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Particle accelerators driven by laser-generated terahertz (THz) pulses promise unprecedented control over the energy–time phase space of particle bunches compared with conventional radiofrequency technology. Here we demonstrate acceleration of a relativistic electron beam in a THz-driven linear accelerator. Narrowband THz pulses were tuned to the phase-velocity-matched operating frequency of a rectangular dielectric-lined waveguide for extended collinear interaction with 35 MeV, 60 pC electron bunches, imparting multicycle energy modulation to chirped (6 ps) bunches and injection phase-dependent energy gain (up to 10 keV) to subcycle (2 ps) bunches. These proof-of-principle results establish a route to whole-bunch linear acceleration of subpicosecond particle beams, directly applicable to scaled-up and multistaged concepts capable of preserving beam quality, thus marking a key milestone for future THz-driven acceleration of relativistic beams.Relativistic 35 MeV electron bunches with charges of 60 pC are accelerated in a terahertz-wave-driven dielectric waveguide. When the terahertz pulse energy is 0.8 μJ, an accelerating gradient of 2 MeV m−1 and energy gain of 10 keV are achieved.

Staged acceleration, driven by terahertz (THz) frequency radiation pulses in a lattice with alternating orientation dielectric-lined waveguides and intervening matching optics, is shown to mitigate transverse emittance and energy spread growth, opening a route to multistage THz linacs. Decomposition of the longitudinal THz field into the multipolar components reveals a quadrupole field component with strong radial dependence. As such, it induces a transverse energy correlation in the beam during acceleration due to the large variation in the electric field with radius and azimuthal position of the electrons. An alternating orientation of stages separated by a matching section provides a compensation of transverse energy spread correlation induced in the beam during its interaction with the THz field. Furthermore, the monopolar component of the acceleratingLSM11mode was found to be constant with respect to transverse position, entailing zero monopolar transverse voltage and preventing emittance growth, unlike conventional radio-frequency structures. We demonstrate in a rectangular dielectric-lined waveguide structure that, when used for the acceleration of relativistic electrons, the slice transverse emittance is conserved and the growth in the slice energy spread is reduced by 70%–80% simultaneously over a system of two stages, each providing an interaction length of 4 mm and an energy gain of up to 2 MeV.

Laser-plasma wakefield acceleration (LWFA) offers ultrahigh accelerating gradients in compact setups, but the complex non-linear nature of the process makes it challenging to generate high-quality beams. Injection of electron bunches from an external source into a plasma accelerator provides a promising route to improved performance; however, electron bunches from conventional radio-frequency (RF)-based injectors suffer from non-linear compression and laser-beam asynchrony, leading to energy jitter and emittance growth. We present a fundamental concept of terahertz-controlled electron bunches for external injection into LWFA. This terahertz-frequency approach provides temporal locking between the electron beam and the drive laser, and enables the compression of high-quality beams to sub-10-fs durations before injection into the LWFA. Numerical simulations demonstrate that GeV-scale acceleration with excellent beam quality and stability -- energy jitter and energy spread around 0.2% -- can be achieved using this method. This concept opens new opportunities for stable, multi-stage laser-driven accelerators and supports the development of next-generation applications such as free-electron lasers (FELs).

We demonstrate that narrowband multi-cycle terahertz (MC-THz) sources based on periodically-poled lithium niobate (PPLN) wafer stacks can be driven by high repetition-rate, high energy femtosecond ytterbium-doped lasers. Operating at 10-kHz repetition rate with up to 104 W of pump power on a 10-wafer stack, we measure 26.4 mW of THz average power for a narrowband multi-cycle source. We identify and quantify strong lensing effects causing dramatic beam focusing in 47 wafer stacks which act as a primary limitation in the current configuration, and present mitigation strategies for future scaling. This first study of high average power narrowband multi-cycle THz sources offers a path forward to Watt-level high repetition rate sources using thin lithium niobate plates.

Femtosecond relativistic electron bunches and micro-bunch trains synchronised with femtosecond precision to external laser sources are widely sought for next-generation accelerator and photonic technologies, from extreme UV and X-ray light sources for materials science, to ultrafast electron diffraction and future high-energy physics colliders. While few-femtosecond bunches have been demonstrated, achieving the control, stability and femtosecond-level laser synchronisation remains critically out of reach. Here we demonstrate a concept for laser-driven compression of high-energy (35.5 MeV) electron bunches with temporal synchronisation to a high-power (few-TW) laser system. Laser-generated multi-cycle terahertz (THz) pulses drive periodic electron energy modulation, enabling subsequent magnetic compression capable of generating tuneable picosecond-spaced bunch trains with 30 pC total charge and 50 A peak currents, or to compress a single bunch by a factor of 27 down to 15 fs duration. The THz-driven compression simultaneously drives temporal-locking of the bunch to the THz drive laser, providing a route to femtosecond-level synchronisation, overcoming the timing jitter inherent to radio-frequency accelerators and high-power laser systems. This THz technique offers compact and flexible bunch control with unprecedented temporal synchronisation, opening a pathway to unlock new capabilities for free electron lasers, ultrafast electron diffraction and novel plasma accelerators.

