New results on exhaustive search algorithm for motion estimation using adaptive partial distortion search and successive elimination algorithm

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The role of SARS-CoV-2 ORF8 protein ARKS motif on novobiocin binding

The discovery of the SARS-CoV-2 virus during the COVID-19 pandemic required scientists to develop medical solutions to reduce infectivity, severity of symptoms, and death. Although vaccines and drugs provided urgent assistance, the need to continue developing better drugs is necessary long term, and understanding the structure of the virus and finding potential inhibitors would prove vital to discovering solutions to this worldwide health problem. This experimental project focuses on targeting the unique accessory protein, Open Reading Frame 8 (ORF8) in SARS-CoV-2 through studying its interactions with a repurposable drug, novobiocin. Importantly, ORF8 specializes in helping evade immune system checks by downregulating major histocompatibility complex I (MHC-I) after infection, and is also involved in inflammatory responses from the cytokine storm, the most prominent cause of fatalities from the virus. Additionally, the ORF8 protein has been proposed to act as a histone mimic at the histone-H3 ARKS motif that causes post-translational changes in chromatin, further worsening these problems through gene transcription. Previous in silico and in vitro work from our lab has shown that novobiocin [Kd = 54.5 ± 3.14 μM] and three other computationally verified ligands (iohexol [Kd = 1185 ± 193 μM], kaempferol-7-O-glucoside [Kd = 135 ± 10.9 μM] & lercanidipine hydrochloride [Kd = 52.7 ± 5.71 μM]) bind to. To probe the role of Arg in the histone-H3 ARKS motif, specific mutation was done in position 52 from Arg to Met, Glu and Leu respectively. The above results in drastic changes in intermolecular forces such as opposing charge, polarity and different sizes of these side chains that negatively affect novobiocin’s ability to bind to the ORF8 pocket , which this research aims to experimentally prove this hypothesis. In silico analyses for the mutagenic ORF8 were initially found to require more energy to bind novobiocin to the ARKS motif than wild-type, but was still possible to dock according to Swissdock. Primers for the ORF8 R52 mutants were then designed and mutagenic plasmids were constructed and sequence verified. Each of the mutant ORF8 proteins was overexpressed, purified, and Kd values for binding to novobiocin were determined via intrinsic fluorescence spectroscopy and compared with wild-type binding. This data will help further understand the role of SARS-CoV-2 ORF8 protein ARKS motif and how its interactions affected novobiocin binding, potentially benefitting future studies attempting to repurpose novobiocin and other ligands for treatment of the spreading virus

Streptococcus pneumonia serotype 19A bacteremia in a child fully immunized with 10-valent pneumococcal conjugate vaccine

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Outcome measures of chronic arthritis in Hong Kong: comparison of the AIMS2 (Chinese) and WHO quality of life - brief form (WHOQOL-BREF) (HK)

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Changes in nasopharyngeal carriage and serotype distribution of antibiotic-resistant Streptococcus pneumoniae before and after the introduction of 7-valent pneumococcal conjugate vaccine in Hong Kong

This study assessed the changes in serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates in children before and after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Hong Kong. Nasopharyngeal specimens were collected from 1978 and 2211 children (ages, 2 to 6 years) attending day care centers or kindergartens in period 1 (1999-2000) and period 2 (2009-2010), respectively. Carriage of PCV7 serotypes decreased from 12.8% to 8.6% (P < 0.01). The relative contribution of PCV7 serotypes 14 and 18C had decreased, whereas that for non-PCV7 serotypes 19A, 6A, 6C, 23A, and 15B had increased. In period 2, PCV7 penetration rate (at least 1 dose) for children aged 2, 3, 4, and 5 years was 43%, 35.7%, 26.7%, and 20.4%, respectively. In multivariate analysis, PCV7 use was the only independent variable associated with fewer PCV7 serotype carriages (odds ratio 0.5; P = 0.001). In period 2, high rates of dual penicillin/erythromycin nonsusceptibility were found in serotypes 6B (77.3%), 14 (100%), 19F (100%), 23F (78%), 19A (75%), 6A (87.8%), 6C (59.3%), and 23A (78.9%).postprin

Robustness of Physics-Informed Neural Networks to Noise in Sensor Data

Physics-Informed Neural Networks (PINNs) have been shown to be an effective way of incorporating physics-based domain knowledge into neural network models for many important real-world systems. They have been particularly effective as a means of inferring system information based on data, even in cases where data is scarce. Most of the current work however assumes the availability of high-quality data. In this work, we further conduct a preliminary investigation of the robustness of physics-informed neural networks to the magnitude of noise in the data. Interestingly, our experiments reveal that the inclusion of physics in the neural network is sufficient to negate the impact of noise in data originating from hypothetical low quality sensors with high signal-to-noise ratios of up to 1. The resultant predictions for this test case are seen to still match the predictive value obtained for equivalent data obtained from high-quality sensors with potentially 10x less noise. This further implies the utility of physics-informed neural network modeling for making sense of data from sensor networks in the future, especially with the advent of Industry 4.0 and the increasing trend towards ubiquitous deployment of low-cost sensors which are typically noisier

Neuronavigated high-frequency repetitive transcranial magnetic stimulation for chronic post-stroke dysphagia: A randomized controlled study

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Molecular epidemiology and nasal carriage of Staphylococcus aureus and methicillin-resistant S. aureus among young children attending day care centers and kindergartens in Hong Kong

OBJECTIVES: To investigate the prevalence and molecular epidemiology of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) nasal carriage in children. METHODS: We collected nasal and nasopharyngeal swabs from 2211 children aged 2-5 years attending 79 day care centers (DCCs) and 113 kindergartens (KGs) in all 18 geographical districts in Hong Kong. RESULTS: The overall carriage rates of S. aureus and MRSA were 27.6% (95% confidence interval [CI], 24.8-28.5%) and 1.3% (95% CI, 0.8-1.8%), respectively. Molecular typing (staphylococcal cassette chromosome mec [SCCmec], sequence type [ST], clonal cluster [CC]) showed that all the 28 MRSA isolates had SCCmec IV (n = 13) or V (n = 15) including 12 isolates with community-associated-MRSA genotypes (ST59-IV/V, ST30-IV and ST88-V), 10 isolates with healthcare-associated-MRSA genotypes (ST45-IV/V, CC5-IV and ST630-V) and six isolates with novel genotypes (ST10-V and CC1-IV). Spa typing indicated that there was some within and between DCCs/KGs transmission of certain MRSA and methicillin-sensitive S. aureus strains but this was not extensive. CONCLUSION: Our findings indicate the potential for DCCs to be a reservoir for emerging MRSA genotypes and highlight the need to enhance education and infection control measures to reduce their cross-transmission in this population.postprin

LSA-PINN: Linear Boundary Connectivity Loss for Solving PDEs on Complex Geometry

We present a novel loss formulation for efficient learning of complex dynamics from governing physics, typically described by partial differential equations (PDEs), using physics-informed neural networks (PINNs). In our experiments, existing versions of PINNs are seen to learn poorly in many problems, especially for complex geometries, as it becomes increasingly difficult to establish appropriate sampling strategy at the near boundary region. Overly dense sampling can adversely impede training convergence if the local gradient behaviors are too complex to be adequately modelled by PINNs. On the other hand, if the samples are too sparse, existing PINNs tend to overfit the near boundary region, leading to incorrect solution. To prevent such issues, we propose a new Boundary Connectivity (BCXN) loss function which provides linear local structure approximation (LSA) to the gradient behaviors at the boundary for PINN. Our BCXN-loss implicitly imposes local structure during training, thus facilitating fast physics-informed learning across entire problem domains with order of magnitude sparser training samples. This LSA-PINN method shows a few orders of magnitude smaller errors than existing methods in terms of the standard L2-norm metric, while using dramatically fewer training samples and iterations. Our proposed LSA-PINN does not pose any requirement on the differentiable property of the networks, and we demonstrate its benefits and ease of implementation on both multi-layer perceptron and convolutional neural network versions as commonly used in current PINN literature.Comment: 11 pages, 7 figure

Molecular epidemiology and nasal carriage of Staphylococcus aureus and methicillin-resistant S. aureus among young children attending day care centers and kindergartens in Hong Kong

OBJECTIVES: To investigate the prevalence and molecular epidemiology of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) nasal carriage in children. METHODS: We collected nasal and nasopharyngeal swabs from 2211 children aged 2-5 years attending 79 day care centers (DCCs) and 113 kindergartens (KGs) in all 18 geographical districts in Hong Kong. RESULTS: The overall carriage rates of S. aureus and MRSA were 27.6% (95% confidence interval [CI], 24.8-28.5%) and 1.3% (95% CI, 0.8-1.8%), respectively. Molecular typing (staphylococcal cassette chromosome mec [SCCmec], sequence type [ST], clonal cluster [CC]) showed that all the 28 MRSA isolates had SCCmec IV (n = 13) or V (n = 15) including 12 isolates with community-associated-MRSA genotypes (ST59-IV/V, ST30-IV and ST88-V), 10 isolates with healthcare-associated-MRSA genotypes (ST45-IV/V, CC5-IV and ST630-V) and six isolates with novel genotypes (ST10-V and CC1-IV). Spa typing indicated that there was some within and between DCCs/KGs transmission of certain MRSA and methicillin-sensitive S. aureus strains but this was not extensive. CONCLUSION: Our findings indicate the potential for DCCs to be a reservoir for emerging MRSA genotypes and highlight the need to enhance education and infection control measures to reduce their cross-transmission in this population.postprin