Background: Plagiocephaly, wherein infants' head exhibits a diagonal asymmetry, is currently diagnosed based on physicians' subjective judgment. Discrepancies between physician and parent perspectives may result in dissatisfaction with treatment outcomes. This problem highlights the need for an objective assessment system aligning with physician-made clinical diagnoses.
View Article and Find Full Text PDFUnlabelled: Understanding how immune history influences influenza immunity is essential for developing effective vaccines and therapeutic strategies. This study examines the antigenic imprinting of influenza hemagglutinin (HA) and neuraminidase (NA) using a mouse model with sequential infections by H1N1 virus strains exhibiting substantial antigenic differences in HA. In our pre-2009 influenza infection model, we observed that mice with more extensive infection histories produced higher levels of functional NA-inhibiting antibodies (NAI).
View Article and Find Full Text PDFCurrent prophylactic human immunodeficiency virus 1 (HIV-1) vaccine research aims to elicit broadly neutralizing antibodies (bnAbs). Membrane-proximal external region (MPER)-targeting bnAbs, such as 10E8, provide exceptionally broad neutralization, but some are autoreactive. Here, we generated humanized B cell antigen receptor knock-in mouse models to test whether a series of germline-targeting immunogens could drive MPER-specific precursors toward bnAbs.
View Article and Find Full Text PDFA key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display.
View Article and Find Full Text PDFSeasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry-based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC cellular antiviral activity against several influenza A group 1 strains.
View Article and Find Full Text PDFThe multi-chiplet technique is expected to be a promising solution to achieve high-density system integration with low power consumption and high usage ratio. This technique can be integrated with a glass interposer to accomplish a competitive low fabrication cost compared with the silicon-based interposer architecture. In this study, process-oriented stress simulation is performed by the element activation and deactivation technique in finite element analysis architecture.
View Article and Find Full Text PDFACS Appl Mater Interfaces
August 2023
In this study, a morphological diagram was constructed for quantitatively predicting various modes of surface instabilities caused by the dynamic interfacial release of strain in initially flat bilayer composites comprising an elastomer and a capping layer. Theory, experiment, and simulation were combined to produce the diagram, which enables systematic generation of the following instability patterns: wrinkle, fold, period-double, delamination, and coexisting patterns. The pattern that forms is most strongly affected by three experimental parameters: the elastic modulus of the elastomer, the elastic modulus of the capping layer, and the thickness of the capping layer.
View Article and Find Full Text PDFInspired by knobby starfish, this work demonstrates a bottom-up approach for fabricating a calcite single-crystal (CSC) with a diamond structure by exploiting the self-assembly of the block copolymer and corresponding templated synthesis. Similar to the knobby starfish, the diamond structure of the CSC gives rise to a brittle-to-ductile transition. Most interestingly, the diamond-structured CSC fabricated exhibits exceptional specific energy absorption and strength with lightweight character superior to natural materials and artificial counterparts from a top-down approach due to the nanosized effect.
View Article and Find Full Text PDFHumanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing.
View Article and Find Full Text PDFIn glass interposer architecture and its assembly process, the mechanical responses of interposer structure under thermocompression process-induced thermal loading and generated shrinkage of molding material are regarded as a major reliability issue. Thousands of metal-filled via are involved in glass interposers and are regarded as a potential risk that can lead to cracking and the failure of an entire vehicle. In this study, a finite element-based submodeling approach is demonstrated to overcome the complexity of modeling and the relevant convergence issue of interposer architecture.
View Article and Find Full Text PDFInspired by Mantis shrimp, this work aims to suggest a bottom-up approach for the fabrication of nanonetwork hydroxyapatite (HAp) thin film using self-assembled polystyrene--polydimethylsiloxane (PS--PDMS) block copolymer (BCP) with a diamond nanostructure as a template for templated sol-gel reaction. By introducing poly(vinylpyrrolidone) (PVP) into precursors of calcium nitrate tetrahydrate and triethyl phosphite, which limits the growth of forming HAp nanoparticles, well-ordered nanonetwork HAp thin film can be fabricated. Based on nanoindentation results, the well-ordered nanonetwork HAp shows high energy dissipation compared to the intrinsic HAp.
View Article and Find Full Text PDFAntigenic imprinting, which describes the bias of the antibody response due to previous immune history, can influence vaccine effectiveness. While this phenomenon has been reported for viruses such as influenza, there is little understanding of how prior immune history affects the antibody response to SARS-CoV-2. This study provides evidence for antigenic imprinting through immunization with two , the subgenus that includes SARS-CoV-2.
View Article and Find Full Text PDFThe potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site.
View Article and Find Full Text PDFUnlabelled: The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site.
View Article and Find Full Text PDFCombinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus.
View Article and Find Full Text PDFStress-induced performance change in electron packaging architecture is a major concern when the keep-out zone (KOZ) and corresponding integration density of interconnect systems and transistor devices are considered. In this study, a finite element analysis (FEA)-based submodeling approach is demonstrated to analyze the stress-affected zone of through-silicon via (TSV) and its influences on a planar metal oxide semiconductor field transistor (MOSFET) device. The feasibility of the widely adopted analytical solution for TSV stress-affected zone estimation, Lamé radial stress solution, is investigated and compared with the FEA-based submodeling approach.
View Article and Find Full Text PDFNeutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of the spike protein of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective against recent variants of concern. RBS residues Glu, Lys, and Asn are mutated in variants first described in South Africa (B.1.
View Article and Find Full Text PDFIt is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD.
View Article and Find Full Text PDFCoronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses.
View Article and Find Full Text PDFHerein, we aim to develop a facile method for the fabrication of mechanical metamaterials from templated polymerization of thermosets including phenolic and epoxy resins using self-assembled block copolymer, polystyrene-polydimethylsiloxane with tripod network (gyroid), and tetrapod network (diamond) structures, as templates. Nanoindentation studies on the nanonetwork thermosets fabricated reveal enhanced energy dissipation from intrinsic brittle thermosets due to the deliberate structuring; the calculated energy dissipation for gyroid phenolic resins is 0.23 nJ whereas the one with diamond structure gives a value of 0.
View Article and Find Full Text PDFIncessant antigenic evolution enables the persistence and spread of influenza virus in the human population. As the principal target of the immune response, the hemagglutinin (HA) surface antigen on influenza viruses continuously acquires and replaces N-linked glycosylation sites to shield immunogenic protein epitopes using host-derived glycans. Anti-glycan antibodies, such as 2G12, target the HIV-1 envelope protein (Env), which is even more extensively glycosylated and contains under-processed oligomannose-type clusters on its dense glycan shield.
View Article and Find Full Text PDFThe protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.
View Article and Find Full Text PDFCoronaviruses have caused several epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Some prophylactic vaccines and therapeutic antibodies have already showed striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses.
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