Repeated cross-sectional sero-monitoring of SARS-CoV-2 in New York City.

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in China and has since caused a pandemic of coronavirus disease 2019 (COVID-19). The first case of COVID-19 in New York City was officially confirmed on 1 March 2020 followed by a severe local epidemic1. Here, to understand seroprevalence dynamics, we conduct a retrospective, repeated cross-sectional analysis of anti-SARS-CoV-2 spike antibodies in weekly intervals from the beginning of February to July 2020 using more than 10,000 plasma samples from patients at Mount Sinai Hospital in New York City. We describe the dynamics of seroprevalence in an 'urgent care' group, which is enriched in cases of COVID-19 during the epidemic, and a 'routine care' group, which more closely represents the general population. Seroprevalence increased at different rates in both groups; seropositive samples were found as early as mid-February, and levelled out at slightly above 20% in both groups after the epidemic wave subsided by the end of May. From May to July, seroprevalence remained stable, suggesting lasting antibody levels in the population. Our data suggest that SARS-CoV-2 was introduced in New York City earlier than previously documented and describe the dynamics of seroconversion over the full course of the first wave of the pandemic in a major metropolitan area.

Scale Invariance of a Spherical Unitary Fermi Gas.

A unitary Fermi gas in an isotropic harmonic trap is predicted to show scale and conformal symmetry that have important consequences in its thermodynamic and dynamical properties. By experimentally realizing a unitary Fermi gas in an isotropic harmonic trap, we demonstrate its universal expansion dynamics along each direction and at different temperatures. We show that as a consequence of SO(2,1) symmetry, the measured release energy is equal to that of the trapping energy. We further observe the breathing mode with an oscillation frequency twice the trapping frequency and a small damping rate, providing the evidence of SO(2,1) symmetry. In addition, away from resonance when scale invariance is broken, we determine the effective exponent γ that relates the chemical potential and average density along the BEC-BCS crossover, which qualitatively agrees with the mean field predictions. This Letter opens the possibility of studying nonequilibrium dynamics in a conformal invariant system in the future.

Novel Epitopes of the Influenza Virus N1 Neuraminidase Targeted by Human Monoclonal Antibodies.

Influenza virus neuraminidase (NA)-targeting antibodies are an independent correlate of protection against influenza. Antibodies against the NA act by blocking enzymatic activity, preventing virus release and transmission. As we advance the development of improved influenza virus vaccines that incorporate standard amounts of NA antigen, it is important to identify the antigenic targets of human monoclonal antibodies (mAbs). Here, we describe escape mutants generated by serial passage of A/Netherlands/602/2009 (H1N1)pdm09 in the presence of human anti-N1 mAbs. We observed escape mutations on the head domain of the N1 protein around the enzymatic site (S364N, N369T, and R430Q) and also detected escape mutations located on the sides and bottom of the NA (N88D, N270D, and Q313K/R). This work increases our understanding of how human antibody responses target the N1 protein. IMPORTANCE As improved influenza virus vaccines are being developed, the influenza virus neuraminidase (NA) is becoming an important new target for immune responses. By identifying novel epitopes of anti-NA antibodies, we can improve vaccine design. Additionally, characterizing escape mutations in these epitopes aids in identifying NA antigenic drift in circulating viruses.

What do you have in mind? ERP markers of visual and auditory imagery.

This study aimed to investigate the psychophysiological markers of imagery processes through EEG/ERP recordings. Visual and auditory stimuli representing 10 different semantic categories were shown to 30 healthy participants. After a given interval and prompted by a light signal, participants were asked to activate a mental image corresponding to the semantic category for recording synchronized electrical potentials. Unprecedented electrophysiological markers of imagination were recorded in the absence of sensory stimulation. The following peaks were identified at specific scalp sites and latencies, during imagination of infants (centroparietal positivity, CPP, and late CPP), human faces (anterior negativity, AN), animals (anterior positivity, AP), music (P300-like), speech (N400-like), affective vocalizations (P2-like) and sensory (visual vs auditory) modality (PN300). Overall, perception and imagery conditions shared some common electro/cortical markers, but during imagery the category-dependent modulation of ERPs was long latency and more anterior, with respect to the perceptual condition. These ERP markers might be precious tools for BCI systems (pattern recognition, classification, or A.I. algorithms) applied to patients affected by consciousness disorders (e.g., in a vegetative or comatose state) or locked-in-patients (e.g., spinal or SLA patients).

Critic Learning-Based Safe Optimal Control for Nonlinear Systems with Asymmetric Input Constraints and Unmatched Disturbances.

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.

