrial function and autophagic flux in experimental models of α-syn. Using rat dopaminergic neuronal cells with inducible wild-type human α-syn, we observed excessive mitochondrial fragmentation and increased Drp1 levels 48 h after gene induction. Functionally, these cells exhibited lower mitochondrial membrane potential, reduced ATP production rate and mitochondrial spare respiratory capacity, as well as increased levels of mitochondrial reactive oxygen species. To evaluate the protective role of Drp1 inhibition, we used three complementary approaches: gene silencing mediated by siRNA, overexpression of Drp1-dominant negative and the small molecule mitochondrial division inhibitor-1 (mdivi-1). Both morphological and functional defects induced by α-syn were attenuated by these strategies. Importantly, Drp1 inhibition reduced proteinase K-resistant α-syn aggregates. Based on that observation, we investigated the involvement of autophagy. Through a combination of stable autophagy reporter cells and immunoreactivity for LC3 and p62 in neuronal cells with either α-syn overexpression or treatment of human α-syn preformed fibrils (PFF), we observed that Drp1 inhibition abolished autophagic impairment induced by α-syn. Consistent with its role in improving autophagy function, Drp1 inhibition reduced exosome release and spread of α-syn pathology from neurons to neurons and from microglia to neurons. In summary, this study highlights new insights that Drp1 inhibition confers neuroprotection through both mitochondrial and autophagy-lysosomal pathways, further strengthening the therapeutic potential of targeting Drp1.</jats:p

Asymmetric Cold Rolling of Thin Strip with Roll Edge Kiss

Asymmetric rolling can reduce the thickness of rolled strip and rolling load significantly. In this paper, the asymmetric cold rolling of thin strip with roll edge kiss was analysed theoretically and the rolling pressure, intermediate force between the work roll and backup roll, the work roll edge kiss force, the strip profile after rolling are obtained for this special asymmetric rolling. The rolling pressure, intermediate force, roll edge kiss force and the strip profile are compared for various roll speed ratios, reduction and friction coefficients. Simulation result shows that the roll speed ratio and reduction have significant influence on the profile of rolled strip, and the calculated rolling forces are consistent with the measured values. The effect of friction in the roll bite on mechanics of the asymmetric cold rolling of thin strip with roll edge kiss is also discussed

Endogenously produced nonclassical vitamin D hydroxy-metabolites act as "biased" agonists on VDR and inverse agonists on RORα and RORγ

The classical pathway of vitamin D activation follows the sequence D3→25(OH)D3→1,25(OH)(2)D3 with the final product acting on the receptor for vitamin D (VDR). An alternative pathway can be started by the action of CYP11A1 on the side chain of D3, primarily producing 20(OH)D3, 22(OH)D3, 20,23(OH)(2)D3, 20,22(OH)(2)D3 and 17,20,23(OH)(3)D3. Some of these metabolites are hydroxylated by CYP27B1 at C1α, by CYP24A1 at C24 and C25, and by CYP27A1 at C25 and C26. The products of these pathways are biologically active. In the epidermis and/or serum or adrenals we detected 20(OH)D3, 22(OH)D3, 20,22(OH)(2)D3, 20,23(OH)(2)D3, 17,20,23(OH)(3)D3, 1,20(OH)(2)D3, 1,20,23(OH)(3)D3, 1,20,22(OH)(3)D3, 20,24(OH)(2)D3, 1,20,24(OH)(3)D3, 20,25(OH)(2)D3, 1,20,25(OH)(3)D3, 20,26(OH)(2)D3 and 1,20,26(OH)(3)D3. 20(OH)D3 and 20,23(OH)(2)D3 are non-calcemic, while the addition of an OH at C1α confers some calcemic activity. Molecular modeling and functional assays show that the major products of the pathway can act as “biased” agonists for the VDR with high docking scores to the ligand binding domain (LBD), but lower than that of 1,25(OH)(2)D3. Importantly, cell based functional receptor studies and molecular modeling have identified the novel secosteroids as inverse agonists of both RORα and RORγ receptors. Specifically, they have high docking scores using crystal structures of RORα and RORγ LBDs. Furthermore, 20(OH)D3 and 20,23(OH)(2)D3 have been tested in cell model that expresses a Tet-on RORα or RORγ vector and a RORE-LUC reporter (ROR-responsive element), and in a mammalian 2-hybrid model that test interactions between an LBD-interacting LXXLL-peptide and the LBD of RORα/γ. These assays demonstrated that the novel secosteroids have ROR-antagonist activities that were further confirmed by the inhibition of IL17 promoter activity in cells overexpressing RORα/γ. In conclusion, endogenously produced novel D3 hydroxy-derivatives can act both as “biased” agonists of the VDR and/or inverse agonists of RORα/γ. We suggest that the identification of large number of endogenously produced alternative hydroxy-metabolites of D3 that are biologically active, and of possible alternative receptors, may offer an explanation for the pleiotropic and diverse activities of vitamin D, previously assigned solely to 1,25(OH)(2)D3 and VDR