143174 research outputs found
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Bitcoin in the post-quantum era: preparing the transition of utxo-based blockchains to quantum resistance
No full textThis dissertation explores the impact of quantum computing on UTXO-based blockchains like Bitcoin, presenting two significant contributions to the field. The primary contribution introduces two novel cryptographic schemes designed to securely transition from current cryptographic mechanisms to quantum-resistant alternatives. These schemes focus exclusively on the signature verification process, ensuring compatibility with all transaction types, including multi-signature transactions.
The first scheme is highly efficient, requiring minimal changes to Bitcoin’s codebase—fewer than 100 lines in the proof-of-concept implementation. The second scheme, while more complex, incorporates symmetric encryption and decryption algorithms. This allows users to customize security parameters based on their risk perception and asset value, providing a flexible transition strategy.
The secondary contribution involves an empirical analysis of the financial risks posed by quantum-capable adversaries. This dissertation evaluates how advancements in quantum computing could compromise the cryptographic foundations of blockchains and quantifies the potential for value extraction by quantum attackers under existing security frameworks.
In summary, this research identifies and quantifies the risks introduced by quantum advancements and proactively proposes strategic approaches to fortify decentralized blockchain systems in preparation for the quantum era. By addressing both the technical transition to quantum-resistant cryptography and the associated financial risks, the dissertation offers a comprehensive framework for enhancing the security and resilience of UTXO-based blockchains against future quantum threats.Open Acces
A uv-pump x-ray-probe beamline developed for high time resolution measurement and control of photochemical reactions
No full textOver the last 40 years, ultrafast laser spectroscopy has allowed the transient nuclear dynamics of a vast range of photochemical reactions to be observed. However, study of the first few fs electronic dynamics remains out of reach. Much ground has been covered with the creation of attosecond x-ray pulses from high harmonic generation (HHG) and x-ray free electron lasers (XFELs), however the challenge remains with the observation of valence electronic dynamics on the same few-femtosecond timescale. Many of the iconic reactions such as the ring opening of small molecules, photosynthesis, light harvesting in solar cells and vision occur on this timescale. Here, a beamline capable of capturing electronic dynamics is presented. This is achieved by developing pump pulses from resonant dispersive wave (RDW) emission in hollow core waveguides. This is proved capable of producing sub-5 fs pulses continuously tuneable from the deep ultraviolet to the visible. This is combined with isolated attosecond probe pulses from HHG which can measure atomic specific dynamics at energies beyond the C K edge. These two pulses constitute a spectroscopic technique with which valence dynamics can be measured with unprecedented temporal resolution. How the flux and cut-off of the high harmonics have been improved is reported, along with the absorption measurements at several atomic edges. The development of the RDW emission is reported, including its tuneability, pulse energies, delivery method, and pulse durations. The impressive sub-fs stability between each arm is reported. The ability to deliver targets in gas/vapour, solid and liquid/solution phase is presented. Proof of this technique's ability to measure ultrafast photochemical dynamics is given with the x-ray absorption spectroscopy of the photofragmentation of dimethyl disulphide (DMDS). Future plans for this experimental technique include studying the fast ring opening of cyclohexadiene and thiophene with an order of magnitude better resolution than previously reported.Open Acces
Membrane remodelling mediated by a cyanobacterial dynamin-like protein
No full textMembrane remodelling is fundamental to cellular life, essential for processes ranging from cell division to organelle maintenance. While lipid bilayers are the predominant membrane structure, non-bilayer lipids and phases play crucial roles in cellular function and stress responses. Proteins are key mediators of membrane remodelling, with the dynamin superfamily representing an ancient and conserved class of membrane remodelling GTPases found across all domains of life. Most eukaryotic dynamins and dynamin-related proteins have defined roles in fission or fusion, such as the mitofusins mediating outer mitochondrial membrane fusion. Bacterial dynamins generally have more diverse cellular roles, but often share conserved characteristics with eukaryotic dynamins, including their domain architecture and ability to self-assemble into helical polymers that constrict lipid membranes. Bacterial dynamin-like protein (BDLP) from the cyanobacterium Nostoc punctiforme serves as a valuable model for investigating bacterial dynamin function and the fundamental membrane remodelling principles of the dynamin superfamily, especially given its homology to the mitofusins. This thesis demonstrates BDLP's specific upregulation during development of motile N. punctiforme filaments, and its putative association with thylakoid membranes remodelled into non-bilayer phases. High-resolution cryo-electron microscopy structures of GMPPNP- and GDP-bound BDLP filaments provide a structural basis of GTP coordination and
catalysis, and demonstrate a novel mechanism of membrane constriction. Cryo-electron tomography reveals how BDLP remodels lipids from a bilayer configuration into a non-bilayer arrangement in vitro, providing the first evidence of a dynamin family member mediating stable lipid phase transitions. These findings expand our understanding of bacterial DRP functions while demonstrating conserved DSF membrane remodelling principles. The identification of a conserved membrane displacement domain across mitofusin-like DRPs suggests a shared mechanism for bilayer disruption, potentially elucidating mitofusin-mediated fusion.Open Acces
Global, regional, and national burden of household air pollution, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBackground
Despite a substantial reduction in the use of solid fuels for cooking worldwide, exposure to household air pollution (HAP) remains a leading global risk factor, contributing considerably to the burden of disease. We present a comprehensive analysis of spatial patterns and temporal trends in exposure and attributable disease from 1990 to 2021, featuring substantial methodological updates compared with previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study, including improved exposure estimations accounting for specific fuel types.
Methods
We estimated HAP exposure and trends and attributable burden for cataract, chronic obstructive pulmonary disease, ischaemic heart disease, lower respiratory infections, tracheal cancer, bronchus cancer, lung cancer, stroke, type 2 diabetes, and causes mediated via adverse reproductive outcomes for 204 countries and territories from 1990 to 2021. We first estimated the mean fuel type-specific concentrations (in μg/m3) of fine particulate matter (PM2·5) pollution to which individuals using solid fuels for cooking were exposed, categorised by fuel type, location, year, age, and sex. Using a systematic review of the epidemiological literature and a newly developed meta-regression tool (meta-regression: Bayesian, regularised, trimmed), we derived disease-specific, non-parametric exposure–response curves to estimate relative risk as a function of PM2·5 concentration. We combined our exposure estimates and relative risks to estimate population attributable fractions and attributable burden for each cause by sex, age, location, and year.
Findings
In 2021, 2·67 billion (95% uncertainty interval [UI] 2·63–2·71) people, 33·8% (95% UI 33·2–34·3) of the global population, were exposed to HAP from all sources at a mean concentration of 84·2 μg/m3. Although these figures show a notable reduction in the percentage of the global population exposed in 1990 (56·7%, 56·4–57·1), in absolute terms, there has been only a decline of 0·35 billion (10%) from the 3·02 billion people exposed to HAP in 1990. In 2021, 111 million (95% UI 75·1–164) global disability-adjusted life-years (DALYs) were attributable to HAP, accounting for 3·9% (95% UI 2·6–5·7) of all DALYs. The rate of global, HAP-attributable DALYs in 2021 was 1500·3 (95% UI 1028·4–2195·6) age-standardised DALYs per 100 000 population, a decline of 63·8% since 1990, when HAP-attributable DALYs comprised 4147·7 (3101·4–5104·6) age-standardised DALYs per 100 000 population. HAP-attributable burden remained highest in sub-Saharan Africa and south Asia, with 4044·1 (3103·4–5219·7) and 3213·5 (2165·4–4409·4) age-standardised DALYs per 100 000 population, respectively. The rate of HAP-attributable DALYs was higher for males (1530·5, 1023·4–2263·6) than for females (1318·5, 866·1–1977·2). Approximately one-third of the HAP-attributable burden (518·1, 410·1–641·7) was mediated via short gestation and low birthweight. Decomposition of trends and drivers behind changes in the HAP-attributable burden highlighted that declines in exposures were counteracted by population growth in most regions of the world, especially sub-Saharan Africa.
Interpretation
Although the burden attributable to HAP has decreased considerably, HAP remains a substantial risk factor, especially in sub-Saharan Africa and south Asia. Our comprehensive estimates of HAP exposure and attributable burden offer a robust and reliable resource for health policy makers and practitioners to precisely target and tailor health interventions. Given the persistent and substantial impact of HAP in many regions and countries, it is imperative to accelerate efforts to transition under-resourced communities to cleaner household energy sources. Such initiatives are crucial for mitigating health risks and promoting sustainable development, ultimately improving the quality of life and health outcomes for millions of people.
Funding
Bill & Melinda Gates Foundation
Real projective groups are formal
No full textWe prove that the mod 2 cohomology algebras of real projective groups are intrinsically formal. As a consequence we derive the Hopkins–Wickelgren formality and the strong Massey vanishing conjecture for a large class of fields
Integrate-and-fire models of financial markets
No full textThis thesis introduces a novel theoretical and computational framework that bridges concepts from physics, complexity science, neuroscience, and behavioural economics to describe financial market dynamics using an integrate-and-fire paradigm. Motivated by the limitations inherent in classical economic theories - especially the efficient market hypothesis and the oversimplification of homogeneous, representative agents- the work explicitly models financial markets as emergent phenomena resulting from the interactions of heterogeneous agents. Traders in this framework integrate information, including market signals and social influences, and decide when decision thresholds are reached, analogous to neuronal firing events.
Through computational modelling and systematic analysis, the thesis reveals several significant findings. It demonstrates that neuronal-inspired decision mechanisms, such as inhibition and information decay (reflecting irrationality and limited memory), are critical for replicating widely observed financial phenomena, including speculative bubbles, sudden market crashes, fat-tailed return distributions, and volatility clustering. Further investigations establish clear relationships between hierarchical information structures (information silos), and mispricing, highlighting how network topology profoundly influences market stability and price dynamics.
Expanding beyond purely financial applications, the thesis generalises the integrate-and-fire framework into a versatile approach capable of describing broader social dynamics. With this approach, we manage to reproduce wealth distributions of traders in financial markets. Remarkably, this generalised framework also successfully captures complex epidemiological patterns, accurately reproducing real-world data from infectious disease outbreaks, including the COVID-19 pandemic, and capturing features such as secondary infection peaks and intervention effects.
Overall, the results underscore the importance of micro-level heterogeneity and network topology in generating complex, non-equilibrium market phenomena, providing new insights into the interplay between individual decision-making and aggregate market behaviour.Open Acces
Age, climate and economic disparities drive the current state of global dam safety
No full textDams are essential for flood protection, water resources management, energy generation and storage and food production. However, the consequences of their failure can be catastrophic, as demonstrated by recent examples. Here this study revisits dam failures worldwide since 1900, analysing key factors driving the failure risk, profiling current dam safety and providing an outlook to the near future. Similar to previous analyses (1970s to 2010s), we observe a strong infant mortality, which remains especially important for the development of new embankment dams, while recent concrete dams have become more resilient. In contrast, hazard signals related to ageing remain yet less apparent, contrary to common belief. Nevertheless, given their abundance, we expect decades-old dams to be prevalent in future failure statistics—especially for embankment dams of height between 15 and 70 m built in the second half of the last century. This highlights the relevance of investments in monitoring, maintenance and uprating, which, if ignored, could become a substantial liability and a major vulnerability, especially in the context of increased flooding frequency. We uncover a trend of increased failure rates of newly constructed dams in low-income regions, which coincides with areas where a substantial hydropower potential remains untapped. This is especially intensified in monsoon-dominated climates, whereas the pattern of construction and failures is more homogeneous across other major climatic regions. Our statistical analysis suggests that 23 (95% confidence interval 14–33) large dam failures are to be expected worldwide in the near future (2023–2035), with currently ~4.4% of large dams having a probability of failure larger than 1/10,000. Contrarily, 85% of large dams are at least twice as safe as this threshold, commonly embraced in policy. These findings can support the targeted allocation of limited resources for the future-proofing of infrastructure, thereby contributing to water, food and energy security
Improving outcomes in abdominal aortic aneurysm patients
No full textBackground
Patients undergoing abdominal aortic aneurysm repair suffer from multiple comorbidities and frailty. Perioperative and postoperative complications are common following AAA repair, and research should be undertaken to improve overall outcomes. Preoperative exercise therapy (Prehabilitation) is a well-described method for improving surgical outcomes; however, it is uncertain if patients scheduled for AAA repair would benefit from prehabilitation. The goal of this thesis is to provide new evidence for prehabilitation in AAA patients awaiting surgery and explore the feasibility of using a novel adjunct to facilitate rehabilitation following surgery.
Methods
This thesis is mainly made up of three main studies. Analysis of National Vascular Registry data to highlight the impact of frailty on patients undergoing AAA repair. A proof-of-concept feasibility study assessing a novel 6-week remote prehabilitation programme for patients scheduled for AAA repair. A pilot randomised controlled study aimed at improving rehabilitation of general and vascular surgery patients using a neuromuscular electrical stimulation device.
Results
The first study highlighted the negative impact of frailty status on short-term outcomes following AAA repair, with a significantly increased risk of combined cardiovascular and mortality events in patients undergoing open AAA repair. A 6-week remote prehabilitation programme for AAA patients scheduled repair is feasible and improves functional capacity. Introducing a neuromuscular electrical stimulation device as an adjunct to rehabilitation for general and vascular patients is acceptable and safe.
Conclusion
Frailty is associated with worse outcomes for patients undergoing repair. Remote prehabilitation of AAA patients is feasible and can potentially improve outcomes following repair. The use of NMES as an adjunct to rehabilitation has the potential to enhance recovery following surgery and should be further explored. This thesis provided new evidence to support a national multicentre study to investigate novel interventions aimed at improving outcomes of AAA patients.Open Acces
