Applications of CRISPR for musculoskeletal research

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice

Surface phonon polaritonics made simple: Great as plasmonics but lower losses

Phonon-polaritons offer an exciting avenue in nanophotonics. We comment on the novel nanofabrication approach presented by Bo Qiang et al. in this issue of Advanced Photonics. Their approach to phononic material allows better radiation manipulation, and high Q-factors

Twist Angle Tuning of Moir\ue9 Exciton Polaritons in van der Waals Heterostructures

Twisted atomically thin semiconductors are characterized by moir\ue9 excitons. Their optical signatures and selection rules are well understood. However, their hybridization with photons in the strong coupling regime for heterostructures integrated in an optical cavity has not been the focus of research yet. Here, we combine an excitonic density matrix formalism with a Hopfield approach to provide microscopic insights into moir\ue9 exciton polaritons. In particular, we show that exciton-light coupling, polariton energy, and even the number of polariton branches can be controlled via the twist angle. We find that these new hybrid light-exciton states become delocalized relative to the constituent excitons due to the mixing with light and higher-energy excitons. The system can be interpreted as a natural quantum metamaterial with a periodicity that can be engineered via the twist angle. Our study presents a significant advance in microscopic understanding and control of moir\ue9 exciton polaritons in twisted atomically thin semiconductors

The microbial ecology of anaerobic digestion: characterising novel biogas configurations through molecular and statistical methods

The microbiological generation of methane from organic substrates is a process with incredible flexibility, which has allowed continual innovations in its application as a source of renewable energy. Ireland’s renewable energy sector is gradually expanding, and although biogas is as-yet a minor component, it currently presents an opportunity to capitalise on prevalent feedstocks and existing gaps in the country’s energy infrastructure. In order for anaerobic digestion to succeed in this context, several criteria need to be optimised, particularly improving process stability and yields in order to make the technology competitive and deliver on the promise of biogas. Despite the efforts to harness anaerobic digestion as a sustainable energy technology, it remains a microbial phenomenon which is incompletely characterised and difficult to scale to industrial requirements. Indeed, many applications of anaerobic digestion for biogas require microbial communities to endure sustained stresses (high organic loading rates, high concentrations of inhibitive breakdown products, high temperatures) which can further destabilise the process and make certain configurations appear unfeasible. An alternative application of anaerobic digestion focuses on a subset of the biogas community (the methanogenic archaea) to convert supplies of CO2 and H2 to biomethane at efficiencies approaching natural gas production (i.e. near-pure methane). This technology is highly attractive as it could allow conversion of both exogenous/industrially-produced H2 and CO2 to biomethane, as well as upgrading the methane content of ‘raw’ biogas. However, addition of hydrogen to anaerobic communities can paradoxically prevent biogas formation, by disrupting the finely-balanced thermodynamics of fermentation. It has been suggested that to avoid the inhibition caused by adding hydrogen to the microbial community in situ, methanogens could be cultured and fed CO2 and H2 in a specialised ex situ reactor, independent of feedstock hydrolysis and fermentation. Although hydrogenotrophic methanogens are autotrophs and can fix CO2 to cellular material, it has not been clear what sort of x microbial communities are encouraged by upgrading setups, nor is it clear how the supply of H2 disrupts the biogas community. This thesis explores the microbial ecology underlying several anaerobic digestion configurations relevant to renewable energy production in both Irish and international contexts. Microbial community structures were considered in relation to feedstock composition and biogas output, and shifts in the abundance of functional microbial populations were related to changes in reactor environment and biomethane output, thereby identifying factors which appear to inhibit or support biogas production in these novel setups. Chapters 2 and 3 consider anaerobic digestion of feedstocks which represent promising biogas resources in Ireland and beyond (seaweed/dairy slurry and grass silage/dairy slurry respectively), but can be recalcitrant or problematic for digestion due to their compositions. In both chapters, next-generation sequencing of 16S microbial community profiles clearly indicates disruption between the metabolism of end-fermentation products and subsequent methanogenesis when operated at relatively high loading rates of substrate (2-3kgVSm-3d -1 ). In the case of seaweed/dairy slurry digestion (chapter 2), large quantities of seaweed release excess ammonia, correlating with collapse of the methanogen populations (acetoclastic Methanosarcina) necessary to metabolise accumulating acetate, ultimately leading to reactor failure. In the case of grass silage/dairy slurry digestion, high organic loading of grass silage appears to inhibit or exhaust fermenting bacteria (Clostridia), as shown through a supplementation regime which restores process function and increases abundance of fermenting bacteria. Surprisingly, this treatment does not encourage archaeal populations (Methanobacterium), and may even reduce their abundance. In both chapters, conditions which inhibit biogas production lead to microbial communities which are distinct from those seen when inhibition was resolved. xi Chapters 4 and 5 explore biogas upgrading communities, charting how these communities relate to variables in the upgrading process. Chapter 4 characterises the microbial community in a minimal example of ex situ biogas upgrading at two thermophilic temperatures (55°C, 65°C), demonstrating the persistence and stability of methanogen populations (in particular, the family Methanobacteriaceae) alongside a surprisingly complex bacterial community. Chapter 5 expands on this finding, comparing the upgrading communities between in situ and ex situ operation during increasing flow rates of H2, showing that the presence (in situ) or absence (ex situ) of feedstock delineates these communities. This in turn governs community response to rates of H2 supply, with in situ communities showing a far greater susceptibility to inhibition, population flux, and displacement of methanogens (Methanothermobacter). In comparison, ex situ upgrading communities saw little change at much higher H2 flow rates, and instead encouraged larger populations of closely related methanogens (Methanobacterium). These large ex situ hydrogenotrophic populations were significantly associated with smaller, ‘satellite’ populations of hydrogen-producing bacteria, indicating a thermophilic upgrading community centred on biogas metabolism

