The role of organoclay in promoting co-continuous morphology in high-density poly(ethylene)/poly(amide) 6 blends

The effect of organically modified clay on the morphology, rheology and mechanical properties of high-density polyethylene (HDPE) and polyamide 6 (PA6) blends (HDPE/PA6 = 75/25 parts) is studied. Virgin and filled blends were prepared by melt compounding the constituents using a twin-screw extruder. The influence of the organoclay on the morphology of the hybrid was deeply investigated by means of wide-angle X-ray diffractometry, transmission and scanning electron microscopies and quantitative extraction experiments. It has been found that the organoclay exclusively places inside the more hydrophilic polyamide phase during the melt compounding. The extrusion process promotes the formation of highly elongated and separated organoclay-rich PA6 domains. Despite its low volume fraction, the filled minor phase eventually merges once the extruded pellets are melted again, giving rise to a co-continuous microstructure. Remarkably, such a morphology persists for long time in the melt state. A possible compatibilizing action related to the organoclay has been investigated by comparing the morphology of the hybrid blend with that of a blend compatibilized using an ethylene–acrylic acid (EAA) copolymer as a compatibilizer precursor. The former remains phase separated, indicating that the filler does not promote the enhancement of the interfacial adhesion. The macroscopic properties of the hybrid blend were interpreted in the light of its morphology. The melt state dynamics of the materials were probed by means of linear viscoelastic measurements. Many peculiar rheological features of polymer-layered silicate nanocomposites based on single polymer matrix were detected for the hybrid blend. The results have been interpreted proposing the existence of two distinct populations of dynamical species: HDPE not interacting with the filler, and a slower species, constituted by the organoclay-rich polyamide phase, which slackened dynamics stabilize the morphology in the melt state. In the solid state, both the reinforcement effect of the filler and the co-continuous microstructure promote the enhancement of the tensile modulus. Our results demonstrate that adding nanoparticles to polymer blends allows tailoring the final properties of the hybrid, potentially leading to high-performance materials which combine the advantages of polymer blends and the merits of polymer nanocomposites.

Lyophilisation and sterilisation of liposomal vaccines to produce stable and sterile products

The advantages of liposomes as delivery systems for peptide, protein and DNA vaccines is well-recognised, unfortunately their application has been stinted by their instability during storage and their limited shelf-life. Further, sterilisation of these systems has been problematic, with degradation of the liposomes being reported after sterilisation using the various techniques available. Work form our laboratory has investigated techniques that can be applied to particulate liposomal vaccines such that they can be prepared in a freeze-dried and sterile format. In this article, we describe techniques for the lyophilisation, cryoprotection and sterilisation of liposomal vaccines. Applying these methods allows for the retention of both the chemical integrity of the lipids and the key physico-chemical characteristics of the liposomes (e.g., particle size, zeta potential, and dynamic viscosity), thus supporting the enhanced transition of liposomal vaccines from the bench to the clinic. © 2006 Elsevier Inc. All rights reserved.

Ophthalmic engineering:the development of novel instrumentation to further research in the field

The principle theme of this thesis is the advancement and expansion of ophthalmic research via the collaboration between professional Engineers and professional Optometrists. The aim has been to develop new and novel approaches and solutions to contemporary problems in the field. The work is sub divided into three areas of investigation; 1) High technology systems, 2) Modification of current systems to increase functionality, and 3) Development of smaller more portable and cost effective systems. High Technology Systems: A novel high speed Optical Coherence Tomography (OCT) system with integrated simultaneous high speed photography was developed achieving better operational speed than is currently available commercially. The mechanical design of the system featured a novel 8 axis alignment system. A full set of capture, analysis, and post processing software was developed providing custom analysis systems for ophthalmic OCT imaging, expanding the current capabilities of the technology. A large clinical trial was undertaken to test the dynamics of contact lens edge interaction with the cornea in-vivo. The interaction between lens edge design, lens base curvature, post insertion times and edge positions was investigated. A novel method for correction of optical distortion when assessing lens indentation was also demonstrated. Modification of Current Systems: A commercial autorefractor, the WAM-5500, was modified with the addition of extra hardware and a custom software and firmware solution to produce a system that was capable of measuring dynamic accommodative response to various stimuli in real time. A novel software package to control the data capture process was developed allowing real time monitoring of data by the practitioner, adding considerable functionality of the instrument further to the standard system. The device was used to assess the accommodative response differences between subjects who had worn UV blocking contact lens for 5 years, verses a control group that had not worn UV blocking lenses. While the standard static measurement of accommodation showed no differences between the two groups, it was determined that the UV blocking group did show better accommodative rise and fall times (faster), thus demonstrating the benefits of the modification of this commercially available instrumentation. Portable and Cost effective Systems: A new instrument was developed to expand the capability of the now defunct Keeler Tearscope. A device was developed that provided a similar capability in allowing observation of the reflected mires from the tear film surface, but with the added advantage of being able to record the observations. The device was tested comparatively with the tearscope and other tear film break-up techniques, demonstrating its potential. In Conclusion: This work has successfully demonstrated the advantages of interdisciplinary research between engineering and ophthalmic research has provided new and novel instrumented solutions as well as having added to the sum of scientific understanding in the ophthalmic field.

The development and investigation of a novel pulsatile heart assist device

Cardiovascular diseases (CVD) contributed to almost 30% of worldwide mortality; with heart failure being one class of CVD. One popular and widely available treatment for heart failure is the intra-aortic balloon pump (IABP). This heart assist device is used in counterpulsation to improve myocardial function by increasing coronary perfusion, and decreasing aortic end-diastolic pressure (i.e. the resistance to blood ejection from the heart). However, this device can only be used acutely, and patients are bedridden. The subject of this research is a novel heart assist treatment called the Chronic Intermittent Mechanical Support (CIMS) which was conceived to offer advantages of the IABP device chronically, whilst overcoming its disadvantages. The CIMS device comprises an implantable balloon pump, a percutaneous drive line, and a wearable driver console. The research here aims to determine the haemodynamic effect of balloon pump activation under in vitro conditions. A human mock circulatory loop (MCL) with systemic and coronary perfusion was constructed, capable of simulating various degrees of heart failure. Two prototypes of the CIMS balloon pump were made with varying stiffness. Several experimental factors (balloon inflation/deflation timing, Helium gas volume, arterial compliance, balloon pump stiffness and heart valve type) form the factorial design experiments. A simple modification to the MCL allowed flow visualisation experiments using video recording. Suitable statistical tests were used to analyse the data obtained from all experiments. Balloon inflation and deflation in the ascending aorta of the MCL yielded favourable results. The sudden balloon deflation caused the heart valve to open earlier, thus causing longer valve opening duration in a cardiac cycle. It was also found that pressure augmentation in diastole was significantly correlated with increased cardiac output and coronary flowrate. With an optimum combination (low arterial compliance and low balloon pump stiffness), systemic and coronary perfusions were increased by 18% and 21% respectively, while the aortic end-diastolic pressure (forward flow resistance) decreased by 17%. Consequently, the ratio of oxygen supply and demand to myocardium (endocardial viability ratio, EVR) increased between 33% and 75%. The increase was mostly attributed to diastolic augmentation rather than systolic unloading.

A decade of silicone hydrogel development:surface properties, mechanical properties, and ocular compatibility

Since the initial launch of silicone hydrogel lenses, there has been a considerable broadening in the range of available commercial material properties. The very mobile silicon–oxygen bonds convey distinctive surface and mechanical properties on silicone hydrogels, in which advantages of enhanced oxygen permeability, reduced protein deposition, and modest frictional interaction are balanced by increased lipid and elastic response. There are now some 15 silicone hydrogel material variants available to practitioners; arguably, the changes that have taken place have been strongly influenced by feedback based on clinical experience. Water content is one of the most influential properties, and the decade has seen a progressive rise from lotrafilcon-A (24%) to efrofilcon-A (74%). Moduli have decreased over the same period from 1.4 to 0.3 MPa, but not solely as a result of changes in water content. Surface properties do not correlate directly with water content, and ingenious approaches have been used to achieve desirable improvements (e.g., greater lubricity and lower contact angle hysteresis). This is demonstrated by comparing the hysteresis value of the earliest (lotrafilcon-A, >40°) and most recent (delefilcon-A, <10°) coated silicone hydrogels. Although wettability is important, it is not of itself a good predictor of ocular response because this involves a much wider range of physicochemical and biochemical factors. The interference of the lens with ocular dynamics is complex leading separately to tissue–material interactions involving anterior and posterior lens surfaces. The biochemical consequences of these interactions may hold the key to a greater understanding of ocular incompatibility and end of day discomfort.

Evaluation of modern intraocular lenses

Accommodating Intraocular Lenses (IOLs), multifocal IOLs (MIOLs) and toric IOLs are designed to provide a greater level of spectacle independency post cataract surgery. All of these IOLs are reliant on the accurate calculation of intraocular lens power determined through reliable ocular biometry. A standardised defocus area metric and reading performance index metric were devised for the evaluation of the range of focus and the reading ability of subjects implanted with presbyopic correcting IOLs. The range of clear vision after implantation of an MIOL is extended by a second focal point; however, this results in the prevalence of dysphotopsia. A bespoke halometer was designed and validated to assess this photopic phenomenon. There is a lack of standardisation in the methods used for determining IOL orientation and thus rotation. A repeatable, objective method was developed to allow the accurate assessment of IOL rotation, which was used to determine the rotational and positional stability of a closed loop haptic IOL. A new commercially available biometry device was validated for use with subjects prior to cataract surgery. The optical low coherence reflectometry instrument proved to be a valid method for assessing ocular biometry and covered a wider range of ocular parameters in comparison with previous instruments. The advantages of MIOLs were shown to include an extended range of clear vision translating into greater reading ability. However, an increased prevalence of dysphotopsia was shown with a bespoke halometer, which was dependent on the MIOL optic design. Implantation of a single optic accommodating IOL did not improve reading ability but achieved high subjective ratings of near vision. The closed-loop haptic IOL displayed excellent rotational stability in the late period but relatively poor rotational stability in the early period post implantation. The orientation error was compounded by the high frequency of positional misalignment leading to an extensive overall misalignment of the IOL. This thesis demonstrates the functionality of new IOL lens designs and the importance of standardised testing methods, thus providing a greater understanding of the consequences of implanting these IOLs. Consequently, the findings of the thesis will influence future designs of IOLs and testing methods.

Networking - a statistical physics perspective

Networking encompasses a variety of tasks related to the communication of information on networks; it has a substantial economic and societal impact on a broad range of areas including transportation systems, wired and wireless communications and a range of Internet applications. As transportation and communication networks become increasingly more complex, the ever increasing demand for congestion control, higher traffic capacity, quality of service, robustness and reduced energy consumption requires new tools and methods to meet these conflicting requirements. The new methodology should serve for gaining better understanding of the properties of networking systems at the macroscopic level, as well as for the development of new principled optimization and management algorithms at the microscopic level. Methods of statistical physics seem best placed to provide new approaches as they have been developed specifically to deal with nonlinear large-scale systems. This review aims at presenting an overview of tools and methods that have been developed within the statistical physics community and that can be readily applied to address the emerging problems in networking. These include diffusion processes, methods from disordered systems and polymer physics, probabilistic inference, which have direct relevance to network routing, file and frequency distribution, the exploration of network structures and vulnerability, and various other practical networking applications. © 2013 IOP Publishing Ltd.

Effects of rare-earth co-doping on the local structure of rare-earth phosphate glasses using high and low energy X-ray diffraction

Rare-earth co-doping in inorganic materials has a long-held tradition of facilitating highly desirable optoelectronic properties for their application to the laser industry. This study concentrates specifically on rare-earth phosphate glasses, (R2O3)x(R'2O3)y(P2O5)1-(x+y), where (R, R') denotes (Ce, Er) or (La, Nd) co-doping and the total rare-earth composition corresponds to a range between metaphosphate, RP3O9, and ultraphosphate, RP5O14. Thereupon, the effects of rare-earth co-doping on the local structure are assessed at the atomic level. Pair-distribution function analysis of high-energy X-ray diffraction data (Qmax = 28 Å-1) is employed to make this assessment. Results reveal a stark structural invariance to rare-earth co-doping which bears testament to the open-framework and rigid nature of these glasses. A range of desirable attributes of these glasses unfold from this finding; in particular, a structural simplicity that will enable facile molecular engineering of rare-earth phosphate glasses with 'dial-up' lasing properties. When considered together with other factors, this finding also demonstrates additional prospects for these co-doped rare-earth phosphate glasses in nuclear waste storage applications. This study also reveals, for the first time, the ability to distinguish between P-O and PO bonding in these rare-earth phosphate glasses from X-ray diffraction data in a fully quantitative manner. Complementary analysis of high-energy X-ray diffraction data on single rare-earth phosphate glasses of similar rare-earth composition to the co-doped materials is also presented in this context. In a technical sense, all high-energy X-ray diffraction data on these glasses are compared with analogous low-energy diffraction data; their salient differences reveal distinct advantages of high-energy X-ray diffraction data for the study of amorphous materials. © 2013 The Owner Societies.

The usability of semantic search tools:a review

The goal of semantic search is to improve on traditional search methods by exploiting the semantic metadata. In this paper, we argue that supporting iterative and exploratory search modes is important to the usability of all search systems. We also identify the types of semantic queries the users need to make, the issues concerning the search environment and the problems that are intrinsic to semantic search in particular. We then review the four modes of user interaction in existing semantic search systems, namely keyword-based, form-based, view-based and natural language-based systems. Future development should focus on multimodal search systems, which exploit the advantages of more than one mode of interaction, and on developing the search systems that can search heterogeneous semantic metadata on the open semantic Web.

