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SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance:Implications for Antibody Therapy and Vaccinations against COVID-19

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Research 2024年第3期2023卷 1-15页

作者： Xiaoying ma Jady Liang Guangheng Zhu Preeti Bhoria aron A.Shoara Daniel T.macKeigan Christopher J.Khoury Sladjana Slavkovicl Lisha Lin Danielle Karakas Ziyan Chen Viktor Prifti Zhenze Liu Chuanbin Shen Yuchong Li Cheng Zhang Jiayu Dou Zack Rousseau Jiamin Zhang Tiffany Ni Xi Lei Pingguo Chen Xiaoyu Wu Hamed Shaykhalishahi Samira mubareka Kim AConnelly Haibo Zhang Ori Rotstein Heyu Ni Department of Laboratory medicine and Pathobiology University of TorontoTorontoONCanada Department of Laboratory medicine Keenan Research Centre for Biomedical Science of St.Michael’s HospitalTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Department of Physiology University of TorontoTorontoONCanada CCOA Therapeutics Inc. TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada The State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Laboratory medicine The Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina Advanced Pharmaceutics&Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoONCanada Department of medical microbiology and Infectious Disease Sunnybrook Health Science CentreToronto ONCanada Department of medicine University of TorontoTorontoONCanada Division of Cardiology.St.m.chael's Hospital TorontoONCanada Department of Anesthesiology and Pain medicine and Division of Critical Care medicine University of TorontoTorontoONCanada interdepartmental Division of Critical Care medicine University of TorontoTorontoONCanada Department of Surgery University of Toronto TorontoONCanada.

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health *** cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately *** infection and vaccination utilize the spike protein receptor-binding domain(RBD)of *** found that intravenous injection of recombinant RBD caused significant platelet clearance in *** investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa *** RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−***,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 *** data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and *** newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

关键词： Antibody diagnosis vaccine

Prediction of high thermoelectric performance in the lowdimensional metal halide Cs_(3)Cu_(2)I_(5)

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npj Computational materials 2021年第1期7卷 476-481页

作者： Young-Kwang Jung In Taek Han Yong Churl Kim aron Walsh Department of materials Science and Engineering Yonsei UniversitySeoulSouth Korea Samsung Advanced Institute of Technology(SAIT) Samsung Electronics Materials Research ComplexYoungtongSuwonSouth Korea Department of materials Imperial College LondonLondonUK

metal halides have emerged as a new generation of semiconductors with applications ranging from solar cells to chemical *** assess the thermoelectric potential of Cs_(3)Cu_(2)I_(5),which has a crystal structure formed of zero-dimensional[Cu_(2)I_(5)]3−anionic clusters that are separated by Cs+counter *** find the compound exhibits the characteristics of a phonon-glass electroncrystal with a large imbalance in the conduction of heat and electrons predicted from first-principles transport *** anharmonic phonon–phonon scattering results in short-lived acoustic vibrations and an ultra-low lattice thermal conductivity(m^(−1)K^(−1)).The dispersive conduction band leads to a high electron mobility(>10 cm^(2)V^(−1)s^(−1)).For an n-type crystal at 600 K,a thermoelectric figure-of-merit ZT of 2.6 is found to be accessible,which for a cold source of 300 K corresponds to a thermodynamic heat-to-electricity conversion efficiency of 15%.

关键词： theory phonon crystal

Perovskite synthesizability using graph neural networks

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npj Computational materials 2022年第1期8卷 697-704页

作者： Geun Ho Gu Jidon Jang Juhwan Noh aron Walsh Yousung Jung Department of Chemical and Biomolecular Engineering(BK21 four) KAIST291 Daehak-ro 34141Daejeon305-335South Korea School of Energy Technology Korea Institute of Energy Technology200 Hyuksin-roNaju58330South Korea Department of materials Imperial College LondonLondonSW72AZUK Department of materials Science and Engineering Yonsei UniversitySeoul03722South Korea

Perovskite is an important material type in geophysics and for technologically important ***,the number of synthetic perovskites remains relatively *** accelerate the high-throughput discovery of perovskites,we propose a graph neural network model to assess their *** trained model shows a promising 0.957 out-of-sample true positive rate,significantly improving over empirical rule-based *** validation is established by demonstrating that a significant portion of the virtual crystals that are predicted to be synthesizable have already been indeed synthesized in literature,and those with the lowest synthesizability scores have not been *** previous empirical strategies are mainly applicable to metal oxides,our model is general and capable of predicting the synthesizability across all classes of perovskites,including chalcogenide,halide,and hydride perovskites,as well as *** apply the method to identify synthesizable perovskite candidates for two potential applications,the Li-rich ion conductors and metal halide optical materials that can be tested experimentally.

关键词： methods. perovskite halide

Intrinsic Instability of the Hybrid Halide Perovskite Semiconductor CH3NH3PbI3

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Chinese Physics Letters 2018年第3期35卷 52-57页

作者：张越宇陈时友许朋向红军龚新高 aron Walsh 魏苏淮 Key Laboratory for Computational Physical Sciences(mOE) State Key Laboratory of Surface Physicsand Department of PhysicsFudan UniversityShanghai 200433 Key Laboratory of Polar materials and Devices(mOE) East China Normal UniversityShanghai 200241 Center for Sustainable Chemical Technologies and Department of Chemistry University of BathBath BA2 7AYUK Beijing Computational Science Research Center Beijing 100094

The organic-inorganic hybrid perovskite CH3NH3PbI3 has attracted significant interest for its high performance in converting solar light into electrical power with an efficiency exceeding 20%. Unfortunately, chemical stability is one major challenge in the development of CH3NH3PbI3 solar cells. It was commonly assumed that moisture or oxygen in the environment causes the poor stability of hybrid halide perovskites, however, here we show from the first-principles calculations that the room-temperature tetragonal phase of CH3NH3PbI3 is thermodynamically unstable with respect to the phase separation into CH3NH3I ＋ PbI2, i.e., the disproportionation is exothermic, independent of the humidity or oxygen in the atmosphere. When the structure is distorted to the low-temperature orthorhombie phase, the energetic cost of separation increases, but remains small. Contributions from vibrational and configurational entropy at room temperature have been considered, but the instability of CH3NH3PbI3 is unchanged. When I is replaced by Br or CI, Pb by Sn, or the organic cation CH3NH3 by inorganic Cs, the perovskites become more stable and do not phase-separate spontaneously. Our study highlights that the poor chemical stability is intrinsic to CH3NH3PbI3 and suggests that element-substitution may solve the chemical stability problem in hybrid halide perovskite solar cells.

关键词： NH Pb CH Intrinsic Instability of the Hybrid Halide Perovskite Semiconductor CH3NH3PbI3

Identifying the ground state structures of point defects in solids

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npj Computational materials 2023年第1期9卷 2095-2105页

作者： Irea mosquera-Lois Seán R.Kavanagh aron Walsh David O.Scanlon Thomas Young Centre and Department of Chemistry University College London20 Gordon StreetLondon WC1H 0AJUK Thomas Young Centre and Department of materials Imperial College LondonExhibition RoadLondon SW72AZUK

Point defects are a universal feature of *** identification is addressed by combining experimental measurements with theoretical *** standard modelling approach is,however,prone to missing the ground state atomic configurations associated with energy-lowering reconstructions from the idealised crystallographic *** ground states compromise the accuracy of calculated *** address this issue,we report an approach to navigate the defect configurational landscape using targeted bond distortions and *** of our workflow to eight materials(CdTe,GaAs,Sb_(2)S_(3),Sb_(2)Se_(3),CeO_(2),In_(2)O_(3),ZnO,anatase-TiO_(2))reveals symmetry breaking in each host crystal that is not found via conventional local minimisation *** point defect distortions are classified by the associated physico-chemical *** demonstrate the impact of these defect distortions on derived properties,including formation energies,concentrations and charge transition *** work presents a step forward for quantitative modelling of imperfect solids.