Synthesis of gallic acid amide derivatives containing 1,3,4-thiadiazole and their inhibitory activity on Vibrio harveyi.

Using Gallic acid as raw material, 1-(substituted aromatic acyl)-4-(3,4,5-trihydroxybenzoyl) thiosemicarbazone was prepared by a two-step reaction and a series of brand-new gallic acid amide derivatives that contained 1,3,4-thiadiazole were synthesized by cyclic reaction. The newly prepared compounds' Vibrio harveyi inhibition activities were evaluated. The results indicated that all compounds showed different degree of inhibitory activity on Vibrio harveyi. Among them, the best inhibition effect was shown by compound 5b and its minimum inhibitory concentration (MIC) was 0.0313mg/mL.

Differential T-Cell Reactivity to Endemic Coronaviruses and SARS-CoV-2 in Community and Health Care Workers.

Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2-seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2-infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego. CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.

Characterization of Novel Cross-Reactive Influenza B Virus Hemagglutinin Head Specific Antibodies That Lack Hemagglutination Inhibition Activity.

Humoral immune responses to influenza virus vaccines in elderly individuals are poorly adapted toward new antigenically drifted influenza virus strains. Instead, older individuals respond in an original antigenic sin fashion and produce much more cross-reactive but less potent antibodies. Here, we investigated four influenza B virus hemagglutinin (HA) head specific, hemagglutination inhibition-inactive monoclonal antibodies (MAbs) from elderly individuals. We found that they were broadly reactive within the B/Victoria/2/1987-like lineage, and two were highly cross-reactive with B/Yamagata/16/1988-like lineage viruses. The MAbs were found to be neutralizing, to utilize Fc effector functions, and to be protective against lethal viral challenge in a mouse model. In order to identify residues on the influenza B virus hemagglutinin interacting with the MAbs, we generated escape mutant viruses. Interestingly, escape from these MAbs led to numerous HA mutations within the head domain, including in the defined antigenic sites. We observed that each individual escape mutant virus was able to avoid neutralization by its respective MAb along with other MAbs in the panel, although in many cases binding activity was maintained. Point mutant viruses indicated that K90 is critical for the neutralization of two MAbs, while escape from the other two MAbs required a combination of mutations in the hemagglutinin. Three of four escape mutant viruses had increased lethality in the DBA2/J mouse model. Our work indicates that these cross-reactive antibodies have the potential to cause antigenic drift in the viral population by driving mutations that increase virus fitness. However, binding activity and cross-neutralization were maintained by a majority of antibodies in the panel, suggesting that this drift may not lead to escape from antibody-mediated protection.IMPORTANCE Understanding the immune response that older individuals mount to influenza virus vaccination and infection is critical in order to design better vaccines for this age group. Here, we show that older individuals make broadly neutralizing antibodies that have no hemagglutination-inhibiting activity and are less potent than strain-specific antibodies. These antibodies could drive viral escape from neutralization but did not result in escape from binding. Given their different mechanisms of action, they might retain protective activity even against escape variants.

Ground-State Phase Diagram of a Spin-Orbital-Angular-Momentum Coupled Bose-Einstein Condensate.

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.

Contact Theory for Spin-Orbit-Coupled Fermi Gases.

We develop the contact theory for spin-orbit-coupled Fermi gases. By using a perturbation method, we derive analytically the universal two-body behavior at short distance, which does not depend on the short-range details of interatomic potentials. We find that two new scattering parameters need to be introduced because of spin-orbit coupling, besides the traditional s- and p-wave scattering length (volume) and effective ranges. This is a general and unique feature for spin-orbit-coupled systems. Consequently, two new adiabatic energy relations with respect to the new scattering parameters are obtained, in which a new contact is involved because of spin-orbit coupling. In addition, we derive the asymptotic behavior of the large-momentum distribution, and find that the subleading tail is corrected by the new contact. This work paves the way for exploring the profound properties of spin-orbit-coupled many-body systems, according to two-body solutions.

Phylogenetic and biological characterization of three K1203 (H5N8)-like avian influenza A virus reassortants in China in 2014.

