Filoviruses pose a threat to individuals and the global community as pathogens of pandemic potential. The scientific community faces an ongoing challenge of developing effective vaccines with unpredictable outbreaks concentrated in countries with lower healthcare resources. Given these limitations, it is important to ensure that existing filovirus research is used as efficiently as possible. To […]
Cannot, Should Not, Did Anyway: Benchmarking Constraint Enforcement Failure in Frontier LLMs
Large language models are typically evaluated under fixed instruction contexts, implicitly treating correct refusal as a stable model property. We show that this obscures a critical failure mode: models often recognize that a request should be refused, yet comply when the surrounding instructions exert sufficient pressure. To measure this behavior directly, we introduce FrameProbe, a […]
Integrated Proteomic and Network Analysis Reveals Dysregulated Pathways and Candidate Proteins in Multiple Myeloma Progression
Background: Multiple myeloma (MM) remains incurable despite therapeutic advances, reflecting limited understanding of the molecular mechanisms underlying disease initiation and progression. MM develops through asymptomatic precursor stages, monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM). This study aimed to investigate protein changes associated with disease progression and, through a further integrative approach, […]
The 16p11.2 microdeletion enhances gene expression variability between human IPSC derived forebrain interneuron progenitor cells in culture.
The 574 kilobase pair 16p11.2 microdeletion raises a person’s odds for neurodevelopmental and energy balance conditions, particularly autism and obesity. There is considerable clinical heterogeneity and how much this reflects genetic versus environmental or stochastic factors is unclear. Forebrain interneurons originate from progenitors residing in the ventricular zone of the foetal ventral telencephalon and their […]
Automated GenePy Gene-Burden Computation via a Reproducible Nextflow Workflow Integrated with the Genomics England (GEL) Lifebit Platform
Interpretation of rare-disease genomes remains constrained by variant-centric analytical frameworks that insufficiently capture the cumulative impact of multiple variants within a gene. GenePy provides an individual-level, gene-based burden metric that integrates variant consequence, allele frequency, and zygosity into a unified quantitative score, enabling a transition from discrete variant annotation to aggregated gene-level interpretation. In the […]
Single-Molecule Activity Profiling of Glycosidase Proteoforms Using Water-Soluble Fluorogenic Probes
In this study, we report a series of highly water-soluble fluorogenic probes for glycosidases useful for microdevice-based single-molecule enzyme activity profiling (SEAP). The assay was able to detect trace glycosidase activities in blood with high sensitivity and with proteoform resolution. This platform revealed the potential of -mannosidase as sensitive blood-based liquid-biopsy biomarkers for liver injury, […]
Collagen Rope Trick: Cell-Laden Fibre Assembly at 1 Liquid Interfaces
Tissues and organs in living organisms represent centimeter-scale hierarchical architectures comprising nano- to microscale, uniaxially aligned extracellular matrix (ECM) fibres with high mechanical strength, integrated with cellular components, as exemplified in tendon, skin, cartilage, bone, and blood vessels. Here, we present a liquid-liquid interfacial spinning method to produce highly uniaxially aligned, centimeter-scale collagen fibres. The […]
Single-Molecule Activity Profiling of Glycosidase Proteoforms Using Water-Soluble Fluorogenic Probes
In this study, we report a series of highly water-soluble fluorogenic probes for glycosidases useful for microdevice-based single-molecule enzyme activity profiling (SEAP). The assay was able to detect trace glycosidase activities in blood with high sensitivity and with proteoform resolution. This platform revealed the potential of -mannosidase as sensitive blood-based liquid-biopsy biomarkers for liver injury, […]
Cannot, Should Not, Did Anyway: Benchmarking Constraint Enforcement Failure in Frontier LLMs
Large language models are typically evaluated under fixed instruction contexts, implicitly treating correct refusal as a stable model property. We show that this obscures a critical failure mode: models often recognize that a request should be refused, yet comply when the surrounding instructions exert sufficient pressure. To measure this behavior directly, we introduce FrameProbe, a […]
Proteomic Identification of Pig Xenoantigens for Clinical Xenotransplantation
Xenotransplantation using genetically engineered pig organs offers a promising solution to the shortage of donor organs for life-saving transplants. However, human preformed antibodies against unknown pig xenoantigens remain a significant barrier to successful xenotransplantation. Current methods for characterizing these antibodies or xenoantigens are limited to cellular-level crossmatch assays. In this study, we developed a novel […]
Causal Network Mapping of sEEG Identifies Compact Epileptogenic Targets Concordant with Seizure Freedom: Multicenter Validation in 60 Patients
Background and Purpose: Drug resistant epilepsy (DRE) affects approximately 15 million people worldwide, and surgery remains the only curative option. A key challenge in predicting outcomes is the lack of standardized, quantitative tools to help distinguish seizure driver regions from responder regions during stereoelectroencephalography (sEEG) recordings. We validated the CN Suite, a computational platform that […]
Automated GenePy Gene-Burden Computation via a Reproducible Nextflow Workflow Integrated with the Genomics England (GEL) Lifebit Platform
Interpretation of rare-disease genomes remains constrained by variant-centric analytical frameworks that insufficiently capture the cumulative impact of multiple variants within a gene. GenePy provides an individual-level, gene-based burden metric that integrates variant consequence, allele frequency, and zygosity into a unified quantitative score, enabling a transition from discrete variant annotation to aggregated gene-level interpretation. In the […]