关键词： ground distortion solids

Silicon waveguide cantilever displacement sensor for potential application for on-chip high speed AFm

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Frontiers of Optoelectronics 2018年第1期11卷 53-59页

作者： Peng WANG aron m.chael Chee Yee KWOK School of Electrical Engineering and Telecommunications University of New South Wales Kensington NSW 2052 Australia

This paper reviews an initial achievement of our group toward the development of on-chip parallel high-speed atomic force microscopy（HS-AFm）.A novel AFm approach based on silicon waveguide cantilever displacement sensor is *** displacement sensing approach uniquely allows the use of nano-scale wide cantilever that has a high resonance frequency and low spring constant desired for on-chip parallel *** approach consists of low loss silicon waveguide with nano-gap,highly efficient misalignment tolerant coupler,novel high aspect ratio（HAR）sharp nano-tips that can be integrated with nano-scale wide cantilevers and electrostatically driven nano-cantilever *** simulation results show that the displacement sensor with optical power responsivity of 0.31%/nm and AFm cantilever with resonance frequency of 5.4 mHz and spring constant of 0.21 N/m are achievable with the proposed *** developed silicon waveguide fabrication method enables silicon waveguide with 6 and 7.5 dB/cm transmission loss for TE and Tm modes,respectively,and formation of 13 nm wide nano-gaps between silicon *** coupler demonstrates misalignment tolerance of ±1.8 μm for 5μm spot size lensed fiber and coupling loss of 2.12 dB/facet for standard cleaved single mode fiber without compromising other *** nano-tips with apex radius as small as 2.5 nm and aspect ratio of more than 50 has been enabled by the development of novel HAR nanotip fabrication *** of the HAR tips onto an array of 460 nm wide cantilever beam has also been demonstrated.

关键词： atomic force microscopy (AFm) siliconwaveguide silicon coupler high aspect ratio (HAR) nanotips

Correlation of an ex Vivo model with Clinical Application of an Epigenetic modifier, Inhibiting Tumor Growth and metastasis, in Resistant Cholangiocarcinoma—A Case Study

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Journal of Cancer Therapy 2016年第1期7卷 50-54页

作者： m. A. Nezami aron Gould Simon Geoffrey Bartholomeusz Pacific medical Center of Hope Inc. Fresno CA USA Valley metabolic Imaging (VmI) Fresno CA USA Si RNA Department Experimental Therapeutics MD Anderson Cancer Center Houston TX USA

Bile duct cancer is a rare form of cancer, with approximately 2000 new cases diagnosed in the United States each year. The prognosis of this disease is very grave, especially in the form of intrahepatic (IHCC), as there is no person with stage four who lives for 5 years, and the average prognosis is less than a year, a majority of patients die in less than 6 months despite all therapies. It is suggested that one of the key elements in the disease progression is the intratumoral hypoxia inducible factor one alfa (HIF-1a) as a regulator of malignant behavior and recently described as a new prognostic indicator of IHCC. (9, 10) HIF is a key regulator under the microenvironmental (terrain) influence, and therefore studies of the cell lines in an in vitro environment where there is no hypoxia, usually fail to translate to a clinical outcome in vivo, unless the cells are transfected by full-length HIF-1alpha (fL HIF-1alpha) and dominant-negative HIF-1alpha (dn HIF-1alpha). To overcome this barrier, an ex vivo model is designed at mD Anderson experimental therapeutics where the patient tumor sample is transferred to the mice and treated with drugs, where the tumor can cross talk with the actual terrain and mimic the human stroma where the HIF can be triggered. Results show significant tumor necrosis on the intrahepatic cholangiocacinoma, only after 5 days of exposure to an experimental compound that is known to suppress hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF-1α) through inhibiting protein synthesis. (11, 12) Further this is explored in the same actual patient with terminal diagnosis, and proves itself with promising initial response. Here, we review this method and the clinical perspectives, and suggest this method to be studied in larger trials.

关键词： Cholangiocarcinoma Epigenetic Therapies

Single and bundled carbon nanofibers as ultralightweight and flexible piezoresistive sensors

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npj Flexible Electronics 2020年第1期4卷 82-92页

作者： Debarun Sengupta Ssu-Han Chen aron m.chael Chee Yee Kwok Sean Lim Yutao Pei Ajay Giri Prakash Kottapalli Department of Advanced Production Engineering(APE) Engineering and Technology Institute Groningen(ENTEG)University of Groningen9747 AG GroningenThe Netherlands School of Electrical Engineering&Telecommunications The University of New South WalesSydneyNSW 2052Australia mark Wainwright Analytical Center The University of New South WalesSydneyNSW 2052Australia mIT Sea Grant College Program Massachusetts Institute of Technology(MIT)77 Massachusetts AvenueNW98-151CambridgeMA 02139USA

This work demonstrates the application of electrospun single and bundled carbon nanofibers(CNFs)as piezoresistive sensing elements in flexible and ultralightweight ***,electrical,and nanomechanical characterizations were conducted on the CNFs to understand the effect of the critical synthesis parameter—the pyrolyzation temperature on the morphological,structural,and electrical *** mechanism of conductive path change under the influence of external stress was hypothesized to explain the piezoresistive behavior observed in the CNF ***-static tensile strain characterization of the CNF bundle-based flexible strain sensor showed a linear response with an average gauge factor of 11.14(for tensile strains up to 50%).Furthermore,conductive graphitic domain discontinuity model was invoked to explain the piezoresistivity originating in a single isolated electrospun ***,a single piezoresistive CNF was utilized as a sensing element in an NEmS flow sensor to demonstrate air flow sensing in the range of 5-35 m/s.

关键词： bundle fibers conductive

Intralesional steroid is beneficial in benign refractory esophageal strictures:A meta-analysis

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World Journal of Gastroenterology 2018年第21期24卷 2311-2319页

作者： László Szapáry Benedek Tinusz Nelli Farkas Katalin márta Lajos Szakó Agnes meczker Roland Hágendorn Judit Bajor aron Vincze Zoltan Gyongyi Alexandra mikó Dezso Csupor Péter Hegyi Balint Eross Institute for Translational medicine Medical SchoolUniversity of PécsPécs 7624Hungary Institute of Bioanalysis Medical SchoolUniversity of PécsPécs 7624Hungary Department of Gastroenterology First Department of MedicineMedical SchoolUniversity of PécsPécs 7624Hungary Department of Public Health medicine Medical SchoolUniversity of PécsPécs 7624Hungary Department of Pharmacognosy Faculty of PharmacyUniversity of SzegedSzeged 6720Hungary

AIm To analyze the effect of intralesional steroid injections in addition to endoscopic dilation of benign refractory esophageal *** A comprehensive search was performed in three databases from inception to 10 April 2017 to identify trials, comparing the efficacy of endoscopic dilation to dilation combined with intralesional steroid injections. Following the data extraction, meta-analytical calculations were performed on measures of outcome by the randomeffects method of Der Simonian and Laird. Heterogeneity of the studies was tested by Cochrane's Q and I^2 statistics. Risk of quality and bias was assessed by the Newcastle Ottawa Scale and JADAD assessment *** Eleven articles were identified suitable for analyses, involving 343 patients, 235 cases and 229 controls in total. Four studies used crossover design with 121 subjects enrolled. The periodic dilation index(PDI) was comparable in 4 studies, where the pooled result showed a significant improvement of PDI in the steroid group(mD:-1.12 dilation/month, 95% CI:-1.99 to -0.25 P = 0.012; I^2 = 74.4%). The total number of repeat dilations(TNRD) was comparable in 5 studies and showed a non-significant decrease(mD:-1.17, 95%CI:-0.24-0.05, P = 0.057; I^2 = 0), while the dysphagia score(DS) was comparable in 5 studies and did not improve(SmD: 0.35, 95%CI:-0.38, 1.08, P = 0.351; I^2 = 83.98%) after intralesional steroid *** Intralesional steroid injection increases the time between endoscopic dilations of benign refractory esophageal strictures. However, its potential role needs further research.

关键词： Intralesional steroid meta-analysis Benign refractory esophageal stricture Dilation