Three H5N8 avian influenza viruses isolated from domestic geese in China in 2014 were characterized phylogenetically and biologically. Phylogenetic analysis of the complete genomic sequences of the three isolates from this study and those of 61 other H5N8 viruses retrieved from the GISAID platform indicated that, chronologically and geographically, all H5N8 viruses of the Asian H5N1 HA lineage of clade 2.3.4.4 are the direct descendents of the K1203 (H5N8)-like viruses first isolated in China in 2010. The three viruses from this study shared high sequence similarity in all eight gene segments with three other isolates from China in 2013, and two Korean isolates were distinct from the recently circulating reassortants causing outbreaks in Asia, Europe and the United States in 2014 and 2015. In vitro viral growth curves indicated that these H5N8 viruses replicated to high titers in CEF, DEF, MDCK and A549 cells but to significantly lower titers in Vero cells. Pathogenicity studies in vivo indicated that these viruses were all highly virulent to chickens and mallard ducks, while they varied from moderate to high virulence in mice. Additionally, hemagglutination assays using α-2,3-sialidase-treated goose red blood cells and solid-phase direct binding assays with different glycans demonstrated that the three viruses could bind to both avian-type SAα-2,3Gal and human-type SAα-2,6Gal receptors. Our findings confirmed the progenitor nature of the K1203-like viruses in generating recent prevalent clade 2.3.4.4 H5N8 reassortants, which have caused tremendous damage to the poultry industry and are a potential threat to public health.

Two amino acid substitutions in the haemagglutinin of the 2009 pandemic H1N1 virus decrease direct-contact transmission in guinea pigs.

The 2009 pandemic H1N1 influenza A virus spread across the globe and caused the first influenza pandemic of the 21st century. Many of the molecular factors that contributed to the airborne transmission of this pandemic virus have been determined; however, the direct-contact transmission of this virus remains poorly understood. In this study, we report that a combination of two mutations (N159D and Q226R) in the haemagglutinin (HA) protein of the representative 2009 H1N1 influenza virus A/California/04/2009 (CA04) caused a switch in receptor binding preference from the α2,6-sialoglycan to the α2,3-sialoglycan receptor, and decreased the binding intensities for both glycans. In conjunction with a significantly decreased replication efficiency in the nasal epithelium, this limited human receptor binding affinity resulted in inefficient direct-contact transmission of CA04 between guinea pigs. Our findings highlight the role of the HA gene in the transmission of the influenza virus.

Manipulation of p-wave scattering of cold atoms in low dimensions using the magnetic field vector.

It is well known that the magnetic Feshbach resonances of cold atoms are sensitive to the magnitude of the external magnetic field. Much less attention has been paid to the direction of such a field. In this work we calculate the scattering properties of spin polarized fermionic atoms in reduced dimensions, near a p-wave Feshbach resonance. Because of the spatial anisotropy of the p-wave interaction, the scattering has a nontrivial dependence on both the magnitude and the direction of the magnetic field. In addition, we identify an inelastic scattering process which is impossible in the isotropic-interaction model; the rate of this process depends considerably on the direction of the magnetic field. Significantly, an Einstein-Podolsky-Rosen entangled pair of identical fermions may be produced during this inelastic collision. This work opens a new method to manipulate resonant cold atomic interactions.

Differences in transmissibility and pathogenicity of reassortants between H9N2 and 2009 pandemic H1N1 influenza A viruses from humans and swine.

Both H9N2 subtype avian influenza and 2009 pandemic H1N1 viruses (pH1N1) can infect humans and pigs, which provides the opportunity for virus reassortment, leading to the genesis of new strains with potential pandemic risk. In this study, we generated six reassortant H9 viruses in the background of three pH1N1 strains from different hosts (A/California/04/2009 [CA04], A/Swine/Jiangsu/48/2010 [JS48] and A/Swine/Jiangsu/285/2010 [JS285]) by replacing either the HA (H9N1-pH1N1) or both the HA and NA genes (H9N2-pH1N1) from an h9.4.2.5-lineage H9N2 subtype influenza virus, A/Swine/Taizhou/5/08 (TZ5). The reassortant H9 viruses replicated to higher titers in vitro and in vivo and gained both efficient transmissibility in guinea pigs and increased pathogenicity in mice compared with the parental H9N2 virus. In addition, differences in transmissibility and pathogenicity were observed among these reassortant H9 viruses. The H9N2-pH1N1viruses were transmitted more efficiently than the corresponding H9N1-pH1N1 viruses but showed significantly decreased pathogenicity. One of the reassortant H9 viruses that were generated, H9N-JS48, showed the highest virulence in mice and acquired respiratory droplet transmissibility between guinea pigs. These results indicate that coinfection of swine with H9N2 and pH1N1viruses may pose a threat for humans if reassortment occurs, emphasizing the importance of surveillance of these viruses in their natural hosts.

Multiple side-band generation for two-frequency components injected into a tapered amplifier.

We have experimentally studied multiple side-band generation for two-frequency components injected into a tapered amplifier (TA) and demonstrated its effects on atomic laser cooