Optimization of an ether series of mGluR5 positive allosteric modulators: Molecular determinants of MPEP site interaction crossover

We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) pos. allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topol. similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site.

Characterization of RSOA modulators in radio over fiber links

In this work physical and behavioral models for a bulk Reflective Semiconductor Optical Amplifier (RSOA) modulator in Radio over Fiber (RoF) links are proposed. The transmission performance of the RSOA modulator is predicted under broadband signal drive. At first, the simplified physical model for the RSOA modulator in RoF links is proposed, which is based on the rate equation and traveling-wave equations with several assumptions. The model is implemented with the Symbolically Defined Devices (SDD) in Advanced Design System (ADS) and validated with experimental results. Detailed analysis regarding optical gain, harmonic and intermodulation distortions, and transmission performance is performed. The distribution of the carrier and Amplified Spontaneous Emission (ASE) is also demonstrated. Behavioral modeling of the RSOA modulator is to enable us to investigate the nonlinear distortion of the RSOA modulator from another perspective in system level. The Amplitude-to-Amplitude Conversion (AM-AM) and Amplitude-to-Phase Conversion (AM-PM) distortions of the RSOA modulator are demonstrated based on an Artificial Neural Network (ANN) and a generalized polynomial model. Another behavioral model based on Xparameters was obtained from the physical model. Compensation of the nonlinearity of the RSOA modulator is carried out based on a memory polynomial model. The nonlinear distortion of the RSOA modulator is reduced successfully. The improvement of the 3rd order intermodulation distortion is up to 17 dB. The Error Vector Magnitude (EVM) is improved from 6.1% to 2.0%. In the last part of this work, the performance of Fibre Optic Networks for Distributed and Extendible Heterogeneous Radio Architectures and Service Provisioning (FUTON) systems, which is the four-channel virtual Multiple Input Multiple Output (MIMO), is predicted by using the developed physical model. Based on Subcarrier Multiplexing (SCM) techniques, four-channel signals with 100 MHz bandwidth per channel are generated and used to drive the RSOA modulator. The transmission performance of the RSOA modulator under the broadband multi channels is depicted with the figure of merit, EVM under di erent adrature Amplitude Modulation (QAM) level of 64 and 254 for various number of Orthogonal Frequency Division Multiplexing (OFDM) subcarriers of 64, 512, 1024 and 2048.

Nutrition and farming practices as modulators of quality in gilthead seabream (Sparus aurata)

Gilthead seabream is the most important farmed species in the Mediterranean, and knowledge on how common farming practices impact its quality is limited. As such, this Thesis aimed to evaluate how gilthead seabream flesh quality is affected by some of these practices. In Chapter 2, the influence of nutritional factors was evaluated, specifically the high replacement of traditional marine-derived ingredients, both fishmeal and fish oil, with vegetable sources. We have seen that the vegetable-based diets tested did not greatly impact seabream flesh quality, although some alterations were seen in the fatty acid profile of the muscle. However, and despite having caused no alterations in flesh texture, vegetable ingredients reduced the amount of sulphated glycosaminoglycans in the extracellular matrix, affected muscle pH and reduced the activity of proteolytic enzymes. Throughout this Thesis, we measured for the first time the activity of proteolytic enzymes in seabream muscle, and cathepsin B was found to play a pivotal role in post-mortem muscle degradation. In Chapter 3, we evaluated the effect of harvesting and slaughter stress on seabream quality, and contrary to what is seen in most farmed species, our results show that gilthead seabream muscle structure is highly resistant to changes caused by stressful events. Nonetheless, considering that welfare is an increasingly important quality criterion, the use of a zero-withdrawal anaesthetic as a rested harvest technique or even slaughter method could prove valuable to the industry. In Chapter 4, we used maslinic acid as a dietary supplement, to modulate the muscle’s energetic status pre-mortem. As a finishing strategy, maslinic acid failed to increase levels of glycogen and ATP in the muscle. However, supplementation resulted in higher muscle fibre diameter and lower cathepsin B activity, and maslinic acid is likely to be useful to promote growth in this species. In general our Thesis has generated new knowledge to a major challenge facing the aquaculture industry, which is to find a compromise between the trends towards intensive rearing and consumer demand for healthy, high quality seafood being ethically acceptable and having a low impact on the environment.

Methods for the transfer function design of multiple narrow-band bandpass sigma-delta modulators

This paper presents the design analysis of novel tunable narrow-band bandpass sigma-delta modulators, which can achieve concurrent multiple noise-shaping for multi-tone input signals. Four different design methodologies based on the noise transfer functions of comb filters, slink filters, multi-notch filters and fractional delay comb filters are applied for the design of these multiple-band sigma-delta modulators. The latter approach utilises conventional comb filters in conjunction with FIR, or allpass IIR fractional delay filters, to deliver the desired nulls for the quantisation noise transfer function. Detailed simulation results show that FIR fractional delay comb filter-based sigma-delta modulators tune accurately to most centre frequencies, but suffer from degraded resolution at frequencies close to Nyquist. However, superior accuracies are obtained from their allpass IIR fractional delay counterpart at the expense of a slight shift in noise-shaping bands at very high frequencies. The merits and drawbacks of each technique for the various sigma-delta topologies are assessed in terms of in-band signal-to-noise ratios, accuracy of tunability and coefficient complexity for ease of implementation.

Narrow-band variable center frequency single-loop and multistage sigma-delta modulators for bandpass signals

Oversampled narrow-band single-loop and multistage resonator-based bandpass sigma-delta (Σ-Δ) modulators that can accommodate different passband center to sampling frequency ratios are reported. These tunable bandpass configurations are designed by analytically determining and subsequently verifying through detailed empirical simulations the required compensation hardware to deliver enhanced noise-shaping. It is demonstrated that comparatively superior in-band signal-to-noise ratios and dynamic ranges are attributed to the inclusion of appropriate digital feedforward and feedback compensators within these structures.

Application of fractional delay filters to tune the centre frequency location of single-band sigma-delta modulators

This paper presents a novel technique for the design of narrow-band sigma-delta modulators with an embedded tunable centre frequency mechanism. This method demonstrates that the use of sum filters combined with a fractional delayer provide the flexibility of tuning the noise shaping band for any desired variable centre frequency input signal.

A comparative study of complex multiple-band noise-shaping sigma-delta modulators for multi-tone input signals

This paper presents a comparative study of complex single-bit and multi-bit sigma-delta modulators that are capable of providing concurrent multiple-band noise-shaping for multi-tone narrow-band input signals. The concepts applied for the three design methodologies are based on the noise transfer functions of complex comb, complex slink and complex multi-notch filters.

Increasing the variability of centre frequency locations in multiple-band sigma-delta modulators via the use of fractional delay filters

This paper presents the design analysis of novel tunable narrow-band bandpass sigma-delta modulators, that can achieve concurrent multiple noise-shaping for multi-tone input signals. This approach utilises conventional comb filters in conjunction with FIR, or allpass IIR fractional delay filters, to deliver the desired nulls for the quantisation noise transfer function. Detailed simulation results show that FIR fractional delay comb filter based sigma-delta modulators tune accurately to most centre frequencies, but suffer from degraded resolution at frequencies close to Nyquist. However, superior accuracies are obtained from their allpass IIR fractional delay counterpart at the expense of a slight shift in noise-shaping bands at very high frequencies.

Tunable centre frequency resonator based bandpass Σ-Δ modulators

This paper presents a methodology for the design of oversampled narrow-band single-loop and multi-stage resonator-based bandpass Σ-Δ modulators that can accommodate different passband centre to sampling frequency ratios. These tunable bandpass configurations are designed by analytically determining the required compensation hardware to deliver good resolution. Thorough simulations demonstrate that comparatively superior in-band signal-to-noise ratios (SNRs) and dynamic ranges (DRs) are attributed to the inclusion of appropriate feedforward and feedback compensators within these structures.

Effective-fourth-order resonator based MASH bandpass sigma-delta modulators

Two novel effective-fourth-order (eighth-order) resonator based MASH (MultistAge noise SHaping) bandpass Σ-Δ modulators are introduced at the behavioural level and subsequently examined by simulations utilising the ALTA SPW environment. The considered bandpass configurations have in their loop filter a cascade of standard second-order resonator structures in order to achieve appropriate noise shaping. The quantisation noise in each stage is suppressed by feeding the error of each section into the input of the following stage. It is demonstrated in this paper that the quadruple effective-first-order cascade configuration has significantly better performance as well as conforming more closely with theory in comparison with the effective-second-order effective-second-order cascade. The superior performance of the former can be attributed to the cumulative effect of the multi-bit outputs as well as the presence of more notch filters.