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FABS: an extensible and high-performance digital twin framework of AI-driven financial systems
No full texthe study of complex AI systems in finance requires scalable digital twins, virtual laboratories for model verification, stress-testing, and counterfactual analysis. Agent-based modeling (ABM) is a primary tool for creating these digital twins, offering a bottom-up approach to capturing market-wide emergent phenomena. However, a major computational bottleneck hinders this work: existing simulation tools cannot efficiently model the large populations of interacting agents required for a high-fidelity digital replica of a financial system. The state-of-the-art simulator, MAXE, for instance, cannot accelerate a single, large-scale simulation. To address this, we introduce the Financial Agent-Based Simulator (FABS), an open-source C++ platform specifically designed as a high-performance engine for constructing and operating these large-scale digital twins. FABS combines three key features: a fine-grained parallel architecture to accelerate a single simulation, a dynamic graph-based optimization to reduce communication overhead, and an extensible callback system for simplified AI model integration. When benchmarked against MAXE in a large-scale fire sale scenario, FABS achieves a runtime speed-up of up to 12.52x. We validate its fidelity as a digital twin by showing that its synthetic data reproduces key stylized facts of financial markets, such as volatility clustering and fat-tailed returns. FABS provides a foundational tool for the financial AI community to build and analyze the complex agent-based digital twins needed to understand modern markets, at a scale that was previously computationally prohibitive
Laser Desorption-Rapid Evaporative Ionization Mass Spectrometry (LD-REIMS): a new tool for the high-throughput metabolomic and lipidomic profiling of live cells
No full textUnderstanding the dynamic cellular metabolism is essential for gaining deeper insights into inter- and intracellular functions. In recent years, mass spectrometry (MS) has become the technology of choice for the biochemical characterization and profiling of cell lines, particularly when coupled with separation techniques such as liquid chromatography (LC-MS). However, these methods typically involve extensive sample preparation with potent organic solvents, which is labor-intensive, time-consuming, and incompatible with direct analysis of intact, live cells. Here, we propose the use of the ambient ionization technique Laser Desorption-Rapid Evaporative Ionization Mass Spectrometry (LD-REIMS) incorporated in an automated platform, for the high-throughput profiling of live or frozen cell monolayers, with minimal pretreatment. Validation experiments using 10 breast and colorectal cancer cell lines confirmed high accuracy, repeatability, and molecular coverage of the method, with over 400 metabolites and lipids detected and identified, including saccharides, amino acids, fatty acids, and glycerophospholipids. Of these, 144 were further confirmed and quantified with LC-MS/MS and standard compounds. We also applied the method to establish lipidomic differences across the isogenic MCF10A cells harboring either WT or MUT PIK3CA. Finally, we conducted time-series experiments on hypoxic cells, which revealed significant dynamic changes in metabolism, including lactate accumulation due to anaerobic glycolysis
Robust 3D dynamic airspace sectorization: a multilayer graph-based approach
No full textThis paper presents a robust algorithm for three-dimensional dynamic airspace sectorization, introducing for the first time multilayer traffic networks in the study field. Distinct from widely used meta-heuristic algorithms, this approach delivers consistent results for the same traffic scenario, avoiding the instability of stochastic search techniques. This approach uses a graph-based model, taking the air traffic network as input, based on which we calculate traffic complexity. To quantify the complexity assigned to the network, we employ two parameters: one derives from the traffic scenarios based on flight vectors, and the other from the network topology. Using this complexity-weighted network as input, a multi-layer spectral clustering algorithm is applied to generate the desired number of communities. To achieve an ideal sector structure, we introduce a boundary refinement framework to produce smooth and tightly connected three-dimensional sectors. The performance of the proposed algorithm is validated using three Key Performance Indicators (KPIs): workload, sector flight time, and dynamic density, demonstrating its capability to generate more load-balanced sector configurations compared to both the current UK operational sectors and the widely used Voronoi diagram-based methods. The performance of the algorithm is evaluated through eight experiments under both peak and off-peak traffic conditions, including four-hour short-term and four six-hour long-term scenarios, with the number of target sectors kept consistent with the operational configuration. The reduced standard deviations and coefficients of variation of the KPIs indicate that the proposed sectorization achieves a more balanced distribution of traffic loads across sectors. This research provides Air Navigation Service Providers (ANSPs) with an automatic tool for three-dimensional airspace sectorization, enabling more balanced workload distribution while adapting to evolving air traffic flow patterns
Modelling adrenal steroid profiles to inform monitoring guidance in congenital adrenal hyperplasia
No full textBackground
There is no consensus on how to monitor adrenal androgens in Congenital Adrenal Hyperplasia (CAH).
Methods
Modelling of serum and salivary steroid profiles in healthy participants and patients with CAH randomised to either standard treatment or modified-release hydrocortisone hard capsules (MRHC).
Findings
Changes in serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) paralleled each other in healthy participants (n = 19) and patients with CAH (n = 122). However, healthy participants had similar absolute levels of 17OHP and A4 whereas patients with CAH had proportionally higher levels of 17OHP. Cross-correlation showed no lag between serum 17OHP and A4. In CAH, Bayesian multiple change point analysis converged on a 17OHP of 4.5 nmol/l below which in proportion to 17OHP the A4 is lower. Patients on standard treatment had a morning peak in 17OHP and A4 whereas patients on MRHC had relatively flat profiles. Salivary androgens including 11-ketotestosterone correlated with serum 17OHP and A4 in female patients (r = 0.7 to 0.9).
Interpretation
In CAH, elevated 17OHP drives the production of A4. High A4 reflects poor control, but low A4 does not indicate overtreatment. Accepting 17OHP is higher than A4, both measurements give similar reflection of control, and a 17OHP <38 nmol/l (1250 ng/dl) was associated with an A4 in the normal range <5 nmol/l (143 ng/dl) in 95% of patients and in clinical trials was used to define good control. On MRHC, which controls androgen levels over 24 h, a single sample of 17OHP and/or A4 can be used to monitor control. Salivary measurements reflect similar results to serum.
Funding
Diurnal; MRC; NIH; NIHR
Directing protein modification in living systems with bifunctional molecules
No full textOver the past two decades, protein S-acylation (also known as S-palmitoylation, or palmitoylation) has emerged as an essential regulator of key signalling pathways. S-Acylation is a reversible post-translational modification (PTM) that consists of the attachment of a fatty acid to a protein cysteine via a labile thioester linkage. In humans, S-acylation is catalysed by a dedicated class of 23 S-acyltransferases in the zinc-finger domain and DHHC motif-containing protein (ZDHHC) family. Unlike other classes of protein lipidation, S-acylation is reversible as the cleavage of the thioester bond is catalysed by hydrolases.
The addition of a fatty acid to a protein dramatically increases the hydrophobicity at the S-acylated site. This modification is unique among PTMs in that it establishes direct physical interactions between proteins and cell membranes. Notably, over 150 oncoproteins are known to undergo S-acylation, and multiple S-acyltransferases have been shown to regulate processes such as cancer cell proliferation and invasion. Modulating protein S-acylation could present a novel therapeutic approach to target otherwise intractable oncoproteins through the control of their membrane association and subcellular trafficking.
This project explores the feasibility of using proximity-induced pharmacology to induce proximity between a protein of interest (POI) and a specific S-acyltransferase, thereby directing the S-acylation of the POI. These S-acylation-inducing molecules are composed of a ligand for the protein substrate linked to a non-inhibitory ligand for a ZDHHC enzyme. The resulting bifunctional molecule can be expected to modulate protein S-acylation in cells and could offer a novel approach to block the subcellular trafficking of oncoproteins by anchoring them to a specific subcellular membrane.
In summary, this thesis presents a methodology for the rational design of small-molecule inducers of S-acylation, for the identification by chemical proteomics of protein targets amenable to proximity-induced S-acylation and proposes a workflow for the validation of potential future inducers of S-acylation.Open Acces
Formation of giant high-grade hypogene porphyry copper deposits during phyllic to advanced argillic alteration: textural evidence from automated SEM mapping at the resolution and Hugo Dummett North deposits
No full textDetailed core logging, combined with TESCAN TIMA mineral quantification at two globally significant, high-grade porphyry deposits – Resolution, USA, and Hugo Dummett North, Mongolia – indicate that most chalcopyrite ± bornite-pyrite is intergrown with muscovite that overprints earlier potassic alteration assemblages containing biotite and/or K-feldspar. Copper grades increase with the intensity of muscovite overprint on primary potassic assemblages supporting a link between high-grade Cu mineralization and phyllic alteration. Another zone of high-grade Cu mineralization occurs in the upper parts of the phyllic alteration zone and/or within later advanced argillic alteration, associated with high-sulfidation bornite ± digenite ± covellite ± chalcocite-pyrite assemblages, that partly replace earlier chalcopyrite. These two high grade domains have comparable features in many other significant high-grade Cu porphyry deposits (Chuquicamata, Rosario, MMH, Onto, Butte) – all strongly telescoped systems that host significant amounts of high-grade Cu mineralization in phyllic and/or advanced argillic alteration that overprint potassic alteration. We suggest there are at least three reasons for the development of high-grade hypogene ore in telescoped porphyry systems: (1) rapid unroofing and exhumation can generate steep thermal gradients, promoting a rapid decrease in Cu solubility and efficient precipitation of sulfides; (2) rapid, syn-mineralization exhumation and magma doming when the rock mass behaves in an increasingly brittle fashion, create significant permeability in late stages of porphyry systems; (3) telescoping during syn-mineralization exhumation leads to overprinting of early sulfide assemblages by late-stage acidic and oxidized hydrothermal fluids that remobilize and concentrate early Cu, leading to the precipitation of sulfides with high Cu/S ratios. We conclude that the coincidence of rapid exhumation and long-lived hydrothermal activity exerts a first order control on the formation of high-grade hypogene porphyry Cu mineralization
Spontaneous imbibition and forced water injection in mixed-wet multiscale oolitic limestone studied through the differential imaging-based porous plate technique
No full textUnderstanding imbibition in multiscale porous carbonates is essential for predicting fluid distribution in subsurface applications. We measured the capillary pressure for spontaneous imbibition and forced water injection in a mixed-wet multiscale oolitic limestone with distinct macro-, intermediate-size-, and micropore structure using the differential imaging-based porous plate (DIPP) technique. Spontaneous imbibition was found to occur through water-wet micropore channels, whereas forced water injection was dominated by the flow in mixed-wet and oil-wet macro-pores with residual oil found in pores of intermediate size. The analysis of contact angle, curvature, macro-pore occupancy, and overall water Amott index demonstrated mixed-wet-to-oil-wet conditions, resulting in a percolation-like advance during forced water injection. The water Amott index calculated on each pore size classification indicated water-wet micropores and oil-wet intermediate-size- and macro-pores. Our results highlight the role of micropores in sustaining water flow at low saturation and the role of intermediate-size-pores in retaining residual oil, advancing the predictive understanding of fluid behavior in carbonate reservoirs
Single-cell RNA-seq reveals aberrant airway epithelial- immune cell crosstalk in pulmonary fibrosis
No full textBackground
Epithelial-immune cell interactions are crucial in the regulation of pulmonary immune responses. Emerging evidence suggests that cell populations lining the airways may play a pivotal role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a disease characterised by progressive scarring of the lung parenchyma. We profiled the cellular landscape of the airway mucosal niche in incident cases of IPF to understand early-stage events contributing to disease development.
Methods
Single-cell RNA-sequencing was used to explore cellular heterogeneity in proximal airway brushings from seven healthy controls and nine patients with newly diagnosed IPF. In-depth bioinformatics analysis was used to interrogate changes in cell populations and cell-cell communication in IPF patients compared to controls.
Results
We show a relative increase in the abundance of airway macrophage subsets in IPF compared to healthy controls, and disease-specific changes in their transcriptional profile. Increased frequency of airway macrophages and proliferating macrophages was associated with more extensive disease at baseline quantified by the composite physiological index and radiological severity of traction bronchiectasis. Monocyte-derived macrophages were significantly enriched at baseline in IPF patients who had disease progression at 12 months. Using CellChat we exposed differences in cell-cell communication between airway epithelial cells, airway macrophages and T cells in IPF. We identified dysregulation in signalling pathways such as SEMA3, ANXA1 and DESMOSOME which modulate airway epithelial-macrophage interactions, potentially driving disease pathology.
Conclusions
Airway epithelial cells and macrophages may play a key role in orchestrating the early immunopathology of IPF, and these data support further exploration of novel, airway-focused therapeutic targets in IPF
Two-phase flow and solute transport in porous rocks for surfactant/polymer coreflooding applications
No full textMulti-phase flow and transport in porous media plays a critical role in many established and developing fields. Among which, subsurface applications - such as CO2 sequestration and enhanced oil recovery (EOR) - have been, and continue to be, of great industrial relevance. Within EOR techniques, surfactant/polymer flooding is an attractive option given its great recovery potential - offering an avenue for the maximisation of available resources. Despite this, difficulties in translating laboratory scale recoveries to the field scale have been prevalent. A key element within this upscaling workflow are corefloods. Here, fluid combinations and injection schemes are tested with - via primarily the interpretation of outlet samples - the goal of extracting parameters for use in reservoir simulations. Given the complex nature of the flooding process, and the often conflicting physical phenomena, designing a successful system and extracting meaningful parameters can prove difficult given uncertainty in the in-situ behaviour. To address this, direct imaging techniques have a potential to help alleviate many of these difficulties by offering a less restricted and more comprehensive viewpoint. The primary goal of this work is the inclusion of two imaging techniques, X-ray computed tomography (CT) and positron emission tomography (PET), into surfactant/polymer coreflooding studies. To this aim, an experimental set-up and combination of fluids was devised to allow for successful and representative corefloods - further complemented by a number of numerical tools. The surfactant/polymer corefloods were of tertiary recovery nature and, through the use of X-ray CT, three-dimensional saturation profiles were reconstructed with which the effect of core size, surfactant choice and heterogeneity were investigated. On the other hand, in combination with PET, the transport of solute subject to a dynamically changing saturation was also investigated. Overall, direct imaging applied to surfactant/polymer corefloods is showcased, ultimately intending to display both its utility and versatility
“I think it is our responsibility, but not solely our responsibility”: a qualitative study exploring teachers’ perspectives on promoting mental health in Northwest London primary schools
No full textIn England, 1 in 5 children and young people (CYP; aged 8-25 years) has a probable mental disorder with higher rates among those living in poverty, and among white children compared with other ethnic groups. However, in the UK, research shows that the prevalence of mental health conditions and associated service use differs among some ethnic minority groups (e.g., Asian) suggesting potential unmet mental health need. Early interventions have been shown to improve life outcomes, and UK government policies encourage the promotion of mental health and wellbeing in schools and colleges, but poor mental health continues to rise. Despite evidence showing that mental health problems occur as early as age 5 years, limited research focusses on primary schools (children aged 5-10 years). Northwest London (NWL), UK, is a diverse region in London, is in the top 20% most deprived, and has a high demand for CYP mental health services. The aim of our study was to explore teachers’ perspectives of promoting positive mental health in NWL primary schools. We created a semi-structured interview based on policy guidance. Nine teachers were recruited and interviewed during June and July 2024. Thematic analysis identified six overarching themes: (1) mental health needs; (2) responsibility; (3). factors contributing to poor mental health; (4). barriers and (5) facilitators to providing support; and (6) collaboration. Subthemes included lack of skills to address the broad spectrum of mental health needs, funding, resources, and lack of support systems to ensure all children receive the right support at the right time. Our study highlights implementation gaps for promoting mental health policy in diverse real-world settings, and suggests that whilst schools play an important role for early mental health intervention, wider complexities limit sufficient support provision. Our findings have potential implications for mental health promotion policies in school settings