Numerical investigation of non-linear deflections of an infinite beam on non-linear and discontinuous elastic foundation

The analysis of static deflections of an infinite beam resting on a non-linear and discontinuous foundation is not trivial. We apply a recently proposed iterative non-linear procedure to the analysis. Mathematical models of the elastic foundation are incorporated into the governing non-linear fourth-order differential equation of the system and then the differential equation is transformed into an equivalent non-linear integral equation using Green's functions. Numerical solutions of the integral equation clearly demonstrate herein that our non-linear iterative numerical method is simple and straightforward for approximate solutions of the static deflection of an infinite beam on a non-linear elastic foundation. Iterative numerical solutions converge fast to corresponding analytic solutions. However, numerical errors are observed in a narrow neighbourhood of material discontinuities of foundations

A Reaction Between High Mn-High Al Steel and CaO-SiO2-Type Molten Mold Flux: Part I. Composition Evolution in Molten Mold Flux

In order to elucidate the reaction mechanism between high Mn-high Al steel such as twin-induced plasticity steel and molten mold flux composed mainly of CaO-SiO2 during continuous casting process, a series of laboratory-scale experiments were carried out in the present study. Molten steel and molten flux were brought to react in a refractory crucible in a temperature range between 1713 K to 1823 K (1440 A degrees C to 1550 A degrees C) and composition evolution in the steel and the flux was analyzed using inductively coupled plasma atomic emission spectroscopy, X-ray fluorescence, and electron probe microanalysis. The amount of SiO2 in the flux was significantly reduced by Al in the steelthus, Al2O3 was accumulated in the flux as a result of a chemical reaction, 4[Al] + 3(SiO2) = 3[Si] + 2(Al2O3). In order to find a major factor which governs the reaction, a number of factors ((pct CaO/pct SiO2), (pct Al2O3), [pct Al], [pct Si], and temperature) were varied in the experiments. It was found that the above chemical reaction was mostly governed by [pct Al] in the molten steel. Temperature had a mild effect on the reaction. On the other hand, (pct CaO/pct SiO2), (pct Al2O3), and [pct Si] did not show any noticeable effect on the reaction. Apart from the above reaction, the following reactions are also thought to happen simultaneously: 2[Mn] + (SiO2) = [Si] + 2(MnO) and 2[Fe] + (SiO2) = [Si] + 2(FeO). These oxide components were subsequently reduced by Al in the molten steel. Na2O in the molten flux was gradually decreased and the decrease was accelerated by increasing [pct Al] and temperature. Possible reactions affecting the Al2O3 accumulation are summarized.ope

Presumed pseudokinase VRK3 functions as a BAF kinase

Vaccinia-related kinase 3 (VRK3) is known as a pseudokinase that is catalytically inactive due to changes in motifs that are essential for kinase activity. Although VRK3 has been regarded as a genuine pseudokinase from structural and biochemical studies, recent reports suggest that VRK3 acts as an active kinase as well as a signaling scaffold in cells. Here, we demonstrate that VRK3 phosphorylates the nuclear envelope protein barrier-to-autointegration factor (BAF) on Ser4. Interestingly, VRK3 kinase activity is dependent upon its N-terminal regulatory region, which is excluded from the determination of its crystal structure. Furthermore, the kinase activity of VRK3 is involved in the regulation of the cell cycle. VRK3 expression levels increase during interphase, whereas VRK1 is enriched in late G2 and early M phase. Ectopic expression of VRK3 induces the translocation of BAF from the nucleus to the cytoplasm. In addition, depletion of VRK3 decreases the population of proliferating cells. These data suggest that VRK3-mediated phosphorylation of BAF may facilitate DNA replication or gene expression by facilitating the dissociation of nuclear envelope proteins and chromatin during interphase. (C) 2015 Elsevier B.V. All rights reserved.1174Ysciescopu

Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice

Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-allylic positions substantially decreases the overall rate of ARA oxidation when hydrogen abstraction is an initiating event. To compare the effects of dosing of arachidonic acid (H-ARA) and its bis-allylic hexadeuterated form (D-ARA) on lungs in conventionally healthy mice and in an acute lung injury model, mice were dosed with H-ARA or D-ARA for six weeks through dietary supplementation and then challenged with intranasal lipopolysaccharide (LPS) for subsequent analysis of bronchoalveolar lavage fluid and lung tissue. Dosing on D-ARA resulted in successful incorporation of D-ARA into various tissues. D-ARA significantly reduced LPS-induced adverse effects on alveolar septal thickness and the bronchoalveolar area. Oral deuterated ARA is taken up efficiently and protects against adverse LPS-induced pathology. This suggests novel therapeutic avenues for reducing lung damage during severe infections and other pathological conditions with inflammation in the pulmonary system and other inflammatory diseases

Multi-length scale microstructural design of lithium-ion battery electrodes for improved discharge rate performance

