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Unlocking the Zn-enriching potential of industrial yeast strains—an experimental journey from metal analysis to proteomics
Get PDFNutritional supplements such as trace element-enriched yeasts are becoming increasingly popular to overcome the worldwide problem of zinc (Zn) deficiency. Unlike selenium-enriched yeast, which is already authorized in the European Union, Zn-enriched yeasts (ZnY) have not yet been approved for food purposes in the European Union, as their evaluation is still ongoing, demanding more comprehensive data regarding the Zn species present in ZnY. This study screens ten different industrial yeast strains regarding their Zn-enrichment quota, with further characterization of selected strains using spectroscopic and proteomic approaches. Microfermentation experiments on the industrial yeasts showed Zn levels spanning 0.06–51 pg/cell. Large-scale fermentation in bioreactors was carried out with two strains excelling in either biomass or Zn accumulation. A combination of inductively coupled plasma mass spectrometry (ICP-MS) and various spectroscopic methods confirmed the Zn enrichment, while suggesting that fractions of the Zn accumulated on the cell surface, with simultaneously high values of phosphorus being present. Speciation via X-ray absorption spectroscopy (XAS) analyses revealed that Zn species are transformed and Zn is coordinated to P-O-ligands and to amino acid ligands in both strains. Proteomic analysis showed that ZnY cells moved from a Zap1-governed Zn balance to an intracellular excess response, implying cellular Zn uptake. This study demonstrates that, in a Zn-excess medium, industrial yeast strains exhibit variability in Zn-accumulation capacity, cellular Zn-localization, and regulatory responses involving the expression of Zn-binding proteins. The presented findings contribute to optimizing industrial fermentation processes for producing Zn-rich yeast biomass and enhance the understanding of Zn regulation in yeast, aiding in the approval of Zn-enriched yeasts for supplements and novel food applications. Key points: • Zn enrichment in yeasts is strongly time and strain dependent • Zn proteome changes under Zn excess suggest that Zn is partly internalized in the yeast cells • Beside proteins, phosphorous compounds seem to be Zn-binding ligands in Zn-enriched yeas
How machine learning models encode knowledge – and what we can learn from them
Get PDFAs machine learning systems become increasingly capable--often surpassing human performance--they present both a challenge and an opportunity for understanding. These complex systems may operate in ways that are distinct from human reasoning, making them difficult to interpret. Yet, they also hold the potential to reveal new knowledge and support critical decisions in domains such as healthcare, science, and education.
This thesis examines interpretability as a means of understanding and learning from machine learning models. We focus on two central goals: (1) to understand what and how knowledge is encoded in machine learning models and (2) to extract that knowledge in a form that is meaningful and accessible to humans. To this end, we propose a structured pipeline with four stages: identifying explanation desiderata, locating encoded knowledge or concepts, verifying that the concepts influence model behaviour, and translating the concepts into a human-interpretable form. Within this framework, we adapt existing methods where appropriate and develop new ones where necessary--selecting the approach best suited to the task. Our focus is not only on methodological development but also on understanding how these methods behave and the assumptions they make.
Different parts of the thesis contribute to each stage of this pipeline. We begin by investigating how models encode knowledge: first, by analysing the linear representation hypothesis and then examining the universality of concept representations in multilingual language models. We then shift to the user-facing side of interpretability. We study how to make explanations more user-friendly by leveraging uncertainty to generate realistic and unambiguous explanations. Finally, we apply the full pipeline to develop a framework for extracting novel concepts from AlphaZero and teaching them to chess experts. This final study illustrates how interpretability can help bridge the gap between artificial and human understanding. Together, these contributions advance our understanding of and ability to learn from machine learning systems, laying the groundwork for future research at the intersection of artificial intelligence and human insight
The Port Harcourt Question: the meaning of land in a city in south-eastern Nigeria
Get PDFThis thesis, based on a year of ethnographic research in Nigeria, revolves around a land conflict between two ethnic groups who contest ownership of Port Harcourt, a city in the southeast of the nation. The two ethnic groups are the Ikwerre and the Okrika. The Ikwerre and the Okrika are very different peoples with their own histories and livelihoods: the former being sedentary yam farmers, the latter seminomadic fisherfolk and, in earlier times, slave traders. I contrast their understandings of land. I go on to examine the way the city and their conflict over its land have brought these different understandings together.
The Port Harcourt Question—who owns Port Harcourt?—is the name inhabitants of the city give to the long-standing land dispute between the Ikwerre and the Okrika. The purpose of this thesis is principally to explore this question. It is not, however, an attempt to answer the question. Rather I seek to understand the genesis of the question and why it continues to be asked. To do this I ask and answer three other questions which are formed by inserting two additional question marks into the Port Harcourt Question thus: (i) Who? (ii) Owns? (iii) Port Harcourt?
In addressing the first of these questions (Who?), I describe the Ikwerre and the Okrika and how they gain and transmit land rights. Understanding how land rights are gained and transmitted is necessary to make sense of how land disputes in the city play out.
In addressing the second question (Owns?), the verb of the Port Harcourt Question, I speak to scholarship, anthropological and otherwise, on ownership and property. I examine what ‘owning’ land means in this context and why it is so contentious. I also explore what land means and how this entity differs from other things which are said to be ‘owned’. Particular attention is given to the law— litigation being the chief way the land disputes between the Ikwerre and the Okrika play out.
The third question (Port Harcourt?) challenges the received understanding of Port Harcourt as a non-traditional city of strangers created ex nihilo by Europeans. I argue that the city owes its contemporary form to its pre-urban history, a history which, given the notion that the city emerged from virgin swampland, is assumed not to exist.
Ultimately, I argue that it is history which perpetuates the Port Harcourt Question. Historical knowledge gives substance to the claims made by the Ikwerre and the Okrika to own the land of the city. I contend that, in this context, the historical knowledge which underlies claims to ownership is potential
The Soil Erosion Paradox Re‐Examined: Alluviation and Land Use History in a Small British Lowland River Catchment in the Late Holocene
Get PDFModern studies show that soil erosion results in a loss of ecosystem function, particularly fertility, and is a cause of declining agricultural yields. However, despite the well‐attested high rates of soil erosion across Roman and medieval Europe there appears to have been little or no soil‐associated decline in agricultural production—the soil erosion paradox. Small low‐slope erodible lowland catchments offer the opportunity to examine this question when sufficient historical information is available. Here, we show that, since its disconnection from the main River Severn (UK) floodplain in the mid‐Holocene, the small Hatfield Brook catchment experienced high rates of soil erosion and alluviation (~2 mm year−1) associated with extensive catchment‐bound open‐field system agrarianism. Scientific and historical data both indicate increases in activity during the early medieval and medieval periods, associated with landscape control by the Bishopric of Worcester (BoW). Agricultural expansion by the church from the late 11th to mid‐13th centuries ad extended further into lower valley slopes and alluviated flatlands, tilled using the heavy plough, and catchment hinterlands were further cleared of woodland via assarting, all leading to greater soil erosion. After ad 1250, the power and influence of the Bishopric of Worcester declined with arable cultivation and a move towards pastoralism leading to a reduction in soil erosion, increased slope stability and floodplain deposition. This suggests that in the low‐relief erodible lowlands of Europe one solution to the erosion paradox is that most of the sediment generated by open‐field cultivation was trapped in the basin and created new, flat, and highly productive agricultural land producing both a sustainable farming system and a non‐linearity in the relationship between population and soil erosion. Further modelling‐based research is needed though to identify the relative role of the manipulation of fertility through manuring and new land‐creation
Beyond Normativity
Get PDFRecent years have seen a growing number of philosophers come to defend normative nihilism. Even if their arguments do not induce in many a belief in normative nihilism, there may be grounds on which to be less than certain about the falsity of normative nihilism. How, then, can we accommodate the possibility of normative nihilism when deliberating about what to do? In this article, I defend two theses. First, I distinguish between normative questions and deliberative questions and argue that the question “what am I to do under uncertainty about the truth of normative nihilism?” is best understood as an example of the latter. Second, I propose a novel framework for deliberation under uncertainty about the truth of normative nihilism: maximize expected decision‐relevance. A striking upshot of this article is that there is an important sense in which we need make no mistake by flouting normative considerations under uncertainty about the truth of normative nihilism
Desegregating spaces: the interplay between ecological intergroup contact and GPS-traced spatial segregation among youth in two UK cities
Get PDFRecent advances in intergroup contact research have drawn on methods from human geography to investigate how segregation shapes, and is shaped by, everyday intergroup experiences. Emerging findings suggest that the phenomena might be reciprocally intertwined, but empirical evidence is limited and mixed. This research tested the reciprocal relationship between everyday intergroup contact and segregation using ecological momentary assessment and GPS-GIS tracking in two segregated UK cities with youth aged 15–17. Study 1 (Belfast; nparticipants=15; ninteractions=115; nGPS-point=633) focused on Catholics-Protestants divisions, and Study 2 (Bradford; nparticipants=30; ninteractions=334; nGPS-point=2868) addressed ethnic segregation among Asian, White, and Black communities. In both studies, youths reported on social interactions throughout six days, while their urban mobility in outgroup spaces was tracked. In Belfast, more mixed districts predicted higher anxiety during intergroup interactions, yet positive intergroup contact was followed by increased visits to outgroup spaces. In Bradford, mixed districts increased the likelihood (but not the quality) of intergroup contact, while the link between positive contact and subsequent outgroup space use was replicated. The findings highlight a virtuous cycle depending on contextual norms by which positive contact and desegregation practices might reinforce each other, arguably demonstrating the potential of intergroup contact for levelling urban divisions
