The early evolution of small terrestrial bodies: a palaeomagnetic and geochemical study of meteorites

Meteorites act as windows into the early solar system, providing a wealth of information on the composition, formation, and evolution of planetary bodies. After their formation, planetary bodies are reworked by several secondary processes which modify their original chemical and physical properties. In this thesis, I study two such processes (aqueous alteration and impacts), using magnetic and geochemical techniques on stony-iron, iron, and chondritic meteorites. The formation of stony-iron meteorites is a topic of intense research and both mesosiderites and pallasites are hypothesised to have formed through impact mixing of metal and silicates. I use palaeomagnetic and microscopy techniques on the mesosiderite Estherville and show that Estherville does not record a high-coercivity natural remanence. However, Estherville has the ability to record strong (>150 μT) fields. The slow cooling rates recorded by mesosiderites (<1 K/Myr) imply a formation close to the core-mantle boundary, suggesting that they would have been exposed to strong fields if a dynamo was active. However, they do not carry a high coercivity remanence, which may indicate that the mesosiderite-forming impact shut off the dynamo. To investigate the formation of pallasites, I use in situ chemical analysis and find that all metal in Seymchan has the same origin. Based on this result and textural observations, I propose a pallasite formation model involving two or more impacts, and provide additional evidence for the previously proposed link between Main Group pallasites and IIIAB meteorites. Finally, I study aqueous alteration using quantum diamond microscope magnetic mapping to spatially resolve the magnetic signals of the CM chondrite MCY 05231. I suggest that magnetite forms via different reaction pathways in this sample, and that magnetite formed via pseudomorphic replacement of metal leads to the inheritance of magnetic remanence from the precursor grain. I use these results to suggest a magnetic history for MCY 05231, and to discuss implications for bulk magnetic studies of chondrites

Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of bla KPC -carbapenemase-producing Enterobacterales in a hospital setting

Background: Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear. Methods: We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6–12 months to understand blaKPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs. Results: Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P < 0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath- and sluice/mop-associated sites were more likely to be KPC-E-positive (adjusted OR = 2.69; 95% CI: 1.44–5.01; P = 0.0019; and adjusted OR = 2.60; 95% CI: 1.04–6.52; P = 0.0410, respectively). Different strains had different blaKPC dissemination dynamics. Conclusions: We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies

Can the UK achieve net-zero greenhouse gas emissions by 2050?

Net-zero greenhouse gas emissions by 2050, the UK’s current target, requires bridging a dramatic energy transition and eliminating all other net sources of emissions while ensuring a just transition. Key components like renewable electricity generation and electric vehicles are well developed, but many issues remain. Public support for a green economy may wane if the economic costs are too high or seen as unfair, so although renewable energy is cheaper than fossil fuels, it is essential to maintain employment, real per-capita growth and reduced inequality. Decarbonizing the UK economy requires an integrated sequential approach and need not be delayed while dealing with the aftermath of the Covid-19 pandemic, energy crisis and resulting inflation

Sor Juana Inés de la Cruz, Critique of a Sermon and Other Letters: Crisis sobre un sermón, Carta de sor Filotea (by Manuel Fernández de Santa Cruz), Respuesta a sor Filotea

Sor Juana’s Respuesta a sor Filotea (1691) is one of her most widely read works and an established text in the history of women’s writing. Less frequently studied is the epistolary exchange to which it responds, particularly Juana’s Crisis sobre un sermón (or Carta atenagórica, 1690), her response to a sermon by the Portuguese Jesuit Antonio Vieira on Christ’s greatest fineza, or demonstration of love. In the Crisis, Sor Juana puts into practice what she would later argue in the Respuesta: that women could, and should, engage in theological study, and that a woman’s well-reasoned argument would defeat any man’s ill-founded and unorthodox thought. This is the first annotated, critical edition and English translation of the complete published exchange between Sor Juana and Manuel Fernández de Santa Cruz, with a comprehensive introduction, commented textual variants, and extensive textual notes. The introduction explores how the Crisis can be read in relation to Juana’s other works, including her love poetry, her eucharistic drama El mártir del Sacramento, and Primero sueño. By analysing its central themes, this study argues that the Crisis is key to Juana’s defence of women’s learning, while also shedding light on her views on gender, theological enquiry, and the dynamics of love, both religious and secular

Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal–fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genes HAND2, TBX3 and RAP2C/FRMD7 at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified

Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of blaKPC-carbapenemase-producing Enterobacterales in a hospital setting

Background Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear. Methods We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6–12 months to understand blaKPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs. Results Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P KPC dissemination dynamics. Conclusions We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies

The enhanced wave-induced drift of large floating objects

At the ocean surface, mass, momentum and energy are transferred between the atmosphere and the ocean. Ocean surface waves, in particular, drive the transport of floating objects such as sediments, pollutants, and man-made structures. In irrotational and progressive surface gravity waves, water particles exhibit a non-closed path over one wave cycle, leading to Stokes drift. The drift can be modified, and indeed enhanced, when an object deviates from being an ideal Lagrangian tracer. This thesis examines the wave-induced drift of two-dimensional (2D) floating objects by surface gravity waves, specifically, deep-water regular waves. A combination of analytical, numerical, and experimental approaches are employed to analyze the drift of objects with varying sizes and shapes under different wave steepness. A hybrid numerical model encompassing both viscosity and diffraction effects is used to investigate the influence of changing size, shape and wave steepness on the object drift. The drift deviates from the standard Stokes drift and depends on objects’ size and shape. Larger objects with less streamlined shapes, resembling box-like structures, exhibit enhanced drift. The enhancement is attributed to the standing wave pattern generated as a result of diffraction of the wave field, and viscosity. A diffraction-modified Stokes drift model is proposed to predict object drift. The model introduces additional terms to the standard Stokes drift, accommodating incident, diffracted, and radiated wave fields. The results are compared to both experimental measurements and numerical results, demonstrating a close agreement when the object is not too large. The model offers an in-depth understanding of one of the mechanisms contributing to drift enhancement. A 2D experiment has been conducted in a laboratory flume. The floating objects are specially designed to ensure the experiment is two dimensional. The enhanced drift, along with the associated standing wave pattern, predicted by the model is also observed in experimental data, which validates the theoretically predicted enhanced drift. Distinct drift behaviours are identified for small and large objects at low and high wave steepness. The data reveals that the scaling relationship between the object drift and steepness is characterized by a mixture of linear and second-order terms (in steepness) and is dependent on object size. The influence of object corner shape on drift is further explored using the hybrid numerical model. In particular, the drift of a bluff body with sharp and round corners has been investigated. It is found that an object’s sharp corners can induce vorticity and thus change the pressure distribution around the moving objects, resulting in a significantly altered drift trajectory and unsteadiness in the object’s drift

Covalent penicillin-protein conjugates elicit anti-drug antibodies that are clonally and functionally restricted

Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates and their off-target side-conjugates have the potential to elicit antibodies, with implications for allergy and drug sequestration. Although β-lactam antibiotics are a drug class long associated with these immunological phenomena, the molecular underpinnings of off-target drug-protein conjugation and consequent drug-specific immune responses remain incomplete. Here, using the classical β-lactam penicillin G (PenG), we probe the B and T cell determinants of drug-specific IgG responses to such conjugates in mice. Deep B cell clonotyping reveals a dominant murine clonal antibody class encompassing phylogenetically-related IGHV1, IGHV5 and IGHV10 subgroup gene segments. Protein NMR and x-ray structural analyses reveal that these drive structurally convergent binding modes in adduct-specific antibody clones. Their common primary recognition mechanisms of the penicillin side-chain moiety (phenylacetamide in PenG)—regardless of CDRH3 length—limits cross-reactivity against other β-lactam antibiotics. This immunogenetics-guided discovery of the limited binding solutions available to antibodies against side products of an archetypal covalent inhibitor now suggests future potential strategies for the ‘germline-guided reverse engineering’ of such drugs away from unwanted immune responses

Modelling tool extension for vulnerability management

Managing vulnerabilities with respect to the design of systems is essential to securing systems and establishing their trustworthiness. Until now, there has been no modelling tool to support vulnerability management within the context of system design. We present a new, open-source extension of a systems security design and assessment tool. First and foremost, this extension integrates pertinent vulnerability management domain ontology into the tool’s underlying metamodel. Based on the extended metamodel, the enriched tool supports importing information from vulnerability-related knowledge bases as well as capturing new vulnerability information and security rules. This information can then be used in an integrative and scalable form to analyse and reason about the security of systems designs. The extended tool now includes an automated reasoning mechanism for establishing the vulnerability posture of systems designs