Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious ...virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.
In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and ...divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
Some persons who have recovered from Covid-19 have antibodies to the spike protein of SARS-CoV-2. In 43 such persons who had received a first mRNA vaccine dose, high levels of neutralizing antispike ...antibodies were produced — in many cases even higher than after a second dose in 67 persons without baseline antibodies to the virus. Systemic reactions were more common in those seropositive before vaccination.
By inducing a Raman transition using a pair of Gaussian and Laguerre-Gaussian laser beams, we realize a ^{87}Rb condensate whose orbital angular momentum (OAM) and its internal spin states are ...coupled. By varying the detuning and the coupling strength of the Raman transition, we experimentally map out the ground-state phase diagram of the system for the first time. The transitions between different phases feature a discontinuous jump of the OAM and the spin polarization, and hence are of first order. We demonstrate the hysteresis loop associated with such first-order phase transitions. The role of interatomic interaction is also elucidated. Our work paves the way to explore exotic quantum phases in the spin-orbital-angular-momentum coupled quantum gases.
A majority of BCI systems, enabling communication with patients with locked-in syndrome, are based on electroencephalogram (EEG) frequency analysis (e.g., linked to motor imagery) or P300 detection. ...Only recently, the use of event-related brain potentials (ERPs) has received much attention, especially for face or music recognition, but neuro-engineering research into this new approach has not been carried out yet. The aim of this study was to provide a variety of reliable ERP markers of visual and auditory perception for the development of new and more complex mind-reading systems for reconstructing the mental content from brain activity.
A total of 30 participants were shown 280 color pictures (adult, infant, and animal faces; human bodies; written words; checkerboards; and objects) and 120 auditory files (speech, music, and affective vocalizations). This paradigm did not involve target selection to avoid artifactual waves linked to decision-making and response preparation (e.g., P300 and motor potentials), masking the neural signature of semantic representation. Overall, 12,000 ERP waveforms × 126 electrode channels (1 million 512,000 ERP waveforms) were processed and artifact-rejected.
Clear and distinct category-dependent markers of perceptual and cognitive processing were identified through statistical analyses, some of which were novel to the literature. Results are discussed from the view of current knowledge of ERP functional properties and with respect to machine learning classification methods previously applied to similar data.
The data showed a high level of accuracy (
≤ 0.01) in the discriminating the perceptual categories eliciting the various electrical potentials by statistical analyses. Therefore, the ERP markers identified in this study could be significant tools for optimizing BCI systems pattern recognition or artificial intelligence (AI) algorithms applied to EEG/ERP signals.
Background
Cervical cancer (CC) is one of the most common cancers in women. This study aimed to investigate the clinical and non-clinical features that may affect the prognosis of patients with CC ...and to develop accurate prognostic models with respect to overall survival (OS) and cancer-specific survival (CSS).
Methods
We identified 11,148 patients with CC from the SEER (Surveillance, Epidemiology, and End Results) database from 2010 to 2016. Univariate and multivariate Cox regression models were used to identify potential predictors of patients’ survival outcomes (OS and CSS). We selected meaningful independent parameters and developed nomogram models for 1-, 3-, and 5-year OS and CSS
via
R tools. Model performance was evaluated by C-index and receiver operating characteristic curve. Furthermore, calibration curves were plotted to compare the predictions of nomograms with observed outcomes, and decision curve analysis (DCA) and clinical impact curves (CICs) were used to evaluate the clinical effectiveness of the nomograms.
Results
All eligible patients (n=11148) were randomized at a 7:3 ratio into training (n=7803) and validation (n=3345) groups. Ten variables were identified as common independent predictors of OS and CSS: insurance status, grade, histology, chemotherapy, metastasis number, tumor size, regional nodes examined, International Federation of Obstetrics and Gynecology stage, lymph vascular space invasion (LVSI), and radiation. The C-index values for OS (0.831 and 0.824) and CSS (0.844 and 0.841) in the training cohorts and validation cohorts, respectively, indicated excellent discrimination performance of the nomograms. The internal and external calibration plots indicated excellent agreement between nomogram prediction and actual survival, and the DCA and CICs reflected favorable potential clinical effects.
Conclusions
We constructed nomograms that could predict 1-, 3-, and 5-year OS and CSS in patients with CC. These tools showed near-perfect accuracy and clinical utility; thus, they could lead to better patient counseling and personalized and tailored treatment to improve clinical prognosis.
In this paper, the safe optimal control method for continuous-time (CT) nonlinear safety-critical systems with asymmetric input constraints and unmatched disturbances based on the adaptive dynamic ...programming (ADP) is investigated. Initially, a new non-quadratic form function is implemented to effectively handle the asymmetric input constraints. Subsequently, the safe optimal control problem is transformed into a two-player zero-sum game (ZSG) problem to suppress the influence of unmatched disturbances, and a new Hamilton-Jacobi-Isaacs (HJI) equation is introduced by integrating the control barrier function (CBF) with the cost function to penalize unsafe behavior. Moreover, a damping factor is embedded in the CBF to balance safety and optimality. To obtain a safe optimal controller, only one critic neural network (CNN) is utilized to tackle the complex HJI equation, leading to a decreased computational load in contrast to the utilization of the conventional actor-critic network. Then, the system state and the parameters of the CNN are uniformly ultimately bounded (UUB) through the application of the Lyapunov stability method. Lastly, two examples are presented to confirm the efficacy of the presented approach.
Current seasonal influenza virus vaccines target regions of the hemagglutinin (HA) head domain that undergo constant antigenic change, forcing the painstaking annual reformulation of vaccines. The ...development of broadly protective or universal influenza virus vaccines that induce cross-reactive, protective immune responses could circumvent the need to reformulate current seasonal vaccines. Many of these vaccine candidates target the HA stalk domain, which displays epitopes conserved within and across influenza virus subtypes, including those with pandemic potential. While HA head-mediated antigenic drift is well understood, the potential for antigenic drift in the stalk domain is understudied. Using a panel of HA stalk-specific monoclonal antibodies (MAbs), we applied selection pressure to the stalk domain of A/Netherlands/602/2009 (pdmH1N1) to determine fitness and phenotypes of escape mutant viruses (EMVs). We found that HA stalk MAbs with lower cross-reactivity caused single HA stalk escape mutations, whereas MAbs with broader cross-reactivity forced multiple mutations in the HA. Each escape mutant virus greatly decreased mAb neutralizing activity, but escape mutations did not always ablate MAb binding or Fc-Fc receptor-based effector functions. Escape mutant viruses were not attenuated
but showed attenuation in an
mouse model. Importantly, mice vaccinated with a chimeric HA universal vaccine candidate were protected from lethal challenge with EMVs despite these challenge viruses containing escape mutations in the stalk domain. Our study indicates that while the HA stalk domain can mutate under strong MAb selection pressure, mutant viruses may have attenuated phenotypes and do not evade a polyclonal, stalk-based vaccine-induced response.
Broadly protective or universal influenza virus vaccines target viral epitopes that appear to be conserved. However, it is unclear whether the virus will be able to escape once immunological pressure is applied to these epitopes through vaccination of large proportions of the population. Studies that investigate the fitness and antigenic characteristics of viruses that escape immunological pressure on these conserved epitopes are therefore urgently needed.
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