A5001890117- Enzyme Structure and Function
- Nuclear Physics and Applications
- Protein Structure and Dynamics
- Advanced NMR Techniques and Applications
- Amyloidosis: Diagnosis, Treatment, Outcomes
- X-ray Diffraction in Crystallography
- Erythrocyte Function and Pathophysiology
- Biotin and Related Studies
- Mass Spectrometry Techniques and Applications
- Bone health and treatments
- Electronic and Structural Properties of Oxides
- Rare-earth and actinide compounds
- Nanoparticle-Based Drug Delivery
- Respiratory viral infections research
- Neuroendocrine Tumor Research Advances
- Lipid Membrane Structure and Behavior
- SARS-CoV-2 and COVID-19 Research
- Protein Kinase Regulation and GTPase Signaling
- Topic Modeling
- Crystallization and Solubility Studies
- Inhalation and Respiratory Drug Delivery
- Crystallography and Radiation Phenomena
- Chemical Reactions and Isotopes
- Magnetism in coordination complexes
- Quantum, superfluid, helium dynamics
University of Toronto
2023
Keele University
2016-2019
Institut Laue-Langevin
2017
Nottingham Trent University
2016
University of Southampton
2016
Human transthyretin (TTR) is implicated in several fatal forms of amyloidosis. Many mutations TTR have been identified; most these are pathogenic, but some offer protective effects. The molecular basis underlying the vastly different fibrillation behaviours mutants poorly understood. Here, on neutron crystallography, native mass spectrometry and modelling studies, we propose a mechanism whereby can form amyloid fibrils via parallel equilibrium partially unfolded species that proceeds favour...
It is well established that the formation of transthyretin (TTR) amyloid fibrils linked to destabilization and dissociation its tetrameric structure into insoluble aggregates. Isotope labeling used for study TTR by NMR, neutron diffraction, mass spectrometry (MS). Here MS, thioflavin T fluorescence, crystallographic data demonstrate while X-ray structures unlabeled deuterium-labeled are essentially identical, subunit exchange kinetics accelerated deuterated protein. However, a slower noted...
The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue impact the lives health of people across world for foreseeable future. rollout vaccines provided highly anticipated relief, but effective therapeutics are required further reduce risk severity infections. Monoclonal antibodies have been shown be as SARS-CoV-2, new variants concern (VoC) emerge, their utility use waned due limited or no efficacy against these variants. Furthermore, cumbersome...
Abstract It is well established that the formation of transthyretin (TTR) amyloid fibrils linked to destabilization and dissociation its tetrameric structure into insoluble aggregates. Isotope labeling used for study TTR by NMR, neutron diffraction, mass spectrometry (MS). Here MS, thioflavin T fluorescence, crystallographic data demonstrate while X‐ray structures unlabeled deuterium‐labeled are essentially identical, subunit exchange kinetics accelerated deuterated protein. However, a...
The application of IR spectroscopy to the characterization and quality control samples used in neutron crystallography is described. While a growing field, limited availability beamtime means that there may be delay between crystallogenesis data collection. Since essentially all crystallographic work carried out using D2O-based solvent buffers, particular concern for these experiments possibility H2O back-exchange across reservoir or capillary sealants. This limit scattering length density...
Building on the foundations of language modeling in natural processing, Next Token Prediction (NTP) has evolved into a versatile training objective for machine learning tasks across various modalities, achieving considerable success. As Large Language Models (LLMs) have advanced to unify understanding and generation within textual modality, recent research shown that from different modalities can also be effectively encapsulated NTP framework, transforming multimodal information tokens...
Human transthyretin (TTR) is a 55 kDa homotetramer plasma transport protein for thyroxine T4 and retinol, through the association with retinol binding protein, in blood cerebrospinal fluid.TTR mutants have been implicated familial amyloid polyneuropathy (FAP), life-threatening multisystem disorder characterised by extracellular depositions of fibrils.It an irreversible progressive disease fatal within 10 years onset.There are currently more than 80 pathogenic mutations reported TTR.These...