The role of telomerase and hTERT in the human tear film and ocular surface

Telomerase is an enzyme that reverses the attrition of the chromosomal ends. It consists of ribonucleic acid (RNA) and a catalytic unit known as human reverse transcriptase (hTERT). Telomerase activity has been shown to increase the cellular life span, while hTERT activity without the RNA decreases cellular oxidation and enhances nerve regeneration. Telomerase/hTERT has been explored extensively in the body’s tissues and fluids and has not been explored in the tear film and ocular surface. The tear film can reflect the status of the ocular surface and is easily accessible for collection and analysis. It is, therefore, of interest to investigate the role of telomerase/hTERT in the tear film in both health and disease. This thesis aimed to investigate the role of telomerase/hTERT in the healthy tear film, as well as in the presence of inflammation and neuronal changes. The project included the following studies: method development in protein analysis, telomerase activity, and corneal dendritic cell density; hTERT detection and telomerase activity in the tear film; the variation of hTERT in healthy individuals during the sleep/wake cycle; the variation of hTERT in neophyte contact lens wearers during the sleep/wake cycle; hTERT in mild inflammation in patients with dry eye disease; and hTERT in diabetic peripheral neuropathy. The assessment of hTERT, in relationship to inflammation, was accompanied by monitoring inflammatory biomarkers, including interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in the tear film, as well as dendritic cells in the cornea. Relationships with neuronal activity on the ocular surface were explored by parallel observation of corneal nerve distribution. hTERT detection in healthy tear film was confirmed by western blotting, while telomerase activity was undetected, using real-time polymerase chain reaction. During the day, hTERT behaviour in healthy individuals remained constant and upregulated during sleep. This was accompanied by increased activity of corneal dendritic cells. Contact lens wear induced a slight increase in hTERT levels but did not otherwise alter the sleep/wake cycle. In dry eye disease, hTERT levels were higher compared to the healthy controls, accompanied by a low level of changes in cornea nerves. In diabetes, hTERT was upregulated only in those with severe peripheral neuropathy compared to mild peripheral neuropathy. These changes corresponded with disease-related alteration of the corneal neural plexus. In addition, there was a reduction in hTERT levels in females compared to males. In conclusion, telomerase activity in the healthy tear film is undetectable, while hTERT appears to be a valuable biomarker to evaluate the inflammatory status of the ocular surface and might reflect the condition of corneal nerve parameters. Further study of hTERT activity in the tear film is warranted

Nonlinear predictive restricted structure control

This thesis defines new developments in predictive restricted structure control for industrial applications. It begins by describing the augmented system for both state-space and polynomial model descriptions. These descriptions can contain the plant model, the disturbance model, and any additional essential model subsystems. It then describes the predictive restricted structure control solution for both linear and nonlinear systems in state-space form. The solution utilizes the recent development in nonlinear predictive generalized minimum variance by adding a general operator subsystem that defines nonlinear system along with the linear or the linear parameter varying output subsystem. The next contribution is the polynomial predictive restricted structure control algorithm for polynomial linear parameter varying model that may result from nonlinear equations or experimental data-driven model identification. This algorithm utilizes the generalised predictive control method to approximate and control nonlinear systems in the linear parameter varying system inputoutput transfer operator matrices. The solution is simple in unconstrained and constrained optimization solutions and required a small computing capacity. Four examples have been chosen to test the algorithms for different nonlinear characteristics. In the first three examples, state-space versions of the algorithm for the linear, the quasi-linear parameter varying and the state-dependent were employed to control the quadruple tank process, electronic throttle body, and the continuous stirred tank reactors. In the last example, the polynomial linear parameter varying restricted structure controller is used to control automotive variable camshaft timing system.This thesis defines new developments in predictive restricted structure control for industrial applications. It begins by describing the augmented system for both state-space and polynomial model descriptions. These descriptions can contain the plant model, the disturbance model, and any additional essential model subsystems. It then describes the predictive restricted structure control solution for both linear and nonlinear systems in state-space form. The solution utilizes the recent development in nonlinear predictive generalized minimum variance by adding a general operator subsystem that defines nonlinear system along with the linear or the linear parameter varying output subsystem. The next contribution is the polynomial predictive restricted structure control algorithm for polynomial linear parameter varying model that may result from nonlinear equations or experimental data-driven model identification. This algorithm utilizes the generalised predictive control method to approximate and control nonlinear systems in the linear parameter varying system inputoutput transfer operator matrices. The solution is simple in unconstrained and constrained optimization solutions and required a small computing capacity. Four examples have been chosen to test the algorithms for different nonlinear characteristics. In the first three examples, state-space versions of the algorithm for the linear, the quasi-linear parameter varying and the state-dependent were employed to control the quadruple tank process, electronic throttle body, and the continuous stirred tank reactors. In the last example, the polynomial linear parameter varying restricted structure controller is used to control automotive variable camshaft timing system

Folded waveguide resonator filter for communication and radar systems

In this thesis, a primary investigation into developing a compact and low-loss bandpass filter, using novel folded waveguide resonators with a footprint reduction, has been addressed. A slot coupling between adjacent resonators is introduced, which is characterized by using full-wave EM simulations and verified experimentally. Two designs of 2-pole folded waveguide resonator filters of this type have been considered, fabricated and tested. In this thesis, an even more compact FWG resonator filter using a novel slot technique is reported. The attainable size reduction is about 50%, and the filter design is based on theoretical and full-wave electromagnetic (EM) simulations. Based on FWG structure, two types of folded waveguide resonators have been studied and considered the half-wavelength resonator and the quarter-wavelength resonator. Moreover, both structures for the realization of microwave cavities with high-Q, with the result of a high spurious free range and reduced footprint, have been evaluated. Furthermore, a novel folded waveguide resonator with about a 75 % reduction of the volume from the conventional size has been described. For comparison, two types of folded waveguide resonators have been studied, i.e. the quarter-wavelength resonator of square shape and the newly proposed triangular shape. In addition, a demonstration of a filter application for miniature triangular folded waveguide resonators has been designed and simulated using an EM simulator. In addition, numbers of experiments have been conducted to develop cavity FWG and Substrate Integrated folded waveguide SIFW resonator filters using a folded structure, which is the main aim of this thesis. Furthermore, this thesis deals with the simulation and implementation for many designs and topologies of FWG and SIFW resonator filters and their frequency response. Simulation and experimental results were presented to validate the design and to show the advantages of these types of filters. In addition, a new type of filter with a compact multi-layer structure and low loss is attractive for implementation with advanced device technologies, such as micromachining, LTCC and LCP technologies

Vacuum insulated panels for sustainable buildings: a review of research and applications

New research has identified vacuum insulation panels (VIPs) as highly efficient insulators for use in building construction. They are reported to be several times more effective than conventional materials of a similar thickness in terms of thermal conductivity. Because of their smaller space requirement, VIPs maximize the internal usage area of buildings and so reduce the cost of construction. There are however some obstacles that have hindered the application of VIPs, notably their high cost, susceptibility to perforation and the long-term water and gas effects that worsen their performance. This paper reviews the contemporary research on VIP as a state-of-the-art material for building insulation. The main components and physical principles of VIP performance are discussed. Finally, the review of VIPs available on the market and their performance is provided

User acceptance of m-government services in Saudi Arabia : an SEM approach

In spite of many benefits normally attributed to the use of e-government and its more recent variety mobile- (m-) government, there are still many obstacles reported facing the adoption of both, especially in developing countries. We explore the situation in one of them, namely Saudi Arabia, aiming to study factors affecting citizens' adoption of m-government. We tailor a new conceptual model for m-government adoption by citizens based on Technology Acceptance Model (TAM) and specifically consider important factors such as perceived service quality, perceived trust, user satisfaction and perceived mobility. We also tailor measuring those factors to account for the specifics of the new mobile aspect in the existing theories and carry out a large scale survey (695 analysed respondents from King Saud University and Immam Muhammed Bin Saud University) followed by quantitative analysis involving structural equation modelling. Our results support most of the anticipated relationships between the factors and adoption, and will help policy makers and developers of e-government systems to increase citizen's adoption

Developing and validating an instrument for measuring mobile government adoption in Saudi Arabia

Many governments recently started to change the ways of providing their services by allowing their citizens to access services from anywhere without the need of visiting the location of the service provider. Mobile government (M-government) is one of the techniques that fulfill that goal. It has been adopted by many governments. M-government can be defined as an implementation of Electronic Government (E-Government) by using mobile technology with the aim of improving service delivery to citizens, businesses and all government agencies. There have been several research projects developing models to understand the behavior of individuals towards the adoption of m-government. This paper proposes a model for adoption of m-government services in Saudi Arabia by extending Technology Acceptance Model (TAM) by introducing external factors. This paper also reports on the development of a survey instrument designed to measure user perception of mobile government acceptance. A survey instrument has been developed by using existing scales from prior instruments and a pilot study has been conducted by distributing the survey to 33 participants. As a result, a survey instrument has been refined to retain 43 items. The results also showed that the reliabilities of all the scales in the survey instrument are above the levels acceptable in current academic research, thus the instruments developed by us are capable of analyzing the factors in M-government adoption

Using focus group method to identifying citizen requirements to Saudi mobile government services

Mobile government services implementation faces several challenges in developing countries. This paper studies some of those challenges in the context of Saudi Arabia. The study aims to investigate factors affecting m-government acceptance in Saudi Arabia, including ease of use, usefulness, service quality, trust, intention to use and users' satisfaction. Our investigation will help in integrating the m-government services in citizens' everyday life. We collected and analyzed our data from focus groups. These focus groups are from King Saud University and Imam Muhammed Bin Saud University, so the samples size are five and seven participants, respectively. We found that there are some factors to identifying citizen requirements to Saudi mobile government services. These services should be easy to use and not require too much effort. Also, these services must be fully trusted

The effect of the HLA B27 allele on the immune response to acute HCV in HIV infected patients

In mono-infected individuals, the HLA-B27 allele is strongly associated with spontaneous clearance of HCV in association with a strong CD8+ response targeted against a single epitope within the HCV RNA-dependent RNA polymerase (NS5B). We studied variation across the whole HCV genome and T cell responses over time in a rare cohort of HLA-B27+ patients with acute HCV and HIV co-infection, the majority of whom progressed to chronicity. We used next generation sequencing to detect changes within and outwith the immuno-dominant HLA-B27 restricted HCV-specific CD8+ T cell epitope NS5B2841-2849 (ARMILMTHF) during evolving progression of early HCV infection. Within the Acute HCV UK cohort, 10 patients carried the HLA B27 allele. Of these, 3/8 patients (37.5%) with HIV infection and 2/2 (100%) without HIV spontaneously cleared HCV (p=0.44). Sequential samples from nine HLA-B27+ patients (2 with monoinfection and 7 with HIV co-infection) were available for analysis (four spontaneous clearers and five evolving progressors). Mutations identified using NGS were assessed using a replicon genotype 1a system to evaluate viral fitness. Multiple mutations within the HLA-B27 restricted NS5B2841-2849 epitope were associated with progression to chroncity whereas patients who cleared the HCV infection spontaneously had no or only one mutation at this site (p=0.03). A triple NS5B2841-2849 mutant observed during progression to chronicity was associated with restored replication when compared to wild-type virus while single or double mutants were significantly associated with impaired replication (p=0.0495). T cell responses measured in these patients using ELISpot and flow cytometry. HLA-B27+ patients had significantly higher IFN-γ responses than patients who were HLA-B27- (p=0.0014). Those who progressed to chronicity had lower IFN-γ responses than those who cleared HCV (p=0.0011). Mono-infected patients had higher IFN-γ responses compared to co-infected patients (p=0.0015). HIV co-infection is associated with a lower likelihood of spontaneous clearance of HCV in HLA B27+ patients and this is associated with impaired T cell function in this group

A new approach for two-terminal electronic memory devices - Storing information on silicon nanowires

open access articleThe work described in this paper focuses on the utilisation of silicon nanowires as the information storage element in flash-type memory devices. Silicon nanostructures have attracted attention due to interesting electrical and optical properties, and their potential integration into electronic devices. A detailed investigation of the suitability of silicon nanowires as the charge storage medium in two-terminal non-volatile memory devices are presented in this report. The deposition of the silicon nanostructures was carried out at low temperatures (less than 400 °C) using a previously developed a novel method within our research group. Two-terminal non-volatile (2TNV) memory devices and metal-insulator-semiconductor (MIS) structures containing the silicon nanowires were fabricated and an in-depth study of their characteristics was carried out using current-voltage and capacitancetechniques

Levels of evidence within cardiovascular medicine research in Saudi Arabia: a systematic review

International commitments to reduce the prevalence of non-communicable disease have led the Government of Saudi Arabia to invest more in research related to cardiovascular disease. However, the strength of evidence derived from these research activities remains unclear. The aim of our study was to examine the level of evidence within clinical Cardiovascular Medicine research in Saudi Arabia. We conducted a systematic review of published articles that included a population from Saudi Arabia. Electronic databases EMBASE and MEDLINE (Ovid) were searched up to 25th of April 2021, supplemented by a second search in CENTRAL (Cochrane Central Register of Controlled Trials) and www. clinicaltrials.gov. In addition, the Snowball-and Pearl-growing methods of search were conducted for finding addi-tional eligible articles. Finally, a search was conducted in PubMed database for all eligible articles published by Journal of the Saudi Heart Association from the first indexed issue up to April 2021. Level of evidence of reviewed articles was determined using the Oxford Level of Evidence 2 scale. We calculated the mean level of evidence over 5-year periods, and explored evidence for a time trend for number of published articles and LOE using linear regression. Of the 1113 records identified, 418 met the inclusion criteria for analysis. The articles were published between September 1986 and March 2021. More than half of the included articles were level IV studies (n = 242, 57.8%). Furthermore, we observed no trend over the years for increased mean of level of evidence (β =-0.07, 95% CI [-0.20,-0.06], p = 0.236). Overall, the level of evidence produced by the articles in clinical Cardiovascular Medicine in Saudi Arabia is very low. Prioritizing higher-quality research is critical to produce the clinical practices and policies necessary to reduce the burden of cardiovascular diseases in Saudi Arabia