Boundary spike-layer solutions of the singular Keller-Segel system: existence, profiles and stability
Get PDFThis paper investigates boundary-layer solutions of the singular Keller-Segel system (proposed in [19]) in multi-dimensional domains, which describes cells’ chemotactic movement toward the concentration gradient of the nutrient they consume, subject to a zero-flux boundary condition for the cell density and a Dirichlet boundary condition for the nutrient. The steady-state problem of the system reduces to a scalar nonlocal Dirichlet elliptic problem with a singularity. By analyzing this nonlocal problem, we establish the existence of a unique steady-state solution which forms a boundary spike-layer profile as the nutrient diffusion coefficient ε → 0. For radially symmetric domains, we derive explicit expansions for the boundary-layer steepness and thickness in terms of the domain radius (for small ε > 0), which quantifies the influence of radius on the profile and thickness. Additionally, we prove the nonlinear exponential stability of this boundary-layer steady-state in radially symmetric domains. The key challenge in our analysis is the emergence of a singularity for small ε in both stationary and time-dependent problems. To address this, we reduce the nonlocal steady-state problem to a local one and conduct a refined analysis via the barrier method and Fermi coordinates, yielding sharp estimates for the local steady-state solution near the boundary. This approach enables us to determine the asymptotic profile of the nonlocal problem’s solution as ε → 0, accurately capturing and properly resolving the singularity to establish our main results. For the time-dependent problem in radially symmetric domains, we employ a variable transformation to eliminate the singularity, ultimately proving the nonlinear stability of the unique steady-state solution. Our analysis leverages the equation governing the radial mass distribution function relative to the steady state, along with delicate time-weighted energy estimates
Punishment, state, and society in the global periphery: Mass incarceration, mass incorporation, and the rise of a protagonist Judiciary in Brazil
No full textThis thesis explains the production and reproduction of mass incarceration in Brazil, the country with the world’s third-largest prison population. It challenges dominant Global North theories—such as penal populism and neoliberal penality—by analysing how mass incarceration has emerged and persisted in a peripheral, dependent state undergoing democratisation, economic growth, and social inclusion. This thesis argues that it results from two processes that intersect: the expansion of the state and the rise of a protagonist judiciary, both operating within historically specific, structurally unequal conditions. The first process traces how Brazil shifted from domestic, informal and hidden forms of punishment—prevalent in slaveholding, rural, and authoritarian periods—to official state punishment. This transformation reflects deeper changes in social control, tied to the incorporation of previously marginalised populations into state governance and control. The second process examines the central role of the judiciary in sustaining and intensifying mass incarceration. Judges were empowered and the judiciary expanded during the democratic transition, but left institutionally unreformed, thereby becoming a key actor in the penal state. Its recruitment filters—bureaucratic and class-based—reproduced a judicial class largely aligned with a punitive consensus. Those who somehow overcome these filters, without consensually adhering to the punitive normality, face institutional coercion through reassignment, disciplinary measures, and criminalisation, with the result that dissent judges are neutralised and institutional conformity ensured. Methodologically, the thesis combines sociohistorical analysis, court-file analysis, in-depth interviews, and online observation. Theoretically, it draws on Southern Criminology, Critical Realism, the political economy of punishment and agonistic perspectives to develop a historically grounded, empirically rich account of mass incarceration in Brazil. It ultimately shows how mass incarceration was not a deviation from democratic consolidation, but a constitutive element of it, shaped by the very ways state power, judicial roles, and class domination were reconfigured in post-authoritarian Brazil
Pelagic marine ecosystem responses to late Pleistocene climate change