Fast discharge capability of automotive batteries not only affects the acceleration and climbing performance of electric vehicles, but also the accessible driving range under complex driving cycles. Understanding the intricate physical and chemical processes across multiple length-scales is critical to assist the strategic design of electrodes for improved rate performance. Here, we correlate the discharge rate performance of Ni-rich LiNi1−x−yCoxMnyO2 (NMC) cathodes to the electrode architectures, ranging from the crystallographic orientations, surface morphology and cracks at single particle level, to the factors that affect the dominance of the solid and liquid-state transport (SST and LST) at electrode level. A random orientation of the primary particles is found to incur an increase of the SST resistance by a factor of 2.35 at 5C and a heterogeneous intra-particle lithiation. Internal cracks significantly restrict the accessibility to the active material. Double-layered particles are proved to be a more promising candidate than single-crystal particles. At electrode level, the SST-dominance depth is quantified for the first time to guide the microstructural tuning and rational operating windows are proposed for electrodes of various architectures. The reaction front is observed to shuttle across the electrode depth to mitigate the polarization, which can provide valuable insights into the battery management development. Finally, by comparing the performance of single crystal and polycrystalline NMC811 electrodes, it is suggested that electrode thickness and porosity are more critical in the former for enhanced discharge rate performance, in contrast to polycrystalline electrodes, in which a gradient particle fraction and size distribution are recommended

Women’s experiences of wearing therapeutic footwear in three European countries

Background: Therapeutic footwear is recommended for those people with severe foot problems associated with rheumatoid arthritis (RA). However, it is known that many do not wear them. Although previous European studies have recommended service and footwear design improvements, it is not known if services have improved or if this footwear meets the personal needs of people with RA. As an earlier study found that this footwear has more impact on women than males, this study explores women’s experiences of the process of being provided with it and wearing it. No previous work has compared women’s experiences of this footwear in different countries, therefore this study aimed to explore the potential differences between the UK, the Netherlands and Spain. Method: Women with RA and experience of wearing therapeutic footwear were purposively recruited. Ten women with RA were interviewed in each of the three countries. An interpretive phenomenological approach (IPA) was adopted during data collection and analysis. Conversational style interviews were used to collect the data. Results: Six themes were identified: feet being visibly different because of RA; the referring practitioners’ approach to the patient; the dispensing practitioners’ approach to the patient; the footwear being visible as different to others; footwear influencing social participation; and the women’s wishes for improved footwear services. Despite their nationality, these women revealed that therapeutic footwear invokes emotions of sadness, shame and anger and that it is often the final and symbolic marker of the effects of RA on self perception and their changed lives. This results in severe restriction of important activities, particularly those involving social participation. However, where a patient focussed approach was used, particularly by the practitioners in Spain and the Netherlands, the acceptance of this footwear was much more evident and there was less wastage as a result of the footwear being prescribed and then not worn. In the UK, the women were more likely to passively accept the footwear with the only choice being to reject it once it had been provided. All the women were vocal about what would improve their experiences and this centred on the consultation with both the referring practitioner and the practitioner that provides the footwear. Conclusion: This unique study, carried out in three countries has revealed emotive and personal accounts of what it is like to have an item of clothing replaced with an ‘intervention’. The participant’s experience of their consultations with practitioners has revealed the tension between the practitioners’ requirements and the women’s ‘social’ needs. Practitioners need greater understanding of the social and emotional consequences of using therapeutic footwear as an intervention

Minimization of phonon-tunneling dissipation in mechanical resonators

Micro- and nanoscale mechanical resonators have recently emerged as ubiquitous devices for use in advanced technological applications, for example in mobile communications and inertial sensors, and as novel tools for fundamental scientific endeavors. Their performance is in many cases limited by the deleterious effects of mechanical damping. Here, we report a significant advancement towards understanding and controlling support-induced losses in generic mechanical resonators. We begin by introducing an efficient numerical solver, based on the "phonon-tunneling" approach, capable of predicting the design-limited damping of high-quality mechanical resonators. Further, through careful device engineering, we isolate support-induced losses and perform the first rigorous experimental test of the strong geometric dependence of this loss mechanism. Our results are in excellent agreement with theory, demonstrating the predictive power of our approach. In combination with recent progress on complementary dissipation mechanisms, our phonon-tunneling solver represents a major step towards accurate prediction of the mechanical quality factor.Comment: 12 pages, 4 figure

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease

Self-activated ultrahigh chemosensitivity of oxide thin film nanostructures for transparent sensors

One of the top design priorities for semiconductor chemical sensors is developing simple, low-cost, sensitive and reliable sensors to be built in handheld devices. However, the need to implement heating elements in sensor devices, and the resulting high power consumption, remains a major obstacle for the realization of miniaturized and integrated chemoresistive thin film sensors based on metal oxides. Here we demonstrate structurally simple but extremely efficient all oxide chemoresistive sensors with similar to 90% transmittance at visible wavelengths. Highly effective self-activation in anisotropically self-assembled nanocolumnar tungsten oxide thin films on glass substrate with indium-tin oxide electrodes enables ultrahigh response to nitrogen dioxide and volatile organic compounds with detection limits down to parts per trillion levels and power consumption less than 0.2 microwatts. Beyond the sensing performance, high transparency at visible wavelengths creates opportunities for their use in transparent electronic circuitry and optoelectronic devices with avenues for further functional convergence.open181

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed