Steering Electron-Induced Surface Reaction via a Molecular Assembly Approach.

Electrons not only serve as a "reactant" in redox reactions but also play a role in "catalyzing" some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C-Cl bond in 4,4″-dichloro-1,1':3',1''-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C-Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C-Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.

Selective Cleavage of α-Olefins to Produce Acetylene and Hydrogen.

Acetylene production from mixed α-olefins emerges as a potentially green and energy-efficient approach with significant scientific value in the selective cleavage of C-C bonds. On the Pd(100) surface, it is experimentally revealed that C2 to C4 α-olefins undergo selective thermal cleavage to form surface acetylene and hydrogen. The high selectivity toward acetylene is attributed to the 4-fold hollow sites which are adept at severing the terminal double bonds in α-olefins to produce acetylene. A challenge arises, however, because acetylene tends to stay at the Pd(100) surface. By using the surface alloying methodology with alien Au, the surface Pd d-band center has been successfully shifted away from the Fermi level to release surface-generated acetylene from α-olefins as a gaseous product. Our study actually provides a technological strategy to economically produce acetylene and hydrogen from α-olefins.

Assembling Surface Molecular Sierpinski Triangle Fractals via K+-Invoked Electrostatic Interaction.

Molecular Sierpinski triangles (STs), a family of elegant and well-known fractals, can be prepared on surfaces with atomic precision. Up to date, several kinds of intermolecular interactions such as hydrogen bond, halogen bond, coordination, and even covalent bond have been employed to construct molecular STs on metal surfaces. Herein a series of defect-free molecular STs have been fabricated via electrostatic attraction between potassium cations and electronically polarized chlorine atoms in 4,4″-dichloro-1,1':3',1″-terphenyl (DCTP) molecules on Cu(111) and Ag(111). The electrostatic interaction is confirmed both experimentally by scanning tunneling microscopy and theoretically by density functional theory calculations. These findings illustrate that electrostatic interaction can serve as an efficient driving force to construct molecular fractals, which enriches our toolbox for the bottom-up fabrication of complex functional supramolecular nanostructures.

Analysis of B Cell Receptor Repertoires Reveals Key Signatures of the Systemic B Cell Response after SARS-CoV-2 Infection.

A comprehensive study of the B cell response against SARS-CoV-2 could be significant for understanding the immune response and developing therapeutical antibodies and vaccines. To define the dynamics and characteristics of the antibody repertoire following SARS-CoV-2 infection, we analyzed the mRNA transcripts of immunoglobulin heavy chain (IgH) repertoires of 24 peripheral blood samples collected between 3 and 111 days after symptom onset from 10 COVID-19 patients. Massive clonal expansion of naive B cells with limited somatic hypermutation (SHM) was observed in the second week after symptom onset. The proportion of low-SHM IgG clones strongly correlated with spike-specific IgG antibody titers, highlighting the significant activation of naive B cells in response to a novel virus infection. The antibody isotype switching landscape showed a transient IgA surge in the first week after symptom onset, followed by a sustained IgG elevation that lasted for at least 3 months. SARS-CoV-2 infection elicited poly-germ line reactive antibody responses. Interestingly, 17 different IGHV germ line genes recombined with IGHJ6 showed significant clonal expansion. By comparing the IgH repertoires that we sequenced with the 774 reported SARS-CoV-2-reactive monoclonal antibodies (MAbs), 13 shared spike-specific IgH clusters were found. These shared spike-specific IgH clusters are derived from the same lineage of several recently published neutralizing MAbs, including CC12.1, CC12.3, C102, REGN10977, and 4A8. Furthermore, identical spike-specific IgH sequences were found in different COVID-19 patients, suggesting a highly convergent antibody response to SARS-CoV-2. Our analysis based on sequencing antibody repertoires from different individuals revealed key signatures of the systemic B cell response induced by SARS-CoV-2 infection. IMPORTANCE Although the canonical delineation of serum antibody responses following SARS-CoV-2 infection has been well established, the dynamics of antibody repertoire at the mRNA transcriptional level has not been well understood, especially the correlation between serum antibody titers and the antibody mRNA transcripts. In this study, we analyzed the IgH transcripts and characterized the B cell clonal expansion and differentiation, isotype switching, and somatic hypermutation in COVID-19 patients. This study provided insights at the repertoire level for the B cell response after SARS-CoV-2 infection.

Molecular insight into on-surface chemistry of an organometallic polymer.

A molecular investigation of Cu-elimination and subsequent C-C coupling of DCTP (4,4''-dichloro-1,1':3',1''-terphenyl)-Cu organometallic (OM) polymers on Cu(111) is conducted by scanning tunneling microscopy and spectroscopy, revealing that the Cu adatoms embedded in the DCTP-Cu chains are located at the hollow and bridge sites on the Cu(111) surface. The difference in the catalytic activities of these surface sites leads to stepwise elimination of Cu adatoms in the OM chains. Moreover, the interchain interaction plays an important role in the Cu-elimination process of the DCTP-Cu chains as well. The interchain steric hindrance, on the one hand, induces the formation of Cu-eliminated intermediates that are scarcely observed in other Ullmann coupling systems, and on the other hand, promotes the cooperative Cu-elimination and C-C coupling of the OM segments in neighboring chains. These findings demonstrate the key role of the molecule-substrate and intermolecular interactions in mediating the reaction processes of the extended molecular systems on the surface.

Chemical profiling of Ziziphi spinosae semen using on-line comprehensive two-dimensional liquid chromatography-mass spectrometry based on a novel phthalic anhydride bonded stationary phase.

Ziziphi spinosae semen has been widely used to treat insomnia and anxiety. To profile its chemical components, an online comprehensive two-dimensional liquid chromatography-mass spectrometry was developed. In this two-dimensional liquid chromatography system, a novel phthalic anhydride-bonded stationary phase column was combined with a C18 column. As a result, this new stationary phase exhibited remarkable differences in separation selectivity from C18, achieving a good orthogonality of 83.3%. Moreover, this new stationary phase with weaker hydrophobicity than C18 realized solvent compatibility in the online configuration. Coupled with tandem MS, 154 compounds were identified, including 51 unreported compounds. Compared with one-dimensional liquid chromatography-mass spectrometry, this online two-dimensional liquid chromatography-mass spectrometry system exhibited a much higher resolving power in isomer separation. This work provided an effective separation and characterization method for the material basis of Ziziphi spinosae semen. This strategy provides ideas for the material basis research of other traditional Chinese medicines.

PagERF81 regulates lignin biosynthesis and xylem cell differentiation in poplar.

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.

Massive Loss of Transcription Factors Promotes the Initial Diversification of Placental Mammals.

As one of the most successful group of organisms, mammals occupy a variety of niches on Earth as a result of macroevolution. Transcription factors (TFs), the fundamental regulators of gene expression, may also have evolved. To examine the relationship between TFs and mammalian macroevolution, we analyzed 140,821 de novo-identified TFs and their birth and death histories from 96 mammalian species. Gene tree vs. species tree reconciliation revealed that placental mammals experienced an upsurge in TF losses around 100 million years ago (Mya) and also near the Cretaceous-Paleogene boundary (K-Pg boundary, 66 Mya). Early Euarchontoglires, Laurasiatheria and marsupials appeared between 100 and 95 Mya and underwent initial diversification. The K-Pg boundary was associated with the massive extinction of dinosaurs, which lead to adaptive radiation of mammals. Surprisingly, TF loss decelerated, rather than accelerated, molecular evolutionary rates of their target genes. As the rate of molecular evolution is affected by the mutation rate, the proportion of neutral mutations and the population size, the decrease in molecular evolution may reflect increased functional constraints to survive target genes.

Correction: Zhao, X.W., et al. Dioscin Induces the Apoptosis of Human Cervical Carcinoma HeLa and SiHa Cells Through ROS-mediated DNA Damage, Cell Cycle Arrest and Mitochondrial Signaling Pathways. Molecules 2016, 21, 730.

During the course of a review of our publications, an error in the title paper [...].

Rotating Stall Induced Non-Synchronous Blade Vibration Analysis for an Unshrouded Industrial Centrifugal Compressor.

Rotating stall limits the operating range and stability of the centrifugal compressor and has a significant impact on the lifetime of the impeller blade. This paper investigates the relationship between stall pressure wave and its induced non-synchronous blade vibration, which will be meaningful for stall resonance avoidance at the early design phase. A rotating disc under a time-space varying load condition is first modeled to understand the physics behind stall-induced vibration. Then, experimental work is conducted to verify the model and reveal the mechanism of stall cells evolution process within flow passage and how blade vibrates when suffering such aerodynamic load. The casing mounted pressure sensors are used to capture the low-frequency pressure wave. Strain gauges and tip timing sensors are utilized to monitor the blade vibration. Based on circumferentially distributed pressure sensors and stall parameters identification method, a five stall cells mode is found in this compressor test rig and successfully correlates with the blade non-synchronous vibration. Furthermore, with the help of tip timing measurement, all blades vibration is also evaluated under different operating mass flow rate. Analysis results verify that the proposed model can show the blade forced vibration under stall flow condition. The overall approach presented in this paper is also important for stall vibration and resonance free design with effective experimental verification.

How does 'park and ride' perform? An evaluation using longitudinal data.

The efficiency of park and ride (PnR) lots has not been investigated in serious depth in prior literature. This study examines the effect of various factors on the utilization rate of PnR lots with panel Tobit models. The examined factors consist of land use features, roadway design features, transit ridership, sociodemographic attributes, travel characteristics, policy tools, gasoline prices, and weather conditions. The data is drawn from PnR lots in King County, Washington. Results show that: (1) degree of mixed land use, road density, employment density, percentages of people aged between 18 and 34 and people over 65, the percentage of white people, the percentage of poor people, and transit ridership are positively associated with the utilization rate of PnR lots; (2) the percentage of drive lanes in total roadway miles, the percentage of males, and the mode share percentage of driving are negatively correlated with the utilization rate of PnR lots; (3) various policy interventions, including countermeasures for preserving transit after the economic recession, congestion reduction charge, and bus-rail integration, are all positively correlated with the utilization rate of PnR lots. Contextualized to US cities, PnR is a practical way to attract bus riders, especially young adults, senior citizens, and low-income people to public transit. Dense urban development is encouraged for the full utilization of PnR lots. Additionally, the integration between bus and rail appears to be an effective policy tool to promote PnR utilization.

A Novel Tumor-Suppressor, CDH18, Inhibits Glioma Cell Invasiveness Via UQCRC2 and Correlates with the Prognosis of Glioma Patients.

BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.

Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway.

Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca(2+) levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway.

Fabrication and Composition of MA1-y FA y SnI3-x Br x Thin Films for Lead-Free Perovskite Solar Cells.

Perovskite solar cells have gained significant attention in recent years due to their lightweight nature, flexibility, and ability to generate power even in weak-light conditions. Despite these advantages, the current mainstream perovskite solar cells contain lead, raising concerns about their environmental and human health effects. Tin is expected to be a substitutional element for lead; however, tin-based perovskite solar cells currently have low power conversion efficiency. Altering the composition of the perovskite is crucial for enhancing its performance. In this study, perovskite solar cells with mixed MA/FA and I/Br components were designed and fabricated based on the calculation of the tolerance factor. The crystallinity and band gap of perovskite thin films were manipulated by changing the compositions of anions and cations. A suitable composition ratio for perovskite solar cells was proposed and discussed.

Study on the damage and seepage characteristics of water-saturated coal by microwave cycling.

To investigate the extent of damage and seepage characteristics of water-saturated coal samples after subjecting them to microwave cycling. The microwave equipment was used to process the coal samples by microwave cycling. The non-contact digital image processing technology and acoustic emission system were used to carry out the triaxial loading experimental study of the coal samples to obtain the mechanical parameter characteristics, energy evolution pattern, acoustic emission information and permeability characteristics of coal samples under different microwave cycle times. The results of the study show that: With the increase in the number of microwave cycles, dense grid-loaded cracks gradually appeared on the surface of the coal samples, the triaxial partial stresses of the coal samples decreased, and the strains also decreased, and the modulus of elasticity and Poisson's ratio also decreased; In the densification stage stage, the dissipated energy is higher than the elastic energy, and as the elastic stage proceeds, the elastic energy gradually reverses to exceed the dissipated energy, and the total energy and elastic energy of the coal samples decrease with the increase in the number of cycles, and the dissipated energy rises; Coal samples produce a large number of fissures due to the increase in the number of microwave cycles, the more frequent the fissure activity during the loading process, the acoustic emission amplitude and ringing count scattering points all become dense with the increase in the number of cycles, and the data increase; Initial permeability, destructive permeability and average permeability were all increased, microwave treatment has a better effect of permeability enhancement, the permeability of the treated coal samples was changed from low permeability to medium permeability, and the permeability enhancement was the largest in 6 cycles, and the permeability was increased by 7.18 times. This article explores the damage condition of water-saturated coal samples under microwave cycling treatment. Then, it explores the effect of microwave cycling on the permeability enhancement of the coal body, which provides a new method for exploring the gas permeability enhancement and extraction of low-permeability coal samples underground.

PermuteDDS: a permutable feature fusion network for drug-drug synergy prediction.

MOTIVATION: Drug combination therapies have shown promise in clinical cancer treatments. However, it is hard to experimentally identify all drug combinations for synergistic interaction even with high-throughput screening due to the vast space of potential combinations. Although a number of computational methods for drug synergy prediction have proven successful in narrowing down this space, fusing drug pairs and cell line features effectively still lacks study, hindering current algorithms from understanding the complex interaction between drugs and cell lines. RESULTS: In this paper, we proposed a Permutable feature fusion network for Drug-Drug Synergy prediction, named PermuteDDS. PermuteDDS takes multiple representations of drugs and cell lines as input and employs a permutable fusion mechanism to combine drug and cell line features. In experiments, PermuteDDS exhibits state-of-the-art performance on two benchmark data sets. Additionally, the results on independent test set grouped by different tissues reveal that PermuteDDS has good generalization performance. We believed that PermuteDDS is an effective and valuable tool for identifying synergistic drug combinations. It is publicly available at https://github.com/littlewei-lazy/PermuteDDS . SCIENTIFIC CONTRIBUTION: First, this paper proposes a permutable feature fusion network for predicting drug synergy termed PermuteDDS, which extract diverse information from multiple drug representations and cell line representations. Second, the permutable fusion mechanism combine the drug and cell line features by integrating information of different channels, enabling the utilization of complex relationships between drugs and cell lines. Third, comparative and ablation experiments provide evidence of the efficacy of PermuteDDS in predicting drug-drug synergy.

The Chinese herbal prescription JZ-1 promotes extracellular vesicle production and protects against herpes simplex virus type 2 infection in vitro.

Objective: Genital herpes, primarily caused by HSV-2 infection, remains a widespread sexually transmitted ailment. Extracellular vesicles play a pivotal role in host-virus confrontation. Recent research underscores the influence of Chinese herbal prescriptions on extracellular vesicle production and composition. This study aims to probe the impact of JieZe-1 (JZ-1) on extracellular vesicle components, elucidating its mechanisms against HSV-2 infection via extracellular vesicles. Methods: The JZ-1's anti-HSV-2 effects were assessed using CCK-8 assay. Extracellular vesicles were precisely isolated utilizing ultracentrifugation and subsequently characterized through TEM, NTA, and Western Blot analyses. The anti-HSV-2 activity of extracellular vesicles was gauged using CCK-8, Western Blot, and immunofluorescence. Additionally, high-throughput sequencing was employed to detect miRNAs from extracellular vesicles, unraveling the potential antiviral mechanisms of JZ-1. Results: Antiviral efficacy of JZ-1 was shown in VK2/E6E7, HeLa, and Vero cells. The samples extracted from cell supernatant by ultracentrifugation were identified as extracellular vesicles. In VK2/E6E7 cells, extracellular vesicles from JZ-1 group enhanced cell survival rates and diminished the expression of intracellular viral protein gD, contrasting with the inert effect of control group vesicles. Extracellular vesicles from JZ-1 treated Vero cells demonstrated a weaker yet discernible anti-HSV-2 effect. Conversely, extracellular vesicles of HeLa cells exhibited no anti-HSV-2 effect from either group. High-throughput sequencing of VK2/E6E7 cell extracellular vesicles unveiled significant upregulation of miRNA-101, miRNA-29a, miRNA-29b, miRNA-29c, and miRNA-637 in JZ-1 group vesicles. KEGG pathway analysis suggested that these miRNAs may inhibit PI3K/AKT/mTOR signaling pathway and induce autophagy of host cells to protect against HSV-2. Western blot confirmed the induction of autophagy and inhibition of AKT/mTOR in VK2/E6E7 cells with JZ-1 group extracellular vesicles treatment. Conclusion: JZ-1 had an anti-HSV-2 efficacy. After JZ-1 stimulation, VK2/E6E7 cells secreted extracellular vesicles which protect host cells from HSV-2 infection. High-throughput sequencing showed that these extracellular vesicles contained a large number of miRNAs targeting PI3K/AKT/mTOR pathway. JZ-1 group extracellular vesicles could inhibit the activation of AKT/mTOR pathway and induce the host cells autophagy.

PhenoID, a language model normalizer of physical examinations from genetics clinical notes.

Background: Phenotypes identified during dysmorphology physical examinations are critical to genetic diagnosis and nearly universally documented as free-text in the electronic health record (EHR). Variation in how phenotypes are recorded in free-text makes large-scale computational analysis extremely challenging. Existing natural language processing (NLP) approaches to address phenotype extraction are trained largely on the biomedical literature or on case vignettes rather than actual EHR data. Methods: We implemented a tailored system at the Children's Hospital of Philadelpia that allows clinicians to document dysmorphology physical exam findings. From the underlying data, we manually annotated a corpus of 3136 organ system observations using the Human Phenotype Ontology (HPO). We provide this corpus publicly. We trained a transformer based NLP system to identify HPO terms from exam observations. The pipeline includes an extractor, which identifies tokens in the sentence expected to contain an HPO term, and a normalizer, which uses those tokens together with the original observation to determine the specific term mentioned. Findings: We find that our labeler and normalizer NLP pipeline, which we call PhenoID, achieves state-of-the-art performance for the dysmorphology physical exam phenotype extraction task. PhenoID's performance on the test set was 0.717, compared to the nearest baseline system (Pheno-Tagger) performance of 0.633. An analysis of our system's normalization errors shows possible imperfections in the HPO terminology itself but also reveals a lack of semantic understanding by our transformer models. Interpretation: Transformers-based NLP models are a promising approach to genetic phenotype extraction and, with recent development of larger pre-trained causal language models, may improve semantic understanding in the future. We believe our results also have direct applicability to more general extraction of medical signs and symptoms. Funding: US National Institutes of Health.

Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

Adaptive method of dim small object detection with heavy clutter.

This paper investigates an adaptive method of dim small target detection in infrared images with a complex background. We analyze in depth the characteristics of the background, the target, and the noise in the gray intensity, space and frequency domain of the images. The modified top-hat transformation using interrelated structuring elements is adopted to adaptively detect the darker and the brighter targets and greatly suppress the cluttered background. Lateral pattern inhibition enhances the local contrast ratio and simultaneously identifies the targets of interest. The automatic threshold is used to enhance real dim targets in the cluttered background. A simulation based on the proposed algorithm is carried out and the results prove that the algorithm is effective and valid.