The comprehension of classifiers in Cantonese-speaking preschool children

Also available in print.Thesis (B.Sc)--University of Hong Kong, 2005.A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2005.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

CADSim: Robust and Scalable in-the-wild 3D Reconstruction for Controllable Sensor Simulation

Realistic simulation is key to enabling safe and scalable development of % self-driving vehicles. A core component is simulating the sensors so that the entire autonomy system can be tested in simulation. Sensor simulation involves modeling traffic participants, such as vehicles, with high quality appearance and articulated geometry, and rendering them in real time. The self-driving industry has typically employed artists to build these assets. However, this is expensive, slow, and may not reflect reality. Instead, reconstructing assets automatically from sensor data collected in the wild would provide a better path to generating a diverse and large set with good real-world coverage. Nevertheless, current reconstruction approaches struggle on in-the-wild sensor data, due to its sparsity and noise. To tackle these issues, we present CADSim, which combines part-aware object-class priors via a small set of CAD models with differentiable rendering to automatically reconstruct vehicle geometry, including articulated wheels, with high-quality appearance. Our experiments show our method recovers more accurate shapes from sparse data compared to existing approaches. Importantly, it also trains and renders efficiently. We demonstrate our reconstructed vehicles in several applications, including accurate testing of autonomy perception systems.Comment: CoRL 2022. Project page: https://waabi.ai/cadsim

Disulfide bond reduction and exchange in C4 domain of von Willebrand factor undermines platelet binding

Background The von Willebrand factor (VWF) is a key player in regulating hemostasis through adhesion of platelets to sites of vascular injury. It is a large, multi-domain, mechano-sensitive protein that is stabilized by a net of disulfide bridges. Binding to platelet integrin is achieved by the VWF-C4 domain, which exhibits a fixed fold, even under conditions of severe mechanical stress, but only if critical internal disulfide bonds are closed. Objective To determine the oxidation state of disulfide bridges in the C4 domain of VWF and implications for VWF’s platelet binding function. Methods We combined classical molecular dynamics and quantum mechanical simulations, mass spectrometry, site-directed mutagenesis, and platelet binding assays. Results We show that 2 disulfide bonds in the VWF-C4 domain, namely the 2 major force-bearing ones, are partially reduced in human blood. Reduction leads to pronounced conformational changes within C4 that considerably affect the accessibility of the integrin-binding motif, and thereby impair integrin-mediated platelet binding. We also reveal that reduced species in the C4 domain undergo specific thiol/disulfide exchanges with the remaining disulfide bridges, in a process in which mechanical force may increase the proximity of specific reactant cysteines, further trapping C4 in a state of low integrin-binding propensity. We identify a multitude of redox states in all 6 VWF-C domains, suggesting disulfide bond reduction and swapping to be a general theme. Conclusions Our data suggests a mechanism in which disulfide bonds dynamically swap cysteine partners and control the interaction of VWF with integrin and potentially other partners, thereby critically influencing its hemostatic function

Streptococcus pneumoniae DNA Initiates Type I Interferon Signaling in the Respiratory Tract

The mucosal epithelium is the initial target for respiratory pathogens of all types. While type I interferon (IFN) signaling is traditionally associated with antiviral immunity, we demonstrate that the extracellular bacterial pathogen Streptococcus pneumoniae activates the type I IFN cascade in airway epithelial and dendritic cells. This response is dependent upon the pore-forming toxin pneumolysin. Pneumococcal DNA activates IFN-β expression through a DAI/STING/TBK1/IRF3 cascade. Tlr4−/−, Myd88−/−, Trif−/−, and Nod2−/− mutant mice had no impairment of type I IFN signaling. Induction of type I IFN signaling contributes to the eradication of pneumococcal carriage, as IFN-α/β receptor null mice had significantly increased nasal colonization with S. pneumoniae compared with that of wild-type mice. These studies suggest that the type I IFN cascade is a central component of the mucosal response to airway bacterial pathogens and is responsive to bacterial pathogen-associated molecular patterns that are capable of accessing intracellular receptors

Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.

Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases