Development of a polymer theranostic for prostate cancer

Theranostics offers an improved treatment strategy for prostate cancer by facilitating simultaneous targeting of tumour cells with subsequent drug delivery and imaging. In this report we describe the synthesis of hyperbranched polymers that are biocompatible, can specifically target and be internalised by prostate cancer cells (through targeting of prostate-specific membrane antigen – PSMA) and ultimately facilitate controlled delivery of a model drug. The theranostic also incorporates a far-red fluorescent dye that allows tracking of the polymer via optical imaging. Controlled synthesis of the polymer is achieved via reversible addition fragmentation chain transfer polymerisation of polyethylene glycol monomethyl methacrylate, with ethylene glycol dimethacrylate as the branching agent. Incorporation of 20 mol% of an hydrazide-methacrylate monomer allows post-ligation of a model drug, fluorene-2-carboxaldehyde, through a hydrolytically-degradable hydrazone linkage. The rate of degradation of this particular linker was enhanced at endosomal pH (pH = 5.5) where [similar]95% of the model drug was released in 4 hours compared to less than 5% released over the same period at physiological pH. The theranostic showed high uptake into prostate cancer cells expressing prostate-specific membrane antigen, while minimal uptake was observed in PC3 cells negative for PSMA, highlighting the enhanced efficacy of the targeting ligand.

Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

Computation of Mathematical Models for Complex Industrial Processes

Designed for undergraduate and postgraduate students, academic researchers and industrial practitioners, this book provides comprehensive case studies on numerical computing of industrial processes and step-by-step procedures for conducting industrial computing. It assumes minimal knowledge in numerical computing and computer programming, making it easy to read, understand and follow. Topics discussed include fundamentals of industrial computing, finite difference methods, the Wavelet-Collocation Method, the Wavelet-Galerkin Method, High Resolution Methods, and comparative studies of various methods. These are discussed using examples of carefully selected models from real processes of industrial significance. The step-by-step procedures in all these case studies can be easily applied to other industrial processes without a need for major changes and thus provide readers with useful frameworks for the applications of engineering computing in fundamental research problems and practical development scenarios.

Durability performance of carbon fibre-reinforced polymer strengthened circular hollow steel members under cold weather

The use of circular hollow steel members has attracted a great deal of attention during past few years because of having excellent structural properties, aesthetic appearance, corrosion and fire protection capability. However, no one can deny the structural deficiency of such structures due to reduction of strength when they are exposed to severe environmental conditions such as marine environment, cold and hot weather. Hence strengthening and retrofitting of structural steel members is now very imperative. This paper presents the findings of a research program that was conducted to study the bond durability of carbon fibre-reinforced polymer (CFRP) strengthened steel tubular members under cold weather and tested under four-point bending. Six number of CFRP-strengthened specimens and one unstrengthened specimen were considered in this program. The three specimens having sand blasted surface to be strengthened was pre-treated with MBrace primer and other three were remained untreated and then cured under ambient temperature at least four weeks and cold weather (3 C) for three and six months period of time. Quasi-static tests were then performed on beams to failure under four-point bending. The structural response of each specimen was predicted in terms of failure load, mid-span deflection, composite beam behaviour and failure mode. The research outcomes show that the cold weather immersion had an adverse effect on durability of CFRP-strengthened steel structures. Moreover, the epoxy based adhesion promoter was found to enhance the bond durability in plastic range. The analytical models presented in this study were found to be in good agreement in terms of predicting ultimate load and deflection. Finally, design factors are proposed to address the short-terms durability performance under cold weather.

Synonymization of key pest species within the Bactrocera dorsalis species complex (Diptera: Tephritidae): Taxonomic changes based on a review of 20 years of integrative morphological, molecular, cytogenetic, behavioural and chemoecological data

Bactrocera papayae Drew & Hancock, Bactrocera philippinensis Drew & Hancock, Bactrocera carambolae Drew & Hancock, and Bactrocera invadens Drew, Tsuruta & White are four horticultural pest tephritid fruit fly species that are highly similar, morphologically and genetically, to the destructive pest, the Oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). This similarity has rendered the discovery of reliable diagnostic characters problematic, which, in view of the economic importance of these taxa and the international trade implications, has resulted in ongoing difficulties for many areas of plant protection and food security. Consequently, a major international collaborative and integrated multidisciplinary research effort was initiated in 2009 to build upon existing literature with the specific aim of resolving biological species limits among B. papayae, B. philippinensis, B. carambolae, B. invadens and B. dorsalis to overcome constraints to pest management and international trade. Bactrocera philippinensis has recently been synonymized with B. papayae as a result of this initiative and this review corroborates that finding; however, the other names remain in use. While consistent characters have been found to reliably distinguish B. carambolae from B. dorsalis, B. invadens and B. papayae, no such characters have been found to differentiate the latter three putative species. We conclude that B. carambolae is a valid species and that the remaining taxa, B. dorsalis, B. invadens and B. papayae, represent the same species. Thus, we consider B. dorsalis (Hendel) as the senior synonym of B. papayae Drew and Hancock syn.n. and B. invadens Drew, Tsuruta & White syn.n. A redescription of B. dorsalis is provided. Given the agricultural importance of B. dorsalis, this taxonomic decision will have significant global plant biosecurity implications, affecting pest management, quarantine, international trade, postharvest treatment and basic research. Throughout the paper, we emphasize the value of independent and multidisciplinary tools in delimiting species, particularly in complicated cases involving morphologically cryptic taxa.

Design of high mobility DPP-based polymer semiconductors for organic thin film transistors

π-Conjugated polymers are the most promising semiconductor materials to enable printed organic thin film transistors (OTFTs) due to their excellent solution processability and mechanical robustness. However, solution-processed polymer semiconductors have shown poor charge transport properties mainly originated from the disordered polymer chain packing in the solid state as compared to the thermally evaporated small molecular organic semiconductors. The low charge carrier mobility, typically < 0.1 cm2 /V.s, of polymer semiconductors poses a challenge for most intended applications such as displays and radio-frequency identification (RFID) tags. Here we present our recent results on the dike topyrrolopyrrole (DPP)-based polymers and demonstrate that when DPP is combined with appropriate electron donating moieties such as thiophene and thienothiophene, very high charge carrier mobility values of ~1 cm2/V.s could be achieved.

Density of trap states in a polymer field-effect transistor

We report a more accurate method to determine the density of trap states in a polymer field-effect transistor. In the approach, we describe in this letter, we take into consideration the sub-threshold behavior in the calculation of the density of trap states. This is very important since the sub-threshold regime of operation extends to fairly large gate voltages in these disordered semiconductor based transistors. We employ the sub-threshold drift-limited mobility model (for sub-threshold response) and the conventional linear mobility model for above threshold response. The combined use of these two models allows us to extract the density of states from charge transport data much more accurately. We demonstrate our approach by analyzing data from diketopyrrolopyrrole based co-polymer transistors with high mobility. This approach will also work well for other disordered semiconductors in which sub-threshold conduction is important.

Enhanced interfacial thermal transport across graphene–polymer interfaces by grafting polymer chains

Thermal transport in graphene-polymer nanocomposite is complicated and has not been well understood. The interfacial thermal transport between graphene nanofiller and polymer matrix is expected to play a key role in controlling the overall thermal performance of graphene-polymer nanocomposite. In this work, we investigated the thermal transport across graphene-polymer interfaces functionalized with end-grafted polymer chains using molecular dynamics simulations. The effects of grafting density, chain length and initial morphology on the interfacial thermal transport were systematically investigated. It was found that end-grafted polymer chains could significantly enhance interfacial thermal transport and the underlying mechanism was considered to be the enhanced vibration coupling between graphene and polymer. In addition, a theoretical model based on effective medium theory was established to predict the thermal conductivity in graphene-polymer nanocomposites.

Investigating tween children's capacity to conceptualise the complex issue of wellbeing

Wellbeing is an area that has gained increased global focus, particularly when considering children’s lives. With the growing focus on children’s wellbeing, it is apparent that this is an important aspect that is being considered in the policy and provision designed for children. The decision-making surrounding wellbeing provision for children typically occurs without the direct input of the children that these services are designed to benefit. With the children’s capacities being variably considered in wider society, opportunities for children to participate in decision-making on matters that affect them are often limited. The absence of children’s perspectives on matters that affect their lives, such as wellbeing, reveal that adults may be missing a key perspective when seeking to understand and cater for children’s wellbeing needs. This article outlines the results of a study that investigated how children aged 8 to 12 years o age (tweens) defined and conceptualised wellbeing. This article proposes that children can be included in the conceptualisation and development of policy and provision designed to benefit them and argues for increased presence of the voice and participation of children in wider societal initiatives.

Assessment of the effects of CT dose in averaged x-ray CT images of a dose-sensitive polymer gel

The signal-to-noise ratio achievable in x-ray computed tomography (CT) images of polymer gels can be increased by averaging over multiple scans of each sample. However, repeated scanning delivers a small additional dose to the gel which may compromise the accuracy of the dose measurement. In this study, a NIPAM-based polymer gel was irradiated and then CT scanned 25 times, with the resulting data used to derive an averaged image and a "zero-scan" image of the gel. Comparison between these two results and the first scan of the gel showed that the averaged and zero-scan images provided better contrast, higher contrast-to- noise and higher signal-to-noise than the initial scan. The pixel values (Hounsfield units, HU) in the averaged image were not noticeably elevated, compared to the zero-scan result and the gradients used in the linear extrapolation of the zero-scan images were small and symmetrically distributed around zero. These results indicate that the averaged image was not artificially lightened by the small, additional dose delivered during CT scanning. This work demonstrates the broader usefulness of the zero-scan method as a means to verify the dosimetric accuracy of gel images derived from averaged x-ray CT data.

Finite element modeling of carbon fibre reinforced polymer (CFRP) strengthened steel tubes under axial impact

Steel hollow sections used in structures such as bridges, buildings and space structures involve different strengthening techniques according to their structural purpose and shape of the structural member. One such technique is external bonding of CFRP sheets to steel tubes. The performance of CFRP strengthening for steel structures has been proven under static loading while limited studies have been conducted on their behaviour under impact loading. In this study, a comprehensive numerical investigation is carried out to evaluate the response of CFRP strengthened steel tubes under dynamic axial impact loading. Impact force, axial deformation impact velocities are studied. The results of the numerical investigations are validated by experimental results. Based on the developed finite element (FE) model several output parameters are discussed. The results show that CFRP wrapping is an effective strengthening technique to increase the axial dynamic load bearing capacity by increasing the stiffness of the steel tube.