13 research outputs found

    Sliding Mode Control with Gain-Scheduled for Magnetic Levitation System

    Get PDF
    This paper presents a study of controlling magnetic levitation object using conventional sliding mode control (CSMC) and sliding mode control (SMC) with gain-scheduled. SMC with gain-scheduled aims to improve the robustness of the control system from disturbance. The CSMC simulation results show that output can follow the set point if there is no interference, but if the disturbance happens then there is overshoot and undershoot of 0.034 mm and 0.07 mm for disturbance 10 ∗ sin

    Sliding Mode Control with Gain-Scheduled for Magnetic Levitation System

    Get PDF
    This paper presents a study of controlling magnetic levitation object using conventional sliding mode control (CSMC) and sliding mode control (SMC) with gain-scheduled. SMC with gain-scheduled aims to improve the robustness of the control system from disturbance. The CSMC simulation results show that output can follow the set point if there is no interference, but if the disturbance happens then there is overshoot and undershoot of 0.034 mm and 0.07 mm for disturbance 10 ∗ sin () and 20 ∗ sin (). Then SMC with gain-scheduled shows excellent performance because the output can follow the reference even if it got disturbance of 10 ∗ sin () and 20 ∗ sin ()

    Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

    Get PDF
    Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic1–4. Vaccines that elicit protective immunity against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that macaque immunization with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052/Alum elicited cross-neutralizing antibody (cross-nAb) responses against batCoVs, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization ID50 titer of 47,216, and protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD also induced SARS-CoV-1 and batCoV cross-nAbs, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV vaccines

    Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

    Get PDF
    Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants

    Integrin-mediated Tyrosine Phosphorylation of Shc in T Cells Is Regulated by Protein Kinase C-dependent Phosphorylations of Lck

    No full text
    Integrin receptor signals are costimulatory for mitogenesis with the T-cell receptor during T-cell activation. A subset of integrin receptors can link to the adapter protein Shc and provide a mitogenic stimulus. Using a combination of genetic and pharmacological approaches, we show herein that integrin signaling to Shc in T cells requires the receptor tyrosine phosphatase CD45, the Src family kinase member Lck, and protein kinase C. Our results suggest a model in which integrin-dependent serine phosphorylation of Lck is the critical step that determines the efficiency of Shc tyrosine phosphorylation in T cells. Serine phosphorylation of Lck is dependent on PKC and is also linked to CD45 dephosphorylation. Mutants of Lck that cannot be phosphorylated on the critical serine residues do not signal efficiently to Shc and have greatly reduced kinase activity. This signaling from integrins to Lck may be an important step in the costimulation with the T-cell receptor during lymphocyte activation
    corecore