The research presented in this thesis concentrates on the optical properties of InGaN/GaN and AlGaN/GaN quantum well structures. A study of the low temperature (T=6 K) optical properties of a series of InGaN/GaN single quantum well structures with varying indium fractions is presented. With increasing indium fraction the strength of the exciton/LO phonon coupling increases. The Huang-Rhys factors extracted from the photoluminescence spectra were compared with the results of model calculations, yielding a value of approximately 20 Å for the in-plane localisation length scale of carriers. This value was comparable with the in-plane extent of the well width fluctuations identified in microstructural studies. The optical properties of two InGaN/GaN single quantum well structures were studied under resonant excitation conditions. The low temperature photoluminescence spectra showed a broad recombination feature that was attributed to acoustic phonon accompanied absorption and emission from a distribution of localised states. Comparing the form of the spectra with model calculations, where the deformation potential coupling of carriers to an effectively continuous disfribution of acoustic phonons was considered, suggested that the in-plane localisation length scale of carriers may be as small as 2.5 Å. The low temperature and temperature dependent optical properties of a series of 10- period InGaN/GaN multiple quantum well structures with varying indium fractions were studied. A deterioration of the room temperature internal photoluminescence quantum efficiency was found for the structures with the largest indium fractions. Two possible explanations for this deterioration were investigated. First, the issue of critical stack thickness was investigated in a series of high indium content InGaN/GaN quantum well structures with 1,3,5,7 and 10 periods. No greater deterioration of the optical properties was found with increasing numbers of quantum wells. Second, the influence of the barrier growth temperature/method on the optical properties of high indium content InGaN/GaN multiple quantum well structures is reported. These results indicated that the barrier growth temperature/method also influenced the quantum well width. Consequently, the observed improvement in the optical properties could not solely be attributed to the change in the barrier material quality. Finally, the low temperature and temperature dependent optical properties of a series of Al0.2Ga0.8N/GaN multiple quantum well structures with varying well width were studied. The relatively poor room temperature internal photoluminescence quantum efficiencies obtained for these structures was discussed both in terms of the delocalisation of carriers at room temperature and the influence of the quantum well parameters. The latter was investigated further, via the study of a series of Al0.5Ga0.5N/GaN multiple quantum well structures with varying well width. The results suggested that the poor room temperature internal photoluminescence quantum efficiencies are inherent to AlGaN/GaN quantum well structures. A third possible explanation, relating to the oxygen contamination of the AlGaN material, was proposed.

Dielectric structures driven by laser-generated terahertz (THz) pulses may hold the key to overcoming the technological limitations of conventional particle accelerators and with recent experimental demonstrations of acceleration, compression and streaking of low-energy (sub-100 keV) electron beams, operation at relativistic beam energies is now essential to realize the full potential of THz-driven structures. We present the first THz-driven linear acceleration of relativistic 35 MeV electron bunches, exploiting the collinear excitation of a dielectric-lined waveguide driven by the longitudinal electric field component of polarization-tailored, narrowband THz pulses. Our results pave the way to unprecedented control over relativistic electron beams, providing bunch compression for ultrafast electron diffraction, energy manipulation for bunch diagnostics, and ultimately delivering high-field gradients for compact THz-driven particle acceleration.

RNA interference (RNAi)-related pathways target viruses and transposable element (TE) transcripts in plants, fungi, and ecdysozoans (nematodes and arthropods), giving protection against infection and transmission. In each case, this produces abundant TE and virus-derived 20-30nt small RNAs, which provide a characteristic signature of RNAi-mediated defence. The broad phylogenetic distribution of the Argonaute and Dicer-family genes that mediate these pathways suggests that defensive RNAi is ancient, and probably shared by most animal (metazoan) phyla. Indeed, while vertebrates had been thought an exception, it has recently been argued that mammals also possess an antiviral RNAi pathway, although its immunological relevance is currently uncertain and the viral small RNAs (viRNAs) are not easily detectable. Here we use a metagenomic approach to test for the presence of viRNAs in five species from divergent animal phyla (Porifera, Cnidaria, Echinodermata, Mollusca, and Annelida), and in a brown alga-which represents an independent origin of multicellularity from plants, fungi, and animals. We use metagenomic RNA sequencing to identify around 80 virus-like contigs in these lineages, and small RNA sequencing to identify viRNAs derived from those viruses. We identified 21U small RNAs derived from an RNA virus in the brown alga, reminiscent of plant and fungal viRNAs, despite the deep divergence between these lineages. However, contrary to our expectations, we were unable to identify canonical (i.e. Drosophila- or nematode-like) viRNAs in any of the animals, despite the widespread presence of abundant micro-RNAs, and somatic transposon-derived piwi-interacting RNAs. We did identify a distinctive group of small RNAs derived from RNA viruses in the mollusc. However, unlike ecdysozoan viRNAs, these had a piRNA-like length distribution but lacked key signatures of piRNA biogenesis. We also identified primary piRNAs derived from putatively endogenous copies of DNA viruses in the cnidarian and the echinoderm, and an endogenous RNA virus in the mollusc. The absence of canonical virus-derived small RNAs from our samples may suggest that the majority of animal phyla lack an antiviral RNAi response. Alternatively, these phyla could possess an antiviral RNAi response resembling that reported for vertebrates, with cryptic viRNAs not detectable through simple metagenomic sequencing of wild-type individuals. In either case, our findings show that the antiviral RNAi responses of arthropods and nematodes, which are highly divergent from each other and from that of plants and fungi, are also highly diverged from the most likely ancestral metazoan state.

Deaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups. We used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording. In this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL.

Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities.High-throughput biocatalytic screening and metagenomics have been used to discover over 300 imine reductases (IREDs) and subsequently produce a sequence-diverse panel of IREDs suitable for optimizing the synthesis of chiral amines. Additional characterization identified biocatalysts that accommodate structurally demanding amines and ketones for enzymatic reductive aminations.