Cavity optomechanics with photonic bound states in the continuum

We propose a versatile, free-space cavity optomechanics platform built from two photonic crystal membranes, one of which is freely suspended, and designed to form a microcavity less than one wavelength long. This cavity features a series of photonic bound states in the continuum that, in principle, trap light forever and can be favorably used together with evanescent coupling for realizing various types of optomechanical couplings, such as linear or quadratic coupling of either dispersive or dissipative type, by tuning the photonic crystal patterning and cavity length. Crucially, this platform allows for a quantum cooperativity exceeding unity in the ultrastrong single-photon coupling regime, surpassing the performance of conventional Fabry-Perot-based cavity optomechanical devices in the nonresolved sideband regime. This platform allows for exploring new regimes of the optomechanical interaction, in particular in the framework of pulsed and single-photon optomechanics

Signatures of dark excitons in exciton-polariton optics of transition metal dichalcogenides

Integrating 2D materials into high-quality optical microcavities opens the door to fascinating many-particle phenomena including the formation of exciton-polaritons. These are hybrid quasi-particles inheriting properties of both the constituent photons and excitons. In this work, we investigate the so-far overlooked impact of dark excitons on the momentum-resolved absorption spectra of hBN-encapsulated WSe$_2$ and MoSe$_2$ monolayers in the strong-coupling regime. In particular, thanks to the efficient phonon-mediated scattering of polaritons into energetically lower dark exciton states, the absorption of the lower polariton branch in WSe$_2$ is much higher than in MoSe$_2$. It shows unique step-like increases in the momentum-resolved profile indicating opening of specific scattering channels. We study how different externally accessible quantities, such as temperature or mirror reflectance, change the optical response of polaritons. Our study contributes to an improved microscopic understanding of exciton-polaritons and their interaction with phonons, potentially suggesting experiments that could determine the energy of dark exciton states via momentum-resolved polariton absorption.Comment: 10 pages, 5 figure

Visual categorization and the parietal cortex

The primate brain is adept at rapidly grouping items and events into functional classes, or categories, in order to recognize the significance of stimuli and guide behavior. Higher cognitive functions have traditionally been considered the domain of frontal areas. However, increasing evidence suggests that parietal cortex is also involved in categorical and associative processes. Previous work showed that the parietal cortex is highly involved in spatial processing, attention, and saccadic eye movement planning, and more recent studies have found decision-making signals in lateral intraparietal area (LIP). We recently found that a subdivision of parietal cortex, LIP, reflects learned categories for multiple types of visual stimuli. Additionally, a comparison of categorization signals in parietal and frontal areas found stronger and earlier categorization signals in parietal cortex arguing that, in trained animals, parietal abstract association or category signals are unlikely to arise via feedback from prefrontal cortex (PFC)

Exciton optics, dynamics, and transport in atomically thin semiconductors

Atomically thin semiconductors such as transition metal dichalcogenide (TMD) monolayers exhibit a very strong Coulomb interaction, giving rise to a rich exciton landscape. This makes these materials highly attractive for efficient and tunable optoelectronic devices. In this Research Update, we review the recent progress in the understanding of exciton optics, dynamics, and transport, which crucially govern the operation of TMD-based devices. We highlight the impact of hexagonal boron nitride-encapsulation, which reveals a plethora of many-particle states in optical spectra, and we outline the most novel breakthroughs in the field of exciton-polaritonics. Moreover, we underline the direct observation of exciton formation and thermalization in TMD monolayers and heterostructures in recent time-resolved, angle-resolved photoemission spectroscopy studies. We also show the impact of exciton density, strain, and dielectric environment on exciton diffusion and funneling. Finally, we put forward relevant research directions in the field of atomically thin semiconductors for the near future