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High-precision and low-depth quantum algorithm design for eigenstate problems
No full textEstimating the eigenstate properties of quantum systems is a long-standing, challenging problem for both classical and quantum computing. Existing universal quantum algorithms typically rely on ideal and efficient query models (e.g. time evolution operator or block encoding of the Hamiltonian), which, however, become suboptimal for actual implementation at the quantum circuit level. Here, we present a full-stack design of quantum algorithms for estimating the eigenenergy and eigenstate properties, which can achieve high precision and good scaling with system size. The gate complexity per circuit for estimating generic Hamiltonians’ eigenstate properties is O(˜ log ¯¹), which has a logarithmic dependence on the inverse precision . For lattice Hamiltonians, the circuit depth of our design achieves near-optimal system-size scaling, even with local qubit connectivity. Our full-stack algorithm has low overhead in circuit compilation, which thus results in a small actual gate count (cnot and non-Clifford gates) for lattice and molecular problems compared to advanced eigenstate algorithms. The algorithm is implemented on IBM quantum devices using up to 2,000 two-qubit gates and 20,000 single-qubit gates, and achieves high-precision eigenenergy estimation for Heisenberg-type Hamiltonians, demonstrating its noise robustness
Metabolic flux analysis revealed key roles of ArcB in ADI pathway and IlvC in BCAA biosynthesis during Streptococcus suis anaerobic growth and infection
No full textCritical metabolic enzymes and pathways specific to bacterial adaptation in different host microenvironments directly contribute to bacterial pathogenicity. In this study, a virulent strain of the important zoonotic pathogen Streptococcus suis was found to show enhanced growth under anaerobic conditions compared to aerobic conditions. Transcriptomic analysis found a significant suppression of many central metabolic genes during anaerobic growth of S. suis. The transcriptomic data were used to reconstruct a genome-scale metabolic network to assess the distribution of metabolic fluxes in S. suis under different conditions. Significant activation of the arginine deiminase (ADI) and branched-chain amino acid (BCAA) biosynthesis pathways was identified. Gene deletion mutants of arcB and ilvC participating in these two pathways, respectively, were constructed. Compared to the wild-type strain, the ΔarcB mutant showed more significant growth deficiency under anaerobic conditions than under aerobic conditions. Accumulation of ATP and NH3, the metabolites of the ADI pathway, was significantly higher when S. suis was cultured under anaerobic conditions, and this effect was attenuated in the ΔarcB mutant. The knockout of IlvC of the BCAA pathway disrupted the normal growth of S. suis in valine- and isoleucine-limited medium under anaerobic conditions. Both ΔarcB and ΔilvC showed attenuation in mice with decreased lethality, bacterial loads in tissues, and cytokine levels in serum, with the hypoxia-induced gene up-regulated in tissues. Therefore, ADI and BCAA pathways are critical for S. suis survival in response to hypoxia and infection in vivo, with ArcB and IlvC being promising drug targets
Sp140L functions as a herpesvirus restriction factor suppressing viral transcription and activating interferon- stimulated genes
No full textHerpesviruses, including Epstein–Barr virus (EBV) – a human oncogenic virus and essential trigger of multiple sclerosis – must bypass host DNA-sensing mechanisms to establish lifelong, latent infection. Therefore, herpesviruses encode viral proteins to disrupt key host factors involved in DNA sensing and viral restriction. The first viral latency protein expressed, EBNA-LP, is essential for transformation of naïve B cells and establishment of viral gene expression, yet its role in evading host defenses remains unclear. Using single-cell RNA sequencing of EBNA-LP Knockout (LPKO)-infected B cells, we reveal an antiviral response landscape implicating the “speckled proteins” as key cellular restriction factors countered by EBNA-LP. Specifically, loss of Sp100 or the primate-specific Sp140L reverses the restriction of LPKO, suppresses a subset of canonically interferon-stimulated genes, and restores transcription of essential latent viral genes and cellular proliferation. Notably, we also identify Sp140L as a restriction target of the herpesvirus saimiri ORF3 protein, implying a role for Sp140L in immunity to other diverse DNA viruses. This study reveals Sp140L as a restriction factor that we propose links sensing and transcriptional suppression of viral DNA to an Interferon-independent innate immune response, likely relevant to all nuclear DNA viruses
Modelling the effects of immigration on the re-introduction of onchocerciasis
No full textBackground Onchocerciasis is a filarial neglected tropical disease targeted by the World Health Organization for elimination (interruption) of transmission (EOT), principally by mass drug administration (MDA) with ivermectin. Variable effectiveness and success of MDA,
among other factors, has led to a markedly heterogeneous contemporary spatial landscape of
endemicity and transmission, with some foci having achieved or nearing EOT, while in others, transmission persists despite decades of MDA or has only recently been identified. Communities reaching EOT or free from infection are thus vulnerable to re-introduction of
infection imported by immigrants from areas with ongoing transmission.
