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A reconfigurable arbitrary retarder array as complex structured matter
Get PDFTuneable retarder arrays, such as spatially patterned liquid crystal devices, have given rise to impressive photonic functionality, fuelling diverse applications ranging from microscopy and holography to encryption and communications. Presently these solutions are limited by the controllable degrees of freedom of structured matter, hindering applications that demand photonic systems with high flexibility and reconfigurable topologies. Here we demonstrate a compound modulator that implements a synthetic tuneable arbitrary retarder array as virtual pixels derived by cascading low functionality tuneable devices, realising full dynamic control of its arbitrary elliptical axis geometry, retardance value, and induced phase. Our approach offers unprecedented functionality that is user-defined and possesses high flexibility, allowing our modulator to act as a new beam generator, analyser, and corrector, opening an exciting path to tuneable topologies of light and matter
Short-term language switching training reveals an adaptive cerebellar network for bilingual language control
No full textPrevious studies have revealed that the cerebellum is involved in bilingual language control. In the present study, we further examined the cerebellum's role in bilingual language control and the plasticity of the cerebellar network using a training paradigm. Two groups of Chinese-English bilinguals performed the same language switching task in the pre-test and post-test sessions during functional magnetic resonance imaging scanning. After the pre-test, only the training group received an 8-day training in language switching. Results showed that bilingual language control was associated with a cerebellar network including multiple posterior cerebellar subregions as well as the anterior cerebellum (i.e., lobules IV-V). Furthermore, the cerebellar network exhibited adaptive changes with enhanced local neural efficiency and network connectivity after training. For the first time, our study revealed the plasticity of the cerebellar network in bilingual language control
Long term carbon export from mountain forests driven by hydroclimate and extreme event driven landsliding
Get PDFThe export of organic carbon from terrestrial ecosystems by erosion may play a central role in balancing the geological carbon cycle and Earth’s climate over millennial timescales. However, constraints on organic carbon yields have come from sampling modern rivers that don’t capture variation over decades to millennia driven by changing hydroclimate and erosion during extreme events. Here we use volumetric reconstructions of lake sedimentary fills to generate timeseries of sediment and organic carbon yields from two catchments draining the Southern Alps, New Zealand over the last millennium. The reconstructed yields indicate that earthquake-induced landslides significantly increase sediment and organic carbon yields, contributing to pulsed export that accounts for ~40% of the total. Between extreme events, organic carbon export increased twofold during centuries with a wetter reconstructed climate. Our findings suggest that the link between hydroclimate and organic carbon export may act as a negative feedback in the longer-term carbon cycle
Structural Evolution of Silicon Nitride Anodes during Electrochemical Lithiation
Get PDFSilicon nitride (SiN x ), a conversion-alloying lithium-ion battery electrode with excellent potential to replace silicon and graphite anodes, offers improved cycle stability and fast-charging capabilities. During the formation cycle(s), SiN x irreversibly converts into a mixture of lithiated silicon and nitridosilicate matrix. However, beyond this basic understanding, there is limited fundamental insight into how the post-conversion structure results in improved electrochemical performance. This significantly hinders the optimization and commercialization prospects of SiN x anodes. Herein, operando electrochemical atomic force microscopy is used to uncover the morphological and chemo-mechanical changes of SiN x thin films during the conversion reaction. We elucidate that the post-conversion SiN x forms silicon domains embedded within a matrix with a core-shell-like structure comprised of a stiff outer nitridosilicate surface and softer inner Si-rich core. The silicon domains that form have very stable dimensions (∼100 nm in diameter) that, crucially, remain smaller than the critical cracking threshold of silicon. This results in a more mechanically robust anode, anticipated to be free from the adverse effects of cracking, pulverization, and subsequent capacity fade. Our work marks an important advance in the fundamental understanding of silicon nitride anodes and offers a pathway to their incorporation into next-generation batteries