Get PDFPelagic marine ecosystems occupy the most expansive habitat on the Earth and influence global climate through the organic carbon pump. In this thesis I tested for changes in North Atlantic primary, fish, and export production using two sediment cores – subpolar ODP Hole 982B and midlatitude IODP Hole U1313A – during late Pleistocene glacial-interglacial cycles in the past 200 kyrs. I hypothesised that there were causative changes in ecosystem production at different trophic levels driven by climate change, including long-term oceanographic and water temperature changes.Coccolithophores are an ecologically important clade of eukaryotic phytoplankton in the modern pelagic ocean. I reconstructed the accumulation rate and demography of coccoliths and found significantly higher subpolar coccolith accumulation during interglacial intervals relative to glacial intervals. This was likely due to the importance of North Atlantic Transitional Waters (NATW) in sustaining warm and relatively eutrophic conditions favourable to coccolithophore proliferation during interglacial intervals. In contrast, there was no significant glacial-interglacial change in coccolith accumulation or taxonomy at the midlatitude site, which I attribute to the persistent presence of NATW.Excess barium (BaXS), a proxy for organic carbon export, increased rapidly in the subpolar North Atlantic during the past two deglaciations. In the midlatitude ocean, BaXS was strongly correlated with glaciogenic and aeolian detrital input proxies. High latitude export may have been limited by enhanced glacial stratification, but basin-scale export was likely enhanced by allogenic nutrient-driven increases in the midlatitude ocean, which coincided with greater continental aridity and ice rafting. These findings imply that the midlatitude North Atlantic could have been a hitherto unrecognised region of enhanced biogenic carbon sequestration during past glacial intervals, contributing to the drawdown of atmospheric carbon dioxide.Ichthyoliths, microfossil fish remains, record the abundance and composition of mesopelagic fish fauna. Interglacial ichthyolith accumulation rate (IAR) was higher than glacial IAR at both sites but showed little relationship to proxy reconstructions of primary production. This suggests that mesopelagic fish production was strongly influenced by temperature-induced changes in trophic transfer efficiency on multi-millennium timescales. If this trend was sustained, mesopelagic fish abundances could respond positively to long-term future ocean warming, contrary to what is predicted by most marine ecosystem models. IODP Site U1313 had by far the highest mean IAR of any site where IAR has been constructed to-date. This result suggests either that the midlatitude Pleistocene North Atlantic was far more productive for mesopelagic fishes than these other pelagic locations, or that the IAR proxy imperfectly captures fish productivity in this setting. This work highlights the Pleistocene North Atlantic as a promising region for future ichthyolith research.Linear regressions of the three productivity proxies suggest that coccolithophore production was positively related to organic carbon export in the midlatitude North Atlantic during the Last Interglacial and during glacial intervals in the subpolar ocean, indicating the importance of coccolith biomass to export in oligotrophic conditions. Future anthropogenic climate change will cause substantial changes to ocean ecosystems. The late Pleistocene provides examples of ecosystem responses to major oceanographic perturbations in the recent geological past, which may prove useful analogues for near-future change.This thesis evidences the utility of palaeontological and geochemical approaches to reconstructing biological responses to past climate change. Glacial-interglacial climates were marked by distinct changes in coccolithophore, fish, and export production in the North Atlantic. Coccolithophore production responded most strongly to changes in the position of NATW, export production was strongly influenced by allogenic nutrient inputs, and mesopelagic fish production showed a positive relationship with ocean temperature. Whilst these methods have limitations, such as capturing only a fraction of total production, they can provide an empirical means of informing future climate change scenarios
Decadent Webster: Swinburne, Symonds and the poet of 'dreadful stuff'
No full textAccording to John Addington Symonds’s introduction for the Mermaid Series edition of the plays of John Webster and Cyril Tourneur (1888), Webster excelled at depicting the ‘dreadful depths in human nature’. The fin de siècle fascination with humanity’s ‘dreadful depths’ is well-known, and the word ‘dreadful’ has long been synonymous with the late Victorian urban concoction of sexual delight and danger. What Symonds terms the ‘dreadful stuff’ of Webster’s tragedies The White Devil (1612) and The Duchess of Malfi (1614) derived from the criminal history of the Italian Renaissance, of which Symonds was the pre-eminent nineteenth-century historian. Symonds and the leading Victorian critic of Elizabethan drama, Algernon Charles Swinburne, both took Webster as the subject of their earliest dramatic criticism and returned frequently to the ‘dreadful stuff’ of these two plays. This article traces the roots and implications of that preoccupation, arguing that the ‘dreadful stuff’ of Webster’s Italian tragedies was integral to these writers’ sexual as well as critical psychologies. For Swinburne, the suffering of Webster’s Duchess presented a study in the connoisseurship of pain and the power of erotic pathos, while for Symonds the gender-ambiguous ‘dreadful daring’ of Vittoria Accoramboni in the trial scene of The White Devil was rapturously arousing. The article underscores the importance of Webster’s tragedies in creating a space in the late nineteenth century for critical and erotic speculations about art, pain and desire