Identification of candidate genes for dyslexia susceptibility on chromosome 18

Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. Methodology/Principal Findings: Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L). Conclusions: Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.

A simple, sensitive and selective quantum-dot-based western blot method for the simultaneous detection of multiple targets from cell lysates

Quantum dots (Qdots) are fluorescent nanoparticles that have great potential as detection agents in biological applications. Their optical properties, including photostability and narrow, symmetrical emission bands with large Stokes shifts, and the potential for multiplexing of many different colours, give them significant advantages over traditionally used fluorescent dyes. Here, we report the straightforward generation of stable, covalent quantum dot-protein A/G bioconjugates that will be able to bind to almost any IgG antibody, and therefore can be used in many applications. An additional advantage is that the requirement for a secondary antibody is removed, simplifying experimental design. To demonstrate their use, we show their application in multiplexed western blotting. The sensitivity of Qdot conjugates is found to be superior to fluorescent dyes, and comparable to, or potentially better than, enhanced chemiluminescence. We show a true biological validation using a four-colour multiplexed western blot against a complex cell lysate background, and have significantly improved previously reported non-specific binding of the Qdots to cellular proteins.

Synthesis and evaluation of novel ligands for quantum dot stabilisation and polymerisation studies

This thesis describes the design and synthesis of a variety of functionalised phosphine oxides and sulfides, based on the structure of trioctylphosphine oxide, synthesised for the purpose of surface modification of quantum dots. The ability of the ligands to modify the surface chemistry via displacement of the original hexadecylamine capping layer of quantum dots was evaluated. Finally the surface modified quantum dots were investigated for enhancement in their inherent properties and improved compatibility with the various applications for which they were initially designed. Upon the commencement of research involving quantum dots it became apparent that more information on their behaviour and interaction with the environment was required. The limits of the inherent stability of hexadecylamine capped quantum dots were investigated by exposure to a number of different environments. The effect upon the stability of the quantum dots was monitored by changes in the photoluminescence ability of their cores. Subtle differences between different batches of quantum dots were observed and the necessity to account for these in future applications noted. Lastly the displacement of the original hexadecylamine coating with the "designer" functionalised ligands was evaluated to produce a set of conditions that would result in the best possible surface modification. A general procedure was elucidated however it was discovered that each displacement still required slight adjustment by consideration of the other factors such as the difference in ligand structure and the individuality of the various batches of quantum dots. This thesis also describes a procedure for the addition of a protective layer to the surface of quantum dots by cross-linking the functionalised ligands bound to the surface via an acyclic diene metathesis polymerisation. A detailed description of the problems encountered in the analysis of these materials combined with the use of novel techniques such as diffusion ordered spectroscopy is provided as a means to overcome the limitations encountered. Finally a demonstration of the superior stability, upon exposure to a range of aggressive environments of these protected materials compared with those before cross-linking provided physical proof of the cross-linking process and the advantages of the cross-linking modification. Finally this thesis includes the presentation of initial work into the production of luminescent nanocrystal encoded resin beads for the specific use in solid phase combinatorial chemistry. Demonstration of the successful covalent incorporation of quantum dots into the polymeric matrices of non-functionalised and functionalised resin beads is described. Finally by preliminary work to address and overcome the possible limitations that may be encountered in the production and general employment of these materials in combinatorial techniques is given.

Filter assisted wavelength conversion with quantum-dot SOAs

The nonlinear operation regimes of quantum-dot semiconductor optical amplifiers (QD-SOAs) are investigated and the ideal filter providing the best all-optical wavelength conversion efficiency is derived theoretically. Results are confirmed by experiments with Q2-factors amounting to 16 dB.

Quantum-dot mode-locked lasers with dual-mode optical injection

Quantum-dot mode-locked lasers are injection-locked by coherent two-tone master sources. Spectral tuning, significantly improved time-bandwidth product, and low jitter are demonstrated without deterioration of the pulse properties.

Dynamics of quantum-dot mode-locked lasers with optical injection

We present the dynamics of quantum-dot passively mode-locked semiconductor lasers under optical injection. We discuss the benefits of various configurations of the master source including single, dual, and multiple coherent frequency sources. In particular, we demonstrate that optical injection can improve the properties of the slave laser in terms of time-bandwidth product, optical linewidth, and timing jitter.

Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia

Aim: Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia. Method: Genome-wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with speech and language deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17 years), and a set of individuals with dyslexia (314 probands: 224 males, 90 females; age range 7 to 18 years). Results: In the clinical language-impaired cohort, three abnormal karyotypic results were identified in probands (proband yield 3.4%). In the SLI replication cohort, six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome), and one unresolved karyotype were identified. Interpretation: The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.25%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems and normal non-verbal IQ. Early detection of these aneuploidies can provide information and direct the appropriate management for individuals. © 2013 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

Quantum-dot mode-locked lasers with dual-mode optical injection

Quantum-dot mode-locked lasers are injection-locked by coherent two-tone master sources. Spectral tuning, significantly improved time-bandwidth product, and low jitter are demonstrated without deterioration of the pulse properties.

Changes in neural complexity during the perception of 3D images using random dot stereograms

One developing theme in consciousness research is that consciousness is not the product of any specific component of the brain, rather it is an emergent property of the changing patterns of connectivity between different specialised functional components. For example, the dynamic core hypothesis proposes that conscious experience requires high levels of neural complexity, where complexity is defined in terms of functional connectivity. To test this hypothesis, electroencephalography was recorded while participants were shown random dot-stereograms. Consistent with the dynamic core hypothesis, neural complexity increased as the participants changed from simply viewing the stereogram to consciously perceiving the hidden 3D image.

Tunable master-oscillator power-amplifier based on chirped quantum-dot structures

A broadly tunable master-oscillator power-amplifier (MOPA) picosecond optical pulse source is demonstrated, consisting of an external cavity passively mode-locked laser diode with a tapered semiconductor amplifier. By employing chirped quantum-dot structures on both the oscillator's gain chip and amplifier, a wide tunability range between 1187 and 1283 nm is achieved. Under mode-locked operation, the highest output peak power of 4.39 W is achieved from the MOPA, corresponding to a peak power spectral density of 31.4 dBm/nm. © 1989-2012 IEEE.

202nm continuous tuning from high-power external-cavity InAs/GaAs quantum-dot laser

Record broadly tunable high-power external cavity InAs/GaAs quantum-dot diode laser is demonstrated. A maximum output power of 455mW and a side-mode suppression ratio >45dB in the central part of the tuning range are achieved. ©2010 IEEE.

Broadly tunable CW green-to-red laser source based on frequency doubling of a quantum-dot external cavity diode laser in a PPKTP waveguide

Here we present a compact tunable all-room-temperature frequency-doubling scheme, using a periodically poled potassium titanyl phosphate (PPKTP) waveguide and a QD-ECDL. A broad wavelength tunability of the second harmonic generated light (SHG) in the spectral region between 567.7 and 629.1 nm was achieved, with maximum conversion efficiencies in range of 0.34%-7.9%. The maximum output power for the SHG light was 4.11 mW at 591.5 nm, achieved for 52 mW of launched pump power at 1183 nm, resulting in a conversion efficiency of 7.9%.

Generation of orange light from a PPKTP waveguide end-pumped by a quantum-dot tuneable laser

Here we present a compact all-room-temperature frequency-doubling scheme generating orange light, using a PPKTP waveguide and a quantum-dot external cavity diode laser (QD-ECDL). The maximum output power for the second harmonic generated light (SHG) was 1.43 mW at 613 nm, achieved for 70 mW of launched pump power at 1226 nm. This represents an important step towards a compact and wall-plug-efficient coherent orange light source, operating at room temperature.

High-power spectral bistability in a multi-section quantum-dot laser under continuous-wave or mode-locked operation

Wavelength bistability between 1245nm and 1295nm is demonstrated in a multi-section quantum-dot laser, controlled via the reverse bias on the saturable absorber. Continuous-wave or mode-locked regimes are achieved (output power up to 25mW and 17mW). © OSA/CLEO 2011.

Quantum dot materials for ultrafast optoelectronics

The report discussed on a new high performance quantum dot based laser sources which demonstrated a record-high peak power and subpicosecond optical pulses in 1-1.3μm wavelength range.