Probing amplified Josephson plasmons in YBa 2 Cu 3 O 6+x by multidimensional spectroscopy
Get PDFThe nonlinear driving of collective modes in quantum materials can lead to a number of striking non-equilibrium functional responses, which merit a comprehensive exploration of underlying dynamics. However, the coherent coupling between nonlinearly-driven modes frequently involves multiple mode coordinates at once, and is often difficult to capture by one-dimensional pump probe spectroscopy. One example is phonon-mediated amplification of Josephson plasmons in YBa2Cu3O6+x, a phenomenon likely associated with the mysterious superconducting-like optical response observed in this material. Here, we report two-dimensional nonlinear spectroscopy measurements in driven YBa2Cu3O6+x. We excite apical oxygen phonons with pairs of mutually-delayed carrier envelope phase stable mid-infrared pump pulses, and detect time-modulated second-order nonlinear optical susceptibility. We find that the driven phonons parametrically amplify coherent pairs of fluctuating opposite-momentum Josephson plasma polaritons, corresponding to a squeezed state of the Josephson plasma
The role of Menin in transcriptional regulation of MLL-AF4 and NPM1-mutated leukaemia
Get PDFInhibition of the protein-protein interaction between Menin and Mixed Lineage Leukaemia 1 (MLL, also known as KMT2A) is emerging as a promising targeted treatment for specific high risk acute leukaemias. Menin is essential in leukaemias with rearrangements of the MLL1 gene or mutations in NPM1 — two subtypes with distinct genetic backgrounds. However, the function of Menin in these leukaemias, and why inhibiting its interaction with MLL is effective in these subtypes and not others, remains elusive.
Menin is a scaffold protein which can interact with wild-type MLL, MLL fusion proteins, and with mutant NPM1 (known as NPM1c) to facilitate binding at their gene targets. Rearrangements of MLL1 give rise to oncogenic fusion proteins, most commonly MLL-AF4, which form a multi-protein chromatin complex with Menin, and activate transcription of haematopoietic stem cell genes. On the other hand, mutations in NPM1 cause the encoded chaperone protein nucleophosmin to mislocalise from the nucleolus to the cytoplasm, or to directly bind and activate self-renewal genes in cooperation with Menin and wild-type MLL. Defining how Menin regulates transcription in these two leukemia subtypes, while participating in distinct chromatin complexes, is key to understanding how Menin inhibitors can best benefit leukaemia patients.
In this thesis, I tested the transcriptional response of MLL-AF4 and NPM1c leukemia models to Menin inhibition. Despite a general loss of Menin binding at active regulatory regions in both, and a redistribution of MLL and NPM1c chromatin binding, the transcriptional responses differed. MLL-AF4 cells exhibited rapid, broad transcriptional dysregulation upon Menin inhibition, while NPM1c cells did not have a strong immediate transcriptional response and instead required long-term exposure to alter gene expression. Identifying leukaemia subtype-specific protein- protein interactions by Menin immunoprecipitation followed by mass spectrometry revealed a greater enrichment for components of the transcriptional machinery in MLL-AF4 cells as compared to NPM1c cells. Finally, I demonstrated that Menin specifically regulates enhancer activity and maintains enhancer-promoter contacts in MLL-AF4 cells but not NPM1c cells. Together, these findings point to distinct Menin activity as a more general transcriptional co-activator and regulator of enhancer-promoter proximity in partnership with MLL-AF4 in acute lymphoblastic leukaemia, unique to its regulatory roles in NPM1c acute myeloid leukaemia
Using Abattoir-Based Surveillance to Establish Foot-and-Mouth Disease Non-Structural Protein Seropositivity in Cattle and Pigs in Cambodia
Get PDFFoot-and-mouth disease (FMD) is a contagious transboundary animal disease that causes economic loss and obstacles to international trade. Frequent FMD outbreaks in Cambodia negatively impact farmers’ and smallholders’ incomes. This study aimed to estimate the seroprevalence of FMD Non-Structural Protein (NSP) antibodies, which are an indicator of FMD antibodies raised during a natural infection rather than those produced following vaccination, that were detected using a commercial enzyme-linked immunosorbent assay (ELISA). Sample collection from cattle and pigs (n = 2238) was performed at ten abattoirs in seven provinces between October 2019 and December 2020. Overall seroprevalence in cattle and pigs was 43.2% (363/839; 95% CI 39.8–46.7), and 0.6% (9/1399; 95% CI 0.2–1.2), respectively. Only the cattle dataset was included in the risk factor analysis, as the prevalence of sero-reactors was too low in the pig dataset to be analyzed. Significant risk factors identified by the logistic regression model included the province of origin (p = 0.02), body condition score (BCS) (p = 0.0002) and sex (p = 0.0007). Odds ratios of the significant risk factors were 7.05 (95% CI 1.43–34.67; p = 0.02) for cattle that originated from Kampong Thom, 1.41 (95% CI 1.05–1.89; p = 0.02) for female cattle, and 3.28 (95% CI 1.06–10.12; p = 0.04) for animals with BCS of 3/5. The study revealed that the seroprevalence of FMD NSP in cattle presented at the abattoirs was high, while the FMD NSP seroprevalence in abattoir pigs was very low. Further investigation is required to map the disease distribution in Cambodia, especially the serotypes and strains causing clinical disease. These findings call for the extension of work on effective disease prevention measures
A Review of the Ocular Phenotype and Correlation with Genotype in Poretti-Boltshauser Syndrome
Get PDFBackground and Objectives: Poretti-Boltshauser syndrome (PBS) is a rare, autosomal recessive disorder caused by pathogenic variants in the LAMA1 gene, resulting in laminin dysfunction. This manifests as a cerebellar malformation with cysts, and patients present with developmental delay and ataxia; however, ocular features are not well-characterised. We aimed to summarise the ocular phenotypes of PBS based on cases reported in the literature. Materials and Methods: A literature search was conducted on Medline, Embase, and PubMed on PBS and its ocular associations. Genetically confirmed PBS cases were reviewed, and genotype-phenotype correlations were investigated. Results: Comprehensive reporting of genotypes and associated systemic and ocular phenotypes was available in 51 patients with PBS, who had 52 distinct variants in LAMA1. Most patients carried homozygous variants. The most common genotype was a c.2935delA homozygous mutation, followed by the c.768+1G>A; c.6701delC compound heterozygous mutation. High myopia was the most common ocular phenotype (n = 39), followed by strabismus (n = 27) and ocular motor apraxia (n = 26). A wide range of other ocular manifestations, including retinal dystrophy, retinal neovascularisation, retinal detachment, strabismus, nystagmus, optic disc and iris hypoplasia, were reported. Patients with the same genotype exhibited variable expressivity. Conclusions: PBS has a broad ocular phenotypic spectrum, and characterisation of this variability is important for making an accurate diagnosis and informing genetic counselling
From Inefficient to Efficient Renewable Heating: A Critical Assessment of the EU Renewable Energy Directive
Get PDFThe accounting methodology for renewable energy in the European Union’s (EU) renewable heating and cooling targets is often treated as a mere technical detail, yet it has profound implications for the effectiveness of climate policies. This paper highlights a critical misalignment within the Renewable Energy Directive (RED), which inadvertently disincentivises the deployment of more efficient heating technologies. By accounting for the energy harnessed to produce the useful heat, rather than the useful heat itself, the current metrics disproportionately credit the least efficient heating systems with generating the most renewable heat. An electric heat pump with a seasonal performance factor of 3 producing 100 units of renewable heat gets credited with 100 units of heat, despite using only 33 units of input energy, whereas a wood fireplace with an efficiency of 50% gets credited with 200 units of heat. The less efficient the device, the more renewable credits it receives for producing the same amount of useful heat. This misalignment undermines decarbonisation efforts by over-crediting inefficient technologies while failing to fully recognise high-efficiency solutions like heat pumps. This paper proposes revising the RED to account for useful energy output, ensuring a more accurate reflection of technology contributions. We also propose increasing the binding heating and cooling targets of 0.8 pp/year and 1.1 pp/year so that they reflect the needed contribution of the heating and cooling sector to reach the binding headline target of 42.5% by 2030. This shift would incentivise efficiency, better align with EU climate goals, and support the transition to a low-carbon heating and cooling sector in line with the 2030 emissions reduction target