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Tumour mutational burden is overestimated by target cancer gene panels

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Journal of the National Cancer Center 2023年第1期3卷 56-64页

作者： Hu Fang Johanna Bertl Xiaoqiang Zhu Tai Chung Lam Song Wu David J.H.Shih Jason W.H.Wong School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina South China Hospital Health Science CenterShenzhen UniversityShenzhenChina Department of Mathematics Aarhus UniversityAarhusDenmark Department of Clinical Oncology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Background:Tumour mutational burden(TMB)has emerged as a predictive marker for responsiveness to immune checkpoint inhibitors(ICI)in multiple tumour *** can be calculated from somatic mutations detected from whole exome or targeted panel sequencing *** mutations are unevenly distributed across the cancer genome,the clinical implications from TMB calculated using different genomic regions are not ***:Pan-cancer data of 10,179 samples were collected from The Cancer Genome Atlas cohort and 6,831 cancer patients with either ICI or non-ICI treatment outcomes were derived from published *** was calculated as the count of non-synonymous mutations and normalised by the size of genomic *** method,linear regression and Poisson calibration models are used to unify TMB from different gene ***:We found that panels based on cancer genes usually overestimate TMB compared to whole exome,potentially leading to misclassification of patients to receive *** overestimation is caused by positive selection for mutations in cancer genes and cannot be completely addressed by the removal of mutational *** compared different approaches to address this discrepancy and developed a generalised statistical model capable of interconverting TMB derived from whole exome and different panel sequencing data,enabling TMB correction for patient stratification for ICI *** show that in a cohort of lung cancer patients treated with ICI,when using a TMB cutoffof 10 mut/Mb,our corrected TMB outperforms the original panel-based ***:Cancer gene-based panels usually overestimate TMB,and these findings will be valuable for unifying TMB calculations across cancer gene panels in clinical practice.

关键词： Tumour mutational burden Immune checkpoint inhibitor Immune response Biomarker

Variations between rice cultivars in iron and manganese plaque on roots and the relation with plant cadmium uptake

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Journal of Environmental Sciences 2010年第7期22卷 1067-1072页

作者： Jianguo Liu Changxun Cao Minghung Wong Zhijun Zhang Yuhong Chai School of Environmental and Safety Engineering Jiangsu Polytechnic University Changzhou 213164 China Croucher Institute for Environmental Sciences and Department of Biology Hong Kong Baptist University Hong Kong China

To understand certain mechanisms causing variations between rice cultivars with regard to cadmium uptake and tolerance, pot soil experiments were conducted with two rice cultivars of different genotypes under different soil Cd levels. The relationships between plant Cd uptake and iron/manganese （Fe/Mn） plaque formation on roots were investigated. The results showed that rice cultivars differed markedly in Cd uptake and tolerance. Under soil Cd treatments, Cd concentrations and accumulations in the cultivar Shanyou 63 （the genotype indica） were significantly higher than those in the cultivar Wuyunjing 7 （the genotype japonica）（P 〈 0.01, or P 〈 0.05）, and Shanyou 63 was more sensitive to Cd toxicity than Wuyunjing 7. The differences between the rice cultivars were the largest at relatively low soil Cd level （i.e., 10 mg/kg）. Fe concentrations in dithionite-citrate-bicarbonate root extracts of Shanyou 63 were generally lower than that of Wuyunjing 7, and the difference was the most significant under the treatment of 10 mg Cd/kg soil. The results indicated that the formation of iron plaque on rice roots could act as a barrier to soil Cd toxicity, and may be a ＂buffer＂ or a ＂reservoir＂ which could reduce Cd uptake into rice roots. And the plaque may contribute, to some extent, to the genotypic differences of rice cultivars in Cd uptake and tolerance.

关键词： rice (Orvza sativa L.) cadmium zenotype iron/manganese plaque

A comparative study on microstructure,nanomechanical and corrosion behaviors of AlCoCuFeNi high entropy alloys fabricated by selective laser melting and laser metal deposition

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Journal of Materials Science & Technology 2022年第36期131卷 221-230页

作者： Yaojia Ren Hong Wu Bin Liu Yong Liu Sheng Guo ZBJiao Ian Baker State Key Laboratory of Powder Metallurgy Central South UniversityChangsha 410083China Department of Industrial and Materials Science Chalmers University of TechnologyGothenburg SE-41296Sweden Department of Mechanical Engineering The Hong Kong Polytechnic UniversityHong Kong 999077China Thayer School of Engineering Dartmouth CollegeHanover NH 03755-8000United States

The present study investigated the microstructure,nanomechanics,and corrosion behavior of AlCoCuFeNi high entropy alloys fabricated by selective laser melting(SLM)and laser metal deposition(LMD).The microstructure of SLM-processed specimens was mainly composed of columnar-grained BCC matrix(^90μm in width)and Cu-rich twinned FCC *** columnar grains grew epitaxially along the building direction and exhibited a strong{001}*** comparison,a coarse columnar-grained BCC matrix(^150μm in width)with a strongertexture,rod-like B2 precipitates,and large core-shell structured FCC phases were formed in the LMD-processed specimens due to the higher heat accumulation ***,the LMD-processed specimens showed a lower hardness,wear resistance,and corrosion resistance,but higher creep resistance and reduced Young's modulus than the SLM-processed *** cracks occurred in both types of specimens,which could not be completely suppressed due to Cu segregation.

关键词： Selective laser melting Laser metal deposition High entropy alloys Nanomechanics Corrosion

Molecular Characterization of Plant Prevacuolar and Endosomal Compartments

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Journal of Integrative Plant Biology 2007年第8期49卷 1119-1128页

作者： Sheung Kwan Lam Yu Chung Tse Yansong Miao Hong-Ye Li Junqi Wang Sze Wan Lo Liwen Jiang Department of Biology and Molecular Biotechnology Program The Chinese University of Hong Kong Shatin New Territories Hong Kong China Institute of Plant Molecular Biology & Agricultural Biotechnology The Chinese University of Hong Kong Shatin New Territories Hong Kong China

Prevacuolar compartments （PVCs） and endosomal compartments are membrane-bound organelles mediating protein traffic to vacuoles in the secretory and endocytic pathways of plant cells. Over the years, great progress has been made towards our understanding in these two compartments in plant cells. In this review, we will summarize our contributions toward the identification and characterization of plant prevacuolar and endosomal compartments. Our studies will serve as important steps in future molecular characterization of PVC biogenesis and PVC-mediated protein traffickinq in plant cells.

关键词： BY-2 cells endosomal compartment prevacuolar compartment organelle proteomic vacuolar sorting receptor

Revisiting the Climatology of Atmospheric Blocking in the Northern Hemisphere

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Advances in Atmospheric Sciences 2013年第2期30卷 397-410页

作者： Ho Nam CHEUNG 周文 Hing Yim MOK Man Chi WU Yaping SHAO City University of Hong Kong Shenzhen research Institute Guy Carpenter Asia-Pacific Climate Impact Centre School of Energy and Environment City University of Hong Kong Hong Kong Observatory Institute for Geophysics and Meteorology University of Cologne

In addition to the occurrence of atmospheric blocking, the climatology of the characteristics of blocking events, including duration, intensity, and extension, in four seasons over the Northern Hemisphere was analyzed for the period 1950-2009. The seasonality and spatial variations of these characteristics were studied according to their longitudinal distributions. In general, there were sharp discrepancies in the blocking characteristics between winter and summer, and these differences were more prominent over the Atlantic and Pacific Oceans. The blocking not only occurred more frequently but also underwent stronger amplification in winter; likewise, the blocking occurred less frequently and underwent weaker amplification in summer. There are very strong interrelationships among different blocking characteristics, suggesting that they are supported by similar physical factors. In addition, the relationship between blocking over different regions and East Asian circulation was examined. Ural-Siberia is a major blocking formation region in all seasons that may exert a downstream impact on East Asia. The impact is generally weak in summer, which is due to its lower intensity and smaller duration. However, the extratropical circulation over East Asia in summer can be disturbed persistently by the frequent occurrence of blocking over the Asian continent or the Western Pacific. In particular, the blocking frequency over the Western Pacific significantly increased during the study period. This climatological information provides a background for studying the impact of blocking on East Asian circulation under both present and future climate conditions.

关键词： atmospheric blocking climatology seasonality East Asian circulation

Formation of brain map for spatial perception

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Formation of brain map for spatial perception

Impacts of pollution heterogeneity on population exposure in dense urban areas using ultra-fine resolution air quality data

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Ying-Shing CHAN Department of Physiology LKS Faculty of MedicineThe University of Hong Kong

＜正＞Establishment of functional neural network depends on precise synaptic integration at different stages of *** the central vestibular system of rats,we identified a sequence of maturation time at which neurons in the vestibular nucleus,inferior olive and thalamus responded to linear accelerations along the horizontal or vertical *** the vestibular nucleus,the age at which neurons responded to specific gravity-related directions was in corroboration with that at which the animal began to correct itself when *** changes in synaptic properties of these neurons were governed by ionotropic glutamate receptors and/or GABA *** change in synaptic property ocurred in correlation with the ability of vestibular nuclear neurons to encode spatial orientations. Perinatal blockade of these receptors in the vestibular nucleus led to derangement in the formation of spatial reference within the inferior olive and thalamus of adult *** impact of such perturbation on spatial orienting and motor learning behaviors during this critical period of susceptibility will be *** together,our results suggest that refinement of the developing vestibular circuitry during a postnatal critical period is crucial for coherent recognition of gravityrelated spatial orientations in the mature animal.

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Journal of Environmental Sciences 2023年第3期125卷 513-523页

作者： Wenwei Che Yumiao Zhang Changqing Lin Yik Him Fung Jimmy C.H.Fung Alexis KHLau Division of Environment and Sustainability The Hong Kong University of Science and TechnologyClear Water BayHong KongChina Department of Mathematics The Hong Kong University of Science and TechnologyClear Water BayHong KongChina Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyClear Water BayHong KongChina Guangdong-Hongkong-Macao Joint Laboratory of Collaborative Innovation for Environmental Quality Hong Kong University of Science and TechnologyClear Water BayHong KongChina

Traditional air quality data have a spatial resolution of 1 km or above, making it challenging to resolve detailed air pollution exposure in complex urban areas. Combining urban morphology, dynamic traffic emission, regional and local meteorology, physicochemical transformations in air quality models using big data fusion technology, an ultra-fine resolution modeling system was developed to provide air quality data down to street level. Based on one-year ultra-fine resolution data, this study investigated the effects of pollution heterogeneity on the individual and population exposure to particulate matter(PM_(2.5)and PM_(10)),nitrogen dioxide(NO_(2)), and ozone(O_(3)) in Hong Kong, one of the most densely populated and urbanized cities. Sharp fine-scale variabilities in air pollution were revealed within individual city blocks. Using traditional 1 km average to represent individual exposure resulted in a positively skewed deviation of up to 200% for high-end exposure individuals. Citizens were disproportionally affected by air pollution, with annual pollutant concentrations varied by factors of 2 to 5 among 452 District council Constituency Areas(DCCAs) in Hong Kong, indicating great environmental inequities among the population. Unfavorable city planning resulted in a positive spatial coincidence between pollution and population, which increased public exposure to air pollutants by as large as 46% among districts in Hong Kong. Our results highlight the importance of ultra-fine pollutant data in quantifying the heterogeneity in pollution exposure in the dense urban area and the critical role of smart urban planning in reducing exposure inequities.

关键词： Particulate matter Nitrogen dioxide Ozone Pollution heterogeneity Urban area

Optimal extent of fluorination enabling strong temperature-dependent aggregation, favorable blend morphology and high-efficiency polymer solar cells

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Science China Chemistry 2017年第4期60卷 545-551页

作者： Guofang Yang Zhengke Li Kui Jiang Jie Zhang Jianya Chen Guangye Zhang Fei Huang Wei Ma He Yan State Key Laboratory for Mechanical Behavior of Materials Xi 'an Jiaotong University Xi 'an 710049 China Institute of Polymer Optoelectronic Materials and Devices South China University of Technology Guangzhou 510640 China Department of Chemistry and Energy Institute The Hong Kong University of Science and Technology ClearWater Bay Kowloon Hong Kong China hkUST-Shenzhen research Institute Shenzhen 518057 China

Temperature-dependent aggregation is a key property for some donor polymers to realize favorable bulk-heterojunction(BHJ)morphologies and high-efficiency(>10%) polymer solar *** studies find that an important structural feature that enables such temperature-dependent aggregation property is the 2nd position branched alkyl chains sitting between two thiophene *** this report,we demonstrate that an optimal extent of fluorination on the polymer backbone is a second essential structural feature that enables the strong temperature-dependent aggregation *** compare the properties of three structurally similar polymers with 0,2 or 4 fluorine substitutions in each repeating unit through an in-depth morphological *** show that the non-fluorinated polymer does not aggregate in solution(0.02 mg mL^(-1) in chlorobenzene) at room temperature,which results in poor polymer crystallinity and extremely large polymer *** the other hand,the polymer with four fluorine atoms in each repeating unit exhibits an excessively strong tendency to aggregate,which makes it difficult to process and causes a large *** the polymer with two fluorine atoms in each repeating unit exhibits a suitable extent of temperature-dependent aggregation *** a result,its blend film achieves a favorable morphology and high power conversion *** provides another key design rationale for developing donor polymers with suitable temperature-dependent aggregation properties and thus high performance.

关键词： temperature-dependent aggregation fluorination morphology polymer solar cells

BRAIN IRON MISREGULATION: ONE OF INITIAL CAUSES OF NEURODEGENERATIVE DISORDERS

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BRAIN IRON MISREGULATION: ONE OF INITIAL CAUSES OF NEURODEGE...