Insulin gene therapy for the treatment of diabetes mellitus

Currently available treatments for insulin-dependent diabetes mellitus are often inadequate in terms of both efficacy and patient compliance. Gene therapy offers the possibility of a novel and improved method by which exogenous insulin can be delivered to a patient. This was approached in the present study by constructing a novel insulin-secreting cell line. For the purposes of this work immortalized cell lines were used. Fibroblasts and pituitary cells were transfected with the human preproisinulin gene to create stable lines of proinsulin- and insulin-secreting cells. The effect of known β-cell secretagogues on these cells were investigated, and found mostly to have no stimulatory effect, although IBMX, arginine and ZnSO4 each increased the rate of secretion. Cyclosporin (CyA) is currently the immunosuppresant of choice for transplant recipients; the effect of this treatment on endogenous β-cell function was assessed both in vivo and in vitro. Therapeutic doses of CyA were found to reduce plasma insulin concentrations and to impair glucose tolerance. The effect of immunoisolation on insulin release by HIT T15 cells was also investigated. The presence of an alginate membrane was found to severely impair insulin release. For the first implantation of the insulin-secreting cells, the animal model selected was the athymic nude mouse. This animal is immunoincompetent, and hence the use of an immunosuppressive regimen is circumvented. Graft function was assessed by measurement of plasma human C peptide concentrations, using a highly specific assay. Intraperitoneal implantation of genetically manipulated insulin-secreting pituitary cells into nude mice subsequently treated with a large dose of streptozotocin (STZ) resulted in a significantly delayed onset of hyperglycaemia when compared to control animals. Consumption of a ZnSO4 solution was shown to increase human C peptide release by the implant. Ensuing studies in nude mice examined the efficacy of different implantation sites, and included histochemical examination of the tumours. Aldehyde fuchsin staining and immunocytochemical processing demonstrated the presence of insulin containing cells within the excised tissue. Following initial investigations in nude mice, implantation studies were performed in CyA-immunosuppressed normal and STZ-diabetic mice. Graft function was found to be less efficacious, possibly due to the subcutaneous implantation site, or to the immunosuppresive regimen. Histochemical and transmission electron microscopic analysis of the tumour-like cell clusters found at autopsy revealed necrosis of cells at the core, but essentially normal cell morphology, with dense secretory granules in peripheral cells. The thesis provides evidence that gene therapy offers a feasibly new approach to insulin delivery.

Line-by-line fiber Bragg grating made by femtosecond laser

In this letter, we report on the inscription of a fourth-order fiber Bragg grating made line-by-line in the optical fiber using a femtosecond laser. Strong Bragg resonance (~17 dB) and low insertion loss (~0.5 dB) were obtained with only 2000 periods. Measured refractive index change of these inscribed lines reaches up to 7 × 10-3. The grating was fully characterized and the low insertion loss together with low polarization-dependent loss were realized compared to gratings made by the point-by-point method. The high temperature annealing experiment shows the grating can survive up to at least 800°C.

Iterative subspace analysis based on feature line distance

Nearest feature line-based subspace analysis is first proposed in this paper. Compared with conventional methods, the newly proposed one brings better generalization performance and incremental analysis. The projection point and feature line distance are expressed as a function of a subspace, which is obtained by minimizing the mean square feature line distance. Moreover, by adopting stochastic approximation rule to minimize the objective function in a gradient manner, the new method can be performed in an incremental mode, which makes it working well upon future data. Experimental results on the FERET face database and the UCI satellite image database demonstrate the effectiveness.

Polarization multiplexed 16QAM transmission employing modified digital back-propagation

We experimentally demonstrate performance enhancements enabled by weighted digital back propagation method for 28 Gbaud PM-16QAM transmission systems, over a 250 km ultra-large area fibre, using only one back-propagation step for the entire link, enabling up to 3 dB improvement in power tolerance with respect to linear compensation only. We observe that this is roughly the same improvement that can be obtained with the conventional, computationally heavy, non-weighted digital back propagation compensation with one step per span. As a further benchmark, we analyze performance improvement as a function of number of steps, and show that the performance improvement saturates at approximately 20 steps per span, at which a 5 dB improvement in power tolerance is obtained with respect to linear compensation only. Furthermore, we show that coarse-step self-phase modulation compensation is inefficient in wavelength division multiplexed transmission.

All-optical passive 2R regeneration of dispersion-managed RZ data at 40 and 80 Gbit/s using in-line NOLMs

We demonstrate that the use of in-line nonlinear optical loop mirrors (NOLMs) in dispersion-managed (DM) transmission systems dominated by amplitude noise can achieve passive 2R regeneration of a 40 and 80 Gbit/s RZ data stream. This is an indication that the use of this approach could obviate the need for full-regeneration in high data rate, strong DM systems, when intra-channel four-wave mixing poses serious problems.

Study of the operating regime for all-optical passive 2R regeneration of dispersion-managed RZ data at 40 Gb/s using in-line NOLMs

In this letter, we numerically demonstrate that the use of inline nonlinear optical loop mirrors in strongly dispersion-managed transmission systems dominated by pulse distortion and amplitude noise can achieve all-optical passive 2R regeneration of a 40-Gb/s return-to-zero data stream. We define the tolerance limits of this result to the parameters of the input pulses.

All-optical passive regeneration of 40 Gbit/s soliton data stream using dispersion management and in-line NOLMs

It is numerically demonstrated, for the first time, that dispersion management and in-line nonlinear optical loop mirrors can achieve all-optical passive regeneration and distance-unlimited transmission of a soliton data stream at 40 Gbit/s over standard fibre.

All-optical passive regeneration of 40 Gbit/s soliton data stream using dispersion-management and in-line nonlinear optical loop mirrors

We numerically demonstrate for the first time that dispersion management and in-line nonlinear optical loop mirrors can achieve all-optical passive regeneration and distance-unlimited transmission of a soliton data stream at 40 Gbit/s over standard fibre.

Optimal dispersion maps for multichannel soliton transmission with distributed Raman amplification

Using an asymptotic theory and a momentum method, we identify a family of dispersion management schemes with distributed Raman amplification, which are advantageous for massive multichannel soliton transmission. For the case of two-step dispersion maps, special schemes are found that have optimal (chirp-free) launch point locations that are independent of the fibre dispersion. Despite the variation of dispersion with wavelength due to the fibre dispersion slope, the transmission in several different channels can be optimized simultaneously using the same optimal launch point. The theoretical results are verified by direct numerical simulations.

On the theory of autosoliton propagation in optical fibers guided by in-line nonlinear devices

A theoretical model is developed to describe the propagation of ultra-short optical pulses in fiber transmission systems in the quasi-linear regime, with periodically inserted in-line lumped nonlinear optical devices. Stable autosoliton solutions are obtained for a particular application of the general theory.

Identification of optically clear regions of ternary polymer blends using a novel rapid screening method

The application of a rapid screening method for the construction of ternary phase diagrams is described for the first time, providing detailed visualization of phase boundaries in solvent-mediated blends. Our new approach rapidly identifies ternary blend compositions that afford optically clear materials, useful for applications where transparent films are necessary. The use of 96-well plates and a scanning plate reader has enabled rapid optical characterization to be carried out by transmission spectrophotometry (450 nm), whilst the nature and extent of crystallinity was examined subsequently by wide angle X-ray scattering (WAXS). The moderating effect of cellulose acetate butyrate can be visualized as driving the position of the phase boundaries in poly(l-lactic acid)/polycaprolactone (PLLA/PCL) blends. More surprisingly, the boundaries are critically dependent on the molecular weight of the crystallizable PLLA and PCL, with higher molecular weight polymers leading to blends with reduced phase separation. On the other hand, the propensity to crystallize was more evident in shorter chains. WAXS provides a convenient way of characterizing the contribution of the individual blend components to the crystalline regions across the range of blend compositions. © 2013 Society of Chemical Industry.

Evaluating the Capacity of Phase Modulator-Controlled Long-Haul Soliton Transmission

We review recent developments in the use of optical solitons for communication systems spanning transoceanic distances. The implementation of "soliton control" to alleviate the detrimental impact of effects such as amplifier noise is shown to be critical for obtaining advantages over competing technologies. The potential performance of two control strategies, namely straight line filtering and synchronous phase modulation, is examined in detail. Design diagrams are used to determine the maximum permissible amplifier spacing, which is a key determinant of system economics. To focus the enquiry, two example system spans are taken, representing transatlantic and transpacific distances. It is concluded that straight line filtering provides very little improvement over a basic design without control. However synchronous phase modulation, which may be implemented using a handful of actively driven components, provides very substantial benefits. These may be used either to extend the overall bit-rate-distance product of the system or to increase the amplifier spacing at more moderate capacities. © 1995 Academic Press. All rights reserved.

All-optical passive regeneration of 40 Gbit/s soliton data stream using dispersion management and in-line NOLMs

The feasibility of stable soliton transmission system was demonstrated using a practical dispersion map in conjunction with in-line nonlinear optical loop mirrors (NOLMs). The system's performance was examined at 40 Gbit/s data rate in terms of maximum propagation distance corresponding to a bit error rate of more than 10-9. The bit error rate was estimated by means of the standard Q-factor.

Efficient optimisation of per-channel pre-compensation in WDM 20-Gbit/s RZ-DPSK transmission in non-slope matched submarine links

We propose a computationally efficient method to the per-channel dispersion optimisation applied to 50 GHz-spaced N × 20-Gbit/s wavelength division multiplexing return-to-zero differential phase shift keying transmission in non-zero dispersion-shifted fibre based submarine systems. Crown Copyright © 2010.

Advanced techniques for the improvement of optical transmission systems

This thesis presents the experimental investigation into two novel techniques which can be incorporated into current optical systems. These techniques have the capability to improve the performance of transmission and the recovery of the transmitted signal at the receiver. The experimental objectives are described and the results for each technique are presented in two sections: The first experimental section is on work related to Ultra-long Raman Fibre lasers (ULRFLs). The fibre lasers have become an important research topic in recent years due to the significant improvement they give over lumped Raman amplification and their potential use in the development of system with large bandwidths and very low losses. The experiments involved the use of ASK and DPSK modulation types over a distance of 240km and DPSK over a distance of 320km. These results are compared to the current state of-the-art and against other types of ultra-long transmission amplification techniques. The second technique investigated involves asymmetrical, or offset, filtering. This technique is important because it deals with the strong filtering regimes that are a part of optical systems and networks in modern high-speed communications. It allows the improvement of the received signal by offsetting the central frequency of a filter after the output of a Delay Line Interferometer (DLI), which induces significant improvement in BER and/or Qvalues at the receiver and therefore an increase in signal quality. The experimental results are then concluded against the objectives of the experimental work and potential future work discussed.