ABSTRACT
Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have contributed to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMVs) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant MCMV vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMVS). In this study, we show that the MCMVS elicits a robust and lasting protection in young and aged mice. Notably, spike-specific humoral and cellular immunity was not only maintained but also even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMVS conferred rapid virus clearance upon challenge. Moreover, MCMVS vaccination controlled two variants of concern (VOCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19.
Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Mice , COVID-19 Vaccines/immunology , COVID-19/prevention & control , COVID-19/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Viral/immunology , Antibodies, Viral/blood , Muromegalovirus/immunology , Muromegalovirus/genetics , Female , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Mice, Inbred BALB C , Humans , Genetic Vectors , Immunity, Cellular , Immunity, Humoral , Disease Models, AnimalABSTRACT
BACKGROUND: Morning blood pressure surge (MBPS) has been recognized as an independent predictor of cardiovascular disease events. Psychological distress, including anxiety, depression, and perceived stress, and behavioral risk factors, such as poor sleep quality, have been associated with increased MBPS. Elevations in sympathetic activity induced by forced awakening may also contribute to further increases in MBPS. Yet, no examination of the interrelationships among psychological distress, sleep quality, awakening mode (natural vs. forced awakenings), and MBPS has been undertaken. OBJECTIVE: This pilot study aimed: (1) to examine if MBPS differs by awakening mode and (2) to investigate whether psychological distress is associated with MBPS difference between natural and forced awakenings, independent of sleep quality. METHODS: Thirty-two healthy adults were included in this cross-sectional study. Blood pressure was measured using a beat-to-beat blood pressure monitor over two nights, consisting of one night of natural awakening and one night of forced awakening. Psychological distress and sleep quality were assessed using questionnaires. We conducted paired t-tests (aim 1) and multiple linear regressions (aim 2). RESULTS: MBPS was significantly greater during forced awakening compared with natural awakening. In addition, the MBPS difference between natural and forced awakenings was significantly greater in participants with higher anxiety levels, independent of sleep quality. CONCLUSION: We found that augmentation of MBPS by forced awakening was significantly greater in individuals who reported higher anxiety levels. Additional research is needed to examine the potential impacts of forced awakening and anxiety on MBPS in a larger sample of individuals at risk for cardiovascular disease.
ABSTRACT
BACKGROUND: Poor sleep quality can cause an increase in morning blood pressure surge (MBPS), an independent risk factor of cardiovascular disease (CVD) events. Awakening induced by external factors such as alarm clocks, may also contribute to increased MBPS. OBJECTIVES: To (1) compare the MBPS and sleep quality parameters between natural and forced awakenings and (2) examine the potential impact of forced awakening on MBPS, independent of sleep quality. METHODS: Thirty-two healthy adults participated in this pilot study, which included one night of natural awakening and one night of forced awakening (i.e., sleep was interrupted by an alarm after five hours). Objective and self-reported sleep quality parameters were measured using a multisensory wristband and sleep diaries, respectively, and beat-to-beat blood pressure variability was assessed using a continuous blood pressure monitor. Analyses included a paired t-test (objective 1) and linear mixed models (objective 2). RESULTS: Participants predominantly consisted of young, healthy, and highly educated Asian adults. During the night of sleep with forced awakening, significantly higher MBPS, lower objective wakefulness after sleep onset, and lower self-reported sleep latency were observed, compared to the night with natural awakening. Forced awakening was significantly associated with increased MBPS after controlling for age, sex, mean arterial pressure, and sleep quality. CONCLUSIONS: Forced awakening may significantly increase MBPS, consequently heightening the risk of CVD events. Study findings should be validated in a larger sample. Further research is also warranted to examine the impact of forced awakening on MBPS in individuals with CVD.
ABSTRACT
STUDY OBJECTIVE: Intraoperative electroencephalogram (EEG) patterns associated with postoperative delirium (POD) development have been studied, but the differences in EEG recordings between sevoflurane- and desflurane-induced anesthesia have not been clarified. We aimed to distinguish the EEG characteristics of sevoflurane and desflurane in relation to POD development. DESIGN AND PATIENTS: We collected frontal four-channel EEG data during the maintenance of anesthesia from 148 elderly patients who received sevoflurane (n = 77) or desflurane (n = 71); 30 patients were diagnosed with delirium postoperatively. The patients were divided into four subgroups based on anesthetics and delirium status: sevoflurane delirium (n = 17), sevoflurane non-delirium (n = 60), desflurane delirium (n = 13), and desflurane non-delirium (n = 58). We compared spectral power, coherence, and pairwise phase consistency (PPC) between sevoflurane and desflurane, and between non-delirium and delirium groups for each anesthetic. MAIN RESULTS: In patients without POD, the sevoflurane non-delirium group exhibited higher EEG spectral power across 8.5-35 Hz (99.5% CI bootstrap analysis) and higher PPC from alpha to gamma bands (p < 0.005) compared to the desflurane non-delirium group. Conversely, in patients with POD, no significant EEG differences were observed between the sevoflurane and desflurane delirium groups. For the sevoflurane-induced patients, the sevoflurane delirium group had significantly lower power within 7.5-31.5 Hz (99.5% CI bootstrap analysis), reduced coherence over 8.9-23.8 Hz (99.5% CI bootstrap analysis), and lower PPC values in the alpha band (p < 0.005) compared with the sevoflurane non-delirium group. For the desflurane-induced patients, there were no significant differences in the EEG patterns between delirium and non-delirium groups. CONCLUSIONS: In normal patients without POD, sevoflurane demonstrates a higher power spectrum and prefrontal connectivity than desflurane. Furthermore, reduced frontal alpha power, coherence, and connectivity of intraoperative EEG could be associated with an increased risk of POD. These intraoperative EEG characteristics associated with POD are more noticeable in sevoflurane-induced anesthesia than in desflurane-induced anesthesia.
Subject(s)
Anesthetics, Inhalation , Emergence Delirium , Isoflurane , Methyl Ethers , Humans , Aged , Sevoflurane/adverse effects , Desflurane/adverse effects , Anesthetics, Inhalation/adverse effects , Emergence Delirium/chemically induced , Isoflurane/adverse effects , Methyl Ethers/adverse effects , ElectroencephalographyABSTRACT
To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a ß-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known sites of murine cytomegalovirus latency. Whereas murine cytomegalovirus gene transcription in PDGFRα-positive fibroblastic cells is almost completely silenced at 5 months post-infection, these cells give rise to reactivated virus ex vivo, arguing that they support latent murine cytomegalovirus infection. Notably, PDGFRα-positive fibroblastic cells also support productive virus replication during primary murine cytomegalovirus infection. Mechanistically, Stat1-deficiency promotes lytic infection but abolishes latent persistence of murine cytomegalovirus in PDGFRα-positive fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic murine cytomegalovirus replication and a reservoir of latent murine cytomegalovirus in vivo and STAT1 is required for murine cytomegalovirus latent persistence in vivo.
Subject(s)
Cytomegalovirus Infections , Muromegalovirus , Animals , Mice , Cytomegalovirus/genetics , Virus Latency/genetics , Receptor, Platelet-Derived Growth Factor alpha , Virus Replication , Fibroblasts , STAT1 Transcription Factor/geneticsABSTRACT
Vaccines are central to controlling the coronavirus disease 2019 (COVID-19) pandemic but the durability of protection is limited for currently approved COVID-19 vaccines. Further, the emergence of variants of concern (VoCs) that evade immune recognition has reduced vaccine effectiveness, compounding the problem. Here, we show that a single dose of a murine cytomegalovirus (MCMV)-based vaccine, which expresses the spike (S) protein of the virus circulating early in the pandemic (MCMVS), protects highly susceptible K18-hACE2 mice from clinical symptoms and death upon challenge with a lethal dose of D614G SARS-CoV-2. Moreover, MCMVS vaccination controlled two immune-evading VoCs, the Beta (B.1.135) and the Omicron (BA.1) variants in BALB/c mice, and S-specific immunity was maintained for at least 5 months after immunization, where neutralizing titers against all tested VoCs were higher at 5-months than at 1-month post-vaccination. Thus, cytomegalovirus (CMV)-based vector vaccines might allow for long-term protection against COVID-19.
ABSTRACT
SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96-100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Neutralization Tests , Antibodies, Viral , COVID-19 Vaccines , RNA, Messenger , Ad26COVS1 , BNT162 Vaccine , COVID-19/prevention & control , ChAdOx1 nCoV-19 , VaccinationABSTRACT
Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8+ T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8+ T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8+ effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8+ T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.
Subject(s)
COVID-19 , Epitopes, T-Lymphocyte , Animals , Antibodies, Neutralizing , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , Disease Models, Animal , Immunologic Memory , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Vaccines, SyntheticABSTRACT
Recent emergence of SARS-CoV-1 variants demonstrates the potential of this virus for targeted evolution, despite its overall genomic stability. Here we show the dynamics and the mechanisms behind the rapid adaptation of SARS-CoV-2 to growth in Vero E6 cells. The selective advantage for growth in Vero E6 cells is due to increased cleavage efficiency by cathepsins at the mutated S1/S2 site. S1/S2 site also constitutes a heparan sulfate (HS) binding motif that influenced virus growth in Vero E6 cells, but HS antagonist did not inhibit virus adaptation in these cells. The entry of Vero E6-adapted virus into human cells is defective because the mutated spike variants are poorly processed by furin or TMPRSS2. Minor subpopulation that lack the furin cleavage motif in the spike protein rapidly become dominant upon passaging through Vero E6 cells, but wild type sequences are maintained at low percentage in the virus swarm and mediate a rapid reverse adaptation if the virus is passaged again on TMPRSS2+ human cells. Our data show that the spike protein of SARS-CoV-2 can rapidly adapt itself to available proteases and argue for deep sequence surveillance to identify the emergence of novel variants. IMPORTANCE Recently emerging SARS-CoV-2 variants B.1.1.7 (alpha variant), B.1.617.2 (delta variant), and B.1.1.529 (omicron variant) harbor spike mutations and have been linked to increased virus pathogenesis. The emergence of these novel variants highlights coronavirus adaptation and evolution potential, despite the stable consensus genotype of clinical isolates. We show that subdominant variants maintained in the virus population enable the virus to rapidly adapt to selection pressure. Although these adaptations lead to genotype change, the change is not absolute and genomes with original genotype are maintained in the virus swarm. Thus, our results imply that the relative stability of SARS-CoV-2 in numerous independent clinical isolates belies its potential for rapid adaptation to new conditions.
Subject(s)
COVID-19/metabolism , Furin/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Adaptation, Physiological , Animals , COVID-19/genetics , COVID-19/virology , Chlorocebus aethiops , Cytopathogenic Effect, Viral , Furin/genetics , HEK293 Cells , High-Throughput Nucleotide Sequencing , Humans , Mutation , SARS-CoV-2/genetics , Serine Endopeptidases/genetics , Spike Glycoprotein, Coronavirus/genetics , Vero Cells , Virus ReplicationABSTRACT
Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a ß-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of severe acute respiratory syndrome coronavirus 2 (MCMVS). A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA-vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to the effects of memory T cells. Conclusively, we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.
Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Immunity, Humoral , Influenza A virus/immunology , Influenza Vaccines/immunology , Orthomyxoviridae Infections/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/virology , Chlorocebus aethiops , Cytomegalovirus/immunology , Dogs , Female , HEK293 Cells , Humans , Immunity, Cellular , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Orthomyxoviridae Infections/virology , Vero CellsABSTRACT
Forests are critically important for the provision of ecosystem services. The Sacramento Mountains of New Mexico, USA, are a hotspot for conservation management and the Mescalero Apache Tribe's homeland. The multiple ecosystem services and functions and its high vulnerability to changes in climate conditions make their forests of ecological, cultural, and social importance. We used data from the Mescalero Apache Tribal Lands (MATL) Continuous Forest Inventory over 30 yr to analyze changes in the structure and composition of ecosystems as well as trends in ecosystem services. Many provisioning, regulating, cultural, and supporting services were shared among the MATL ecosystems and were tied to foundational species dominance, which could serve as a reliable indicator of ecosystem functioning. Our analysis indicates that the MATL are in an ongoing transition from conifer forests to woodlands with declines in two foundation species, quaking aspen and ponderosa pine, linked to past forest management and changing climate. In addition, we detected a decrease in species richness and tree size variability, amplifying the risk of forest loss in a rapid climatic change. Continuous permanent plots located on a dense grid (1 × 1 km) such as the ones monitored by the Bureau of Indian Affairs are the most detailed data available to estimate forests multiresource transitions over time. Native lands across the USA could serve as the leading edge of detecting decadal-scale forest changes and tracking climate impacts.
