Constitutive model for localized Lüders-like stress-induced martensitic transformation and super-elastic behaviors of laser-welded NiTi wires

The application of the shape memory alloy NiTi in micro-electro-mechanical-systems (MEMSs) is extensive nowadays. In MEMS, complex while precise motion control is always vital. This makes the degradation of the functional properties of NiTi during cycling loading such as the appearance of residual strain become a serious problem to study, in particular for laser micro-welded NiTi in real applications. Although many experimental efforts have been put to study the mechanical properties of laser welded NiTi, surprisingly, up to the best of our understanding, there has not been attempts to quantitatively model the laser-welded NiTi under mechanical cycling in spite of the accurate prediction required in applications and the large number of constitutive models to quantify the thermo-mechanical behavior of shape memory alloys. As the first attempt to fill the gap, we employ a recent constitutive model, which describes the localized SIMT in NiTi under cyclic deformation; with suitable modifications to model the mechanical behavior of the laser welded NiTi under cyclic tension. The simulation of the model on a range of tensile cyclic deformation is consistent with the results of a series of experiments. From this, we conclude that the plastic deformation localized in the welded regions (WZ and HAZs) of the NiTi weldment can explain most of the extra amount of residual strain appearing in welded NiTi compared to the bare one. Meanwhile, contrary to common belief, we find that the ability of the weldment to memorize its transformation history, sometimes known as ‘return point memory’, still remains unchanged basically though the effective working limit of this ability reduces to within 6% deformation.

1-D constitutive model for evolution of stress-induced R-phase and localized Lüders-like stress-induced martensitic transformation of super-elastic NiTi wires

NiTi alloys have been widely used in the applications for micro-electro-mechanical-systems (MEMS), which often involve some precise and complex motion control. However, when using the NiTi alloys in MEMS application, the main problem to be considered is the degradation of functional property during cycling loading. This also stresses the importance of accurate prediction of the functional behavior of NiTi alloys. In the last two decades, a large number of constitutive models have been proposed to achieve the task. A portion of them focused on the deformation behavior of NiTi alloys under cyclic loading, which is a practical and non-negligible situation. Despite of the scale of modeling studies of the field in NiTi alloys, two experimental observations under uniaxial tension loading have not received proper attentions. First, a deviation from linearity well before the stress-induced martensitic transformation (SIMT) has not been modeled. Recent experiments confirmed that it is caused by the formation of stress-induced R phase. Second, the influence of the well-known localized Lüders-like SIMT on the macroscopic behavior of NiTi alloys, in particular the residual strain during cyclic loading, has not been addressed. In response, we develop a 1-D phenomenological constitutive model for NiTi alloys with two novel features: the formation of stress-induced R phase and the explicit modeling of the localized Lüders-like SIMT. The derived constitutive relations are simple and at the same time sufficient to describe the behavior of NiTi alloys. The accumulation of residual strain caused by R phase under different loading schemes is accurately described by the proposed model. Also, the residual strain caused by irreversible SIMT at different maximum loading strain under cyclic tension loading in individual samples can be explained by and fitted into a single equation in the proposed model. These results show that the proposed model successfully captures the behavior of R phase and the essence of localized SIMT.

Parameter estimation and equation formulation in Business Dynamics

System Dynamics enables modelling and simulation of highly non-linear feedback systems to predict future system behaviour. Parameter estimation and equation formulation are techniques in System Dynamics, used to retrieve the values of parameters or the equations for ?ows and/or variables. These techniques are crucial for the annotations and thereafter the simulation. This paper critically examines existing and well established approaches in parameter estimation and equation formulation along with their limitations, identifying performance gaps as well as providing directions for potential future research.

Development of an objective structured clinical examination (OSCE) to assess formulation and extemporaneous dispensing skills in MPharm undergraduates

Background: The use of Objective Structured Clinical Examination (OSCE) in Pharmacy has been explored; however this is the first attempt in Queen’s University School of Pharmacy, Belfast to assess students via this method in a module where chemistry is the main discipline.

Aims: To devise an OSCE to assess undergraduate ability to check extemporaneously dispensed products for clinical and formulation errors. This activity also aims to consider whether it is a viable method of assessment in such a science-based class, from a staff and student perspective.

Method: Students rotated around a number of stations, performing a check of the product, corresponding prescription and formulation record sheet detailing the theory behind the formulation. They were assessed on their ability to spot intentional mistakes at each one.

Results: Of the 79 students questioned, 95% indicated that OSCE made them aware of the importance of the clinical check carried out by the pharmacist. Nearly all of the undergraduates (72 out of 79) felt that OSCE made them aware of the type of mistakes that students make in class. Most (5 out of 7) of the academic team members strongly agreed that it made students aware of ‘point of dispensing’ checks carried out by pharmacists, in addition to helping them to prepare for their exam.

Conclusion: OSCE assesses both scientific and formulation skills, and has increased the diversity of assessment of this module, bringing with it many additional benefits for the undergraduates since it measures their ability to exercise professional judgement in a time- constrained environment and, in this way, mirrors the conditions many pharmacists work within.

Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation

Squamous cell carcinoma accounts for 20% of all human lung cancers and is strongly linked to cigarette smoking. It develops through premalignant changes that are characterized by high levels of keratin 14 (K14) expression in the airway epithelium and evolve through basal cell hyperplasia, squamous metaplasia and dysplasia to carcinoma in situ and invasive carcinoma. In order to explore the impact of K14 in the pulmonary epithelium that normally lacks both squamous differentiation and K14 expression, human keratin 14 gene hK14 was constitutively expressed in mouse airway progenitor cells using a mouse Clara cell specific 10 kDa protein (CC10) promoter. While the lungs of CC10-hK14 transgenic mice developed normally, we detected increased expression of K14 and the molecular markers of squamous differentiation program such as involucrin, loricrin, small proline-rich protein 1A, transglutaminase 1 and cholesterol sulfotransferase 2B1. In contrast, wild-type lungs were negative. Aging CC10-hK14 mice revealed multifocal airway cell hyperplasia, occasional squamous metaplasia and their lung tumors displayed evidence for multidirectional differentiation. We conclude that constitutive expression of hK14 initiates squamous differentiation program in the mouse lung, but fails to promote squamous maturation. Our study provides a novel model for assessing the mechanisms of premalignant lesions in vivo by modifying differentiation and proliferation of airway progenitor cells. © The Author 2008. Published by Oxford University Press. All rights reserved.

Synergistic effects on gene delivery - co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000 (TM)

This paper describes the application of gene delivery vectors based on connecting together two well-defined low-generation poly(L-lysine) (PLL) dendrons using a disulfide-containing linker unit. We report that the transfection ability of these vectors in their own right is relatively low, because the low-generation number limits the endosomal buffering capacity. Importantly, however, we demonstrate that when applied in combination with Lipofectamine 2000 (TM), a vector from the cationic lipid family, these small cationic additives significantly enhance the levels of gene delivery (up to four-fold). Notably, the cationic additives have no effect on the levels of transfection observed with a cationic polymer, such as DEAE dextran. We therefore argue that the synergistic effects observed with Lipofectamine 2000 (TM) arise as a result of combining the delivery advantages of two different classes of vector within a single formulation, with our dendritic additives providing a degree of pH buffering within the endosome. As such, the data we present indicate that small dendritic structures, although previously largely overlooked for gene delivery owing to their inability to transfect in their own right, may actually be useful well-defined additives to well-established vector systems in order to enhance the gene delivery payload.

Constitutive modeling, microstructure evolution, and processing map for a nitride-strengthened heat-resistant steel

A constitutive equation was established to describe the deformation behavior of a nitride-strengthened (NS) steel through isothermal compression simulation test. All the parameters in the constitutive equation including the constant and the activation energy were precisely calculated for the NS steel. The result also showed that from the stress-strain curves, there existed two different linear relationships between critical stress and critical strain in the NS steel due to the augmentation of auxiliary softening effect of the dynamic strain-induced transformation. In the calculation of processing maps, with the change of Zener-Hollomon value, three domains of different levels of workability were found, namely excellent workability region with equiaxed-grain microstructure, good workability region with “stripe” microstructure, and the poor workability region with martensitic-ferritic blend microstructure. With the increase of strain, the poor workability region first expanded, then shrank to barely existing, but appeared again at the strain of 0.6.

Antimicrobial efficacy of tobramycin polymeric nanoparticles for Pseudomonas aeruginosa infections in cystic fibrosis: formulation, characterisation and functionalisation with dornase alfa (DNase).

Inhaled antibiotics, such as tobramycin, for the treatment of Pseudomonas aeruginosa pulmonary infections are associated with the increase in life expectancy seen in cystic fibrosis (CF) patients over recent years. However, the effectiveness of this aminoglycoside is still limited by its inability to penetrate the thick DNA-rich mucus in the lungs of these patients, leading to low antibiotic exposure to resident bacteria. In this study, we created novel polymeric nanoparticle (NP) delivery vehicles for tobramycin. Using isothermal titration calorimetry, we showed that tobramycin binds with alginate polymer and, by exploiting this interaction, optimised the production of tobramycin alginate/chitosan NPs. It was established that NP antimicrobial activity against P. aeruginosa PA01 was equivalent to unencapsulated tobramycin (minimum inhibitory concentration 0.625 mg/L). Galleria mellonella was employed as an in vivo model for P. aeruginosa infection. Survival rates of 90% were observed following injection of NPs, inferring low NP toxicity. After infection with P. aeruginosa, we showed that a lethal inoculum was effectively cleared by tobramycin NPs in a dose dependent manner. Crucially, a treatment with NPs prior to infection provided a longer window of antibiotic protection, doubling survival rates from 40% with free tobramycin to 80% with NP treatment. Tobramycin NPs were then functionalised with dornase alfa (recombinant human deoxyribonuclease I, DNase), demonstrating DNA degradation and improved NP penetration of CF sputum. Following incubation with CF sputum, tobramycin NPs both with and without DNase functionalisation, exhibited anti-pseudomonal effects. Overall, this work demonstrates the production of effective antimicrobial NPs, which may have clinical utility as mucus-penetrating tobramycin delivery vehicles, combining two widely used CF therapeutics into a single NP formulation. This nano-antibiotic represents a strategy to overcome the mucus barrier, increase local drug concentrations, avoid systemic adverse effects and improve outcomes for pulmonary infections in CF.