The synthesis and properties of some hydrazines

A new synthetic method, applicable to the preparation of a wide range of hydrazine derivatives, is described. This involves the diborane reduction of a hydrazone, or, more conveniently, the reductive-condensation of a hydrazine and the appropriate aldehyde (or ketone). The method gives high yields and provides a particularly simple route to the relatively inaccessible 1,2-disubstituted hydrazines bearing a different group on each nitrogen. The new method has also been applied to the preparation of 1,2-disubstituted hydrazines with the same group on both nitrogens (via the azine), the very rare 1 ,2-disubstituted hydrazines bearing a tert-butyl group, trisubstituted hydrazines and monosubstituted hydrazines. Application of the reaction to the preparation of diaziridines has also been investigated. A mechanism for the reduction, supported by the isolation of a boron-containing intermediate, is suggested. Some limitations of the procedure are discussed. A general i.r. method of distinguishing the isomeric disubstituted hydrazines, as stable salts, has been developed. This has the advantages of speed and simplicity over previous methods. The mass spectra of a series of monosubstituted hydrazines, a series of 1,2-disubstituted hydrazines and some 1-benzoyl 2-alkylhydrazines have been examined in detail. The spectra are generally dominated byα -cleavage processes and the compounds show a variety of interesting rearrangement reactions. The mass spectra of some 1, 1-disubstituted hydrazines and some trisubstituted hydrazines have also been examined. Rearrangement processes occurring in the mass spectrum of tropylium fluoroborate have been examined. Similar rearrangements have been found in the spectrum of trityl fluoroborate and may be of general occurrence in the mass spectra of aromatic fluoroborates. Chemical shift values for some groups on hydrazine nitrogen are recorded and the results of tumour inhibitory tests on some hydrazines are also given.

Implementation and characterization of liquid-level sensor based on a long-period fiber grating Mach-Zehnder interferometer

An optical liquid-level sensor (LLS) based on a long-period fiber grating (LPG) interferometer is proposed and experimentally demonstrated. Two identical 3-dB LPGs are fabricated to form an in-fiber Mach-Zehnder interferometer, and the fiber portion between two LPGs is exposed to the liquid as the sensing element. The sensitivity and measurement range of the sensors employing different orders of cladding modes are investigated both theoretically and experimentally. The experimental results show good linearity and large measurement range. One of the significant advantages of such a sensing structure is that the measurement level is not limited to the length of the LPG itself. Also, the measurement range and sensitivity of the proposed LLS can be readily tailored for a particular applications.

A simple bioanalytical method for the quantification of antiepileptic drugs in dried blood spots

An increasing number of publications on the dried blood spot (DBS) sampling approach for the quantification of drugs and metabolites have been spurred on by the inherent advantages of this sampling technique. In the present research, a selective and sensitive high-performance liquid chromatography method for the concurrent determination of multiple antiepileptic drugs (AEDs) [levetiracetam (LVT), lamotrigine (LTG), phenobarbital (PHB)], carbamazepine (CBZ) and its active metabolite carbamazepine-10,11 epoxide (CBZE)] in a single DBS has been developed and validated. Whole blood was spotted onto Guthrie cards and dried. Using a standard punch (6 mm diameter), a circular disc was punched from the card and extracted with methanol: acetonitrile (3:1, v/v) containing hexobarbital (Internal Standard) and sonicated prior to evaporation. The extract was then dissolved in water and vortex mixed before undergoing solid phase extraction using HLB cartridges. Chromatographic separation of the AEDs was achieved using Waters XBridge™ C18 column with a gradient system. The developed method was linear over the concentration ranges studied with r ≥ 0.995 for all compounds. The lower limits of quantification (LLOQs) were 2, 1, 2, 0.5 and 1 μg/mL for LVT, LTG, PHB, CBZE and CBZ, respectively. Accuracy (%RE) and precision (%CV) values for within and between day were <20% at the LLOQs and <15% at all other concentrations tested. This method was successfully applied to the analysis of the AEDs in DBS samples taken from children with epilepsy for the assessment of their adherence to prescribed treatments.

VaxiJen:a server for prediction of protective antigens, tumour antigens and subunit vaccines

Background - Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results - Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion - VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods.

Evaluation of Impact of Beam Size on Fibre Bragg Grating Fabrication

Fabrication of gratings has gone a long way since the onset by Kenneth Hill in 1976. Basic fabrication techniques such as holographic and phase-mask which have distinguishing advantages (variable wavelength, and high repeatability consecutively) have since been modified in an effort to combine the advantages of both methods. These basic methods are inherently simple and have few controls, they have been combined and modified over time to enable the possibility of fabricating gratings with complex modulation index and phase profiles.

Evaluation of impact of beam size on fibre Bragg grating fabrication

Fabrication of gratings has gone a long way since the onset by Kenneth Hill in 1976. Basic fabrication techniques such as holographic and phase-mask which have distinguishing advantages (variable wavelength, and high repeatability consecutively) have since been modified in an effort to combine the advantages of both methods. These basic methods are inherently simple and have few controls, they have been combined and modified over time to enable the possibility of fabricating gratings with complex modulation index and phase profiles.