Subject(s)
Ecosystem , Tracheophyta , Climate Change , Forests , TreesABSTRACT
The SARS-CoV-2 pandemic is a major global threat that sparked global research efforts. Pre-clinical and biochemical SARS-CoV-2 studies firstly rely on cell culture experiments where the importance of choosing an appropriate cell culture model is often underestimated. We here present a bottom-up approach to identify suitable permissive cancer cell lines for drug screening and virus research. Human cancer cell lines were screened for the SARS-CoV-2 cellular entry factors ACE2 and TMPRSS2 based on RNA-seq data of the Cancer Cell Line Encyclopedia (CCLE). However, experimentally testing permissiveness towards SARS-CoV-2 infection, we found limited correlation between receptor expression and permissiveness. This underlines that permissiveness of cells towards viral infection is determined not only by the presence of entry receptors but is defined by the availability of cellular resources, intrinsic immunity, and apoptosis. Aside from established cell culture infection models CACO-2 and CALU-3, three highly permissive human cell lines, colon cancer cell lines CL-14 and CL-40 and the breast cancer cell line CAL-51 and several low permissive cell lines were identified. Cell lines were characterised in more detail offering a broader choice of non-overexpression in vitro infection models to the scientific community. For some cell lines a truncated ACE2 mRNA and missense variants in TMPRSS2 might hint at disturbed host susceptibility towards viral entry.
Subject(s)
COVID-19/virology , Receptors, Virus , SARS-CoV-2/physiology , Virus Internalization , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Cell Line, Tumor , Humans , Receptors, Virus/genetics , Receptors, Virus/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolismABSTRACT
BACKGROUND: Type II (customer-on-worker) workplace violence (WPV) against nurses and its underreporting are ongoing safety and health challenges in health care. The COVID-19 pandemic has strained patients and nurses and, in turn, may have increased WPV. The purpose of this cross-sectional study was to describe and compare a sample of nurses' reported prevalence of Type II WPV and their reporting of these events during the pandemic. METHODS: Data from an online survey of registered nurses (N = 373) working in hospitals were included. Prevalence was calculated for physical violence and verbal abuse, and their reporting of these events, including the experience of violence between nurses who did and did not care for patients with COVID-19. FINDINGS: Overall, 44.4% and 67.8% of the nurses reported experiencing physical violence and verbal abuse, respectively, between February and May/June 2020. Nurses who provided care for patients with COVID-19 experienced more physical violence (adjusted odds ratio [aOR] = 2.18, 95% confidence interval [CI] = [1.30, 3.67]) and verbal abuse (aOR = 2.10, 95% CI = [1.22, 3.61]) than nurses who did not care for these patients. One in 10 nurses felt reporting the incident was more difficult during the pandemic. CONCLUSION/APPLICATION TO PRACTICE: A significant proportion of nurses who cared for patients with COVID-19 experienced more physical violence and verbal abuse, and more difficulty in reporting to management. As the pandemic continues, health care organizations need to recognize that workers may be at an elevated risk for experiencing WPV and may be less likely to report, resulting in an urgent need for prevention efforts on their part.
ABSTRACT
The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Šresolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.
Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , COVID-19/virology , Humans , Mutation/genetics , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Protein Domains/genetics , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
When thickness-dependent carrier mobility is coupled with Thomas-Fermi screening and interlayer resistance effects in two-dimensional (2D) multilayer materials, a conducting channel migrates from the bottom surface to the top surface under electrostatic bias conditions. However, various factors including (i) insufficient carrier density, (ii) atomically thin material thickness, and (iii) numerous oxide traps/defects considerably limit our deep understanding of the carrier transport mechanism in 2D multilayer materials. Herein, we report the restricted conducting channel migration in 2D multilayer ReS2 after a constant voltage stress of gate dielectrics is applied. At a given gate bias condition, a gradual increase in the drain bias enables a sensitive change in the interlayer resistance of ReS2, leading to a modification of the shape of the transconductance curves, and consequently, demonstrates the conducting channel migration along the thickness of ReS2 before the stress. Meanwhile, this distinct conduction feature disappears after stress, indicating the formation of additional oxide trap sites inside the gate dielectrics that degrade the carrier mobility and eventually restrict the channel migration. Our theoretical and experimental study based on the resistor network model and Thomas-Fermi charge screening theory provides further insights into the origins of channel migration and restriction in 2D multilayer devices.
ABSTRACT
COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a new recently emerged sarbecovirus. This virus uses the human ACE2 enzyme as receptor for cell entry, recognizing it with the receptor binding domain (RBD) of the S1 subunit of the viral spike protein. We present the use of phage display to select anti-SARS-CoV-2 spike antibodies from the human naïve antibody gene libraries HAL9/10 and subsequent identification of 309 unique fully human antibodies against S1. 17 antibodies are binding to the RBD, showing inhibition of spike binding to cells expressing ACE2 as scFv-Fc and neutralize active SARS-CoV-2 virus infection of VeroE6 cells. The antibody STE73-2E9 is showing neutralization of active SARS-CoV-2 as IgG and is binding to the ACE2-RBD interface. Thus, universal libraries from healthy human donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovering patients in a pandemic situation.
Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/genetics , Antibodies, Viral/genetics , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/chemistry , Animals , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/isolation & purification , Antibody Affinity , COVID-19/epidemiology , Cell Line , Chlorocebus aethiops , Gene Library , Healthy Volunteers , Host Microbial Interactions/immunology , Humans , Immunoglobulin G/genetics , Immunoglobulin G/isolation & purification , Models, Molecular , Mutation , Neutralization Tests , Pandemics , Peptide Library , Protein Interaction Domains and Motifs , Recombinant Proteins/genetics , Recombinant Proteins/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Vero CellsABSTRACT
Hot carrier injection (HCI), occurring when the horizontal electric field is strongly applied, usually affects the degradation of nanoelectronic devices. In addition, metal contacts play a significant role in nanoelectronic devices. In this study, Schottky contacts in multilayer tungsten diselenide (WSe2) field-effect transistors (FETs) by hot carrier injection (HCI), occurring when a high drain voltage is applied, is investigated. A small number of hot carriers with high energy reduces the Schottky barrier height and improves the performance of FETs effectively rather than damaging the channel. Thermal annealing at the end of the fabrication process increases device performance by causing interfacial reactions of the source/drain electrodes. HCI causes a significant enhancement in the local asymmetry, especially in the subthreshold region. The subthreshold swing (SS) of the thermally annealed FETs is significantly improved from 9.66 to 0.562 V dec-1 through the energy of HCI generated by a strong horizontal electric field. In addition, the contact resistances (RSD), also called series resistances, extracted by a four-probe measurement and a Y-function method were also improved by decreasing to a 10th through the energy of HCI. To understand the asymmetrical characteristics of the channel after the stress, we performed electrical analysis, electrostatic force microscopy (EFM), and Raman spectroscopy.
ABSTRACT
Through time-dependent defect spectroscopy and low-frequency noise measurements, we investigate and characterize the differences of carrier trapping processes occurred by different interfaces (top/sidewall) of the gate-all-around silicon nanosheet field-effect transistor (GAA SiNS FET). In a GAA SiNS FET fabricated by the top-down process, the traps at the sidewall interface significantly affect the device performance as the width decreases. Compare to expectations, as the width of the device decreases, the subthreshold swing (SS) increases from 120 to 230 mV/dec, resulting in less gate controllability. In narrow-width devices, the effect of traps located at the sidewall interface is significantly dominant, and the 1/f 2 noise, also known as generation-recombination (G-R) noise, is clearly appeared with an increased time constant (τ i ). In addition, the probability density distributions for the normalized current fluctuations (ΔI D) show only one Gaussian in wide-width devices, whereas they are separated into four Gaussians with increased in narrow-width devices. Therefore, fitting is performed through the carrier number fluctuation-correlated with mobility fluctuations model that separately considered the effects of sidewall. In narrow-width GAA SiNS FETs, consequently, the extracted interface trap densities (N T ) distribution becomes more dominant, and the scattering parameter ([Formula: see text]) distribution increases by more than double.
ABSTRACT
The negative and positive aging effects of quantum dot (QD) light-emitting diodes (QLEDs) have received considerable attention in recent years and various analysis methods have been discussed. Here, we introduce a new approach to understand the aging effect of QLEDs, which is to diagnose the behavior of carriers and traps at interfaces between each layer of the QLEDs and inside the layers themselves. In particular, low-frequency noise (LFN) measurement and the analysis of current in the QLEDs were introduced to investigate the trapping/de-trapping behaviors of carriers in the defect states in the devices. A flicker noise was observed before the carriers are injected into the QD emitting layer, while the exciton generation-recombination (G-R) noise and shot noise were observed when the electrons were injected. A correlated noise, which is the correlated model of the trapping/de-trapping of the carriers near and/or inside the QDs and the exciton recombination, was also observed above the turn-on voltage. In addition, when the devices were aged with a constant current source, rapid increases in the luminance and external quantum efficiency (EQE) were observed for up to 50 h. After 100 h of the current aging, however, the devices were negatively aged with the reduced EQE. The LFN analysis results imply that the aging phenomena mainly depend on the trapping/de-trapping of carriers. In addition to the LFN analysis, we also investigated the current density-voltage-luminance and capacitance-voltage characteristics of the devices to clarify the aging behaviors in QLEDs.