Methods We use the stochastic, individual-based EPIONCHO-IBM transmission model to quantify the risk of transmission persistence resulting from importation events and characterise the dynamics of ensuing onchocerciasis outbreaks in terms of microfilarial
prevalence (in all ages) and anti-Ov16 seroprevalence (in children aged 5-9 years) in infection-free communities with local populations of blackfly vectors.
Results We show how the vulnerability of infection-free communities depends on their population size, the local annual biting rate (ABR, number bites/person/year) and on the magnitude of importation events, defined by the number of immigrants arriving in the community and their worm burdens. We show that small communities with modest ABRs are particularly vulnerable to transmission persistence following importation, with risk exacerbated by the magnitude of infection importation. We illustrate that onchocerciasis outbreak dynamics can be protracted, with seroprevalence in children often taking substantially longer than the currently recommended 3-5 years of post-treatment surveillance
(PTS) to exceed 5%.
Conclusions Our findings highlight the vulnerability of infection-free communities to introduction/re-introduction of infection and suggest that proposed PTS durations may need to be extended and complemented with additional surveillance activities and migration
studies to detect and respond robustly to nascent outbreaks and sustain elimination
Competition and equilibrium in future global renewable hydrogen trade: a game-theoretic analysis
No full textGlobal renewable hydrogen trade is expected to play a key role in decarbonizing future energy systems. Yet hydrogen exporters may deviate from perfectly competitive behaviour to influence prices, similarly to the existing fossil fuel market, with important implications for consumer welfare and the pace of the energy transition. This study develops a global renewable hydrogen trade model that captures potential strategic interactions among exporters using a Stackelberg game-theoretic framework. The model is formulated as an Equilibrium Problem with Equilibrium Constraints (EPEC) and solved under three alternative equilibria: a profit-maximizing Nash equilibrium, a cost-minimizing Nash equilibrium, and a welfare-maximizing benchmark representing perfect competition. Results indicate that producers may strategically reduce their export quantities by up to 40 % relative to perfect competition to maximize profits. Such behaviour raises prices to a minimum of 4.5 USD/kg in 2050 across major import markets, thereby significantly eroding consumer surplus. Strategic behaviour of dominant exporters also shifts trade flows, reshaping the global allocation of hydrogen supply. Sensitivity analysis further reveals that financing costs play a key role in shaping strategic producers' behaviour, with lower financing costs helping to reduce prices and stimulate demand. These findings highlight the implications of imperfect competition in global hydrogen trade and suggest that policy measures may be needed to mitigate potential negative consequences
Reasoning about actual causality in answer set programming
No full textCausal models provide a formal framework for identifying and reasoning about the causes of observed phenomena, making them valuable for decision-support contexts where understanding causality is essential. Yet applying these models in practice requires automated tools for key reasoning tasks. We present an Answer Set Programming (ASP)-based tool that supports three core capabilities for all acyclic binary causal models: (1) checking whether an event is an actual cause of another; (2) finding all minimal subsets of a failed candidate that do qualify as causes; and (3) inferring all actual causes of an outcome without assuming any candidate. Our tool is the first to support all three tasks within a unified framework, guaranteeing minimal contingency sets and outperforming prior implementations in both runtime and memory. We describe the system’s design and report on an empirical evaluation using existing benchmarks
Interobserver reliability of Coronal Plane Alignment of the Knee (CPAK) phenotype classifcation
No full textAims
Coronal Plane Alignment of the Knee (CPAK) phenotyping is gaining momentum in research and clinical practice to understand individualized knee alignments and predict knee balance in total knee arthroplasty (TKA). The nine CPAK classes are based on joint line obliquity (JLO) and arithmetic hip-knee-ankle angle (aHKA), which are calculated using the medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA). This study aims to assess CPAK classification reproducibility, and analyze what level of angular error is associated with CPAK misclassification.
Methods
Two readers labelled 75 long-leg radiographs (LLRs) from the Osteoarthritis Initiative database for analyses of CPAK inter-reader reproducibility. A single reader then labelled and classified phenotypes for an aggregate total of 1,128 LLRs. Finally, Monte Carlo simulations were run based on 1,128-patient phenotype distribution and the inter-reader reproducibility statistics to understand how CPAK agreement rates were affected by the reproducibility of MPTA and LDFA measurements.
Results
There was excellent reproducibility in MPTA and LDFA measurements (mean absolute error: 0.41°/0.71°; and intraclass correlation coefficient: 0.96°/0.91°, respectively). These small angular deviations led to one-in-five disagreement in CPAK classification (20.0%; 95% CI 10.9% to 29.1%). An aHKA mean absolute error of < 0.1°, which is potentially unattainable, would be required to reduce inter-reader CPAK disagreement to below 95%.
Conclusion
CPAK phenotyping from long-leg radiographs may result in clinically significant rates of misclassification. CT imaging may improve reliability, particularly in cases where aHKA and JLO are near to discriminatory values
Modelling the impact of depth distributed plant water uptake on Soil-Plant-Atmosphere Interactions
No full textThe soil-plant-Atmosphere interaction (SPAI) significantly influences the safety and serviceability of engineering infrastructure by affecting pore water pressure (PWP) distribution. Rainfall and water infiltration increase PWPs, reducing soil strength, while evapotranspirationa "driven by evaporation and plant transpirationa "induces negative pore pressures (suction), enhancing soil strength and safety. However, vegetation can also pose serviceability challenges. During summer, root water uptake causes soil shrinkage, and in wet months, infiltration induces swelling. These cyclic volume changes can disrupt infrastructure, leading to road and track delays or closures. Accurate modelling of SPAI is therefore critical to understanding the effects of climate change and vegetation on soil hydraulic and mechanical behaviour. This study examines how surface and internal flow boundary conditions affect SPAI modelling within a fully coupled flow-deformation framework. While most recent research has focused on surface boundary conditions for hydrological fluxes, this paper evaluates the inclusion of internal boundary conditions to simulate vegetation transpiration. A comparative analysis assesses the safety and serviceability outcomes for models employing only surface boundary conditions versus those incorporating both surface and internal conditions
Using recursive attestation to scale trust in modern heterogeneous cloud architectures
No full textModern cloud infrastructures are increasingly complex, driven by heterogeneity, disaggregation, and dynamic service composition—exposing critical limits in traditional attestation models. These models struggle to scale when trust must span multiple domains and elastic services. We present scale-out attestation, a paradigm decoupling platform trust verification from app-level attestation. Our design introduces a recursive attestation framework leveraging abstract service identities and trusted deployment workflows: a single infrastructure agent verifies platforms via abstract policies, while services derive instance-agnostic identities enabling secure recursive dependency attestation. We implement the system on FractOS, a distributed OS for disaggregated data centers, and plan to extend Confidential Containers for practical deployment. Evaluation shows strong security with minimal overhead, enabling scalable confidential computing across heterogeneous and dynamic cloud environments
The impact of cuts in the US President's Emergency Plan for AIDS Relief funding for HIV pre-exposure prophylaxis in sub-Saharan Africa: a modelling study
No full textBackground
In January, 2025, the US Government issued a directive, pausing all foreign aid programmes. This directive included a 90-day pausing of all US President's Emergency Plan for AIDS Relief (PEPFAR) funding for HIV oral pre-exposure prophylaxis (PrEP) except for pregnant and breastfeeding women, with a return to funding for PrEP looking increasingly unlikely. We aimed to estimate the impact of a funding pause for PrEP on HIV infections in sub-Saharan Africa.
Methods
In this mathematical modelling study, we developed a static HIV transmission model incorporating PrEP, parameterised with estimates of population size, HIV prevalence and incidence, and PrEP effectiveness for different subpopulations (including key populations) in each PEPFAR-funded sub-Saharan African country. Key populations were men who have sex with men, female sex workers, transgender women, and people who inject drugs. We used PEPFAR reporting on numbers of people in different subpopulations returning for oral PrEP for each country in July to September, 2024, as the estimated number using oral PrEP provided by PEPFAR. For each country and subpopulation, we modelled the relative and absolute increase in new primary HIV infections resulting from removing this funded PrEP for a year and the number of secondary infections that could result from these primary infections during the next 5 years.
Findings
Towards the end of 2024, 719 384 individuals who were not breastfeeding or pregnant, including 205 868 people from key populations, received PEPFAR-funded PrEP across 28 sub-Saharan African countries. The estimated proportion of HIV-negative key population individuals receiving PEPFAR-funded PrEP (ie, the coverage) ranged from 2·6% (95% uncertainty interval 2·0–3·4) in people who inject drugs to 5·0% (4·5–5·9) in female sex workers. Estimated coverage among non-key population men was less than 0·1% (<0·1 to <0·1) and in women was 0·1% (0·1 to 0·1). Stopping PEPFAR's provision of PrEP for a year could lead to 6671 (5032–8192) additional new primary HIV infections, including 5663 (4146–7074) in key populations. Within key populations, this absolute increase corresponds to relative increases in new HIV infections of 0·8% (0·3–1·5) in people who inject drugs, 1·4% (0·8–2·3) in transgender women, 2·2% (1·3–3·0) in men who have sex with men, and 2·9% (1·8–4·4) in female sex workers. In Zambia, the country with the highest PEPFAR coverage across all key populations, this increase ranges from 7·8% (2·5–17·1) in people who inject drugs to 18·1% (9·7–33·2) in men who have sex with men. When considering secondary transmissions, we estimated that a 1-year pause could lead to 10 313 (7796–12 921) additional infections during the next 5 years.
Interpretation
Our projections show the substantial detrimental impacts that cuts to PEPFAR funding could have. Mitigation measures, including funding through alternative international donors or domestic government budgets, are needed to maintain and increase existing coverage levels of PrEP and therefore prevent the detrimental impact of PEPFAR's funding cuts, particularly in high coverage countries.
Funding
Wellcome Trust.
Translation
For the French translation of the abstract see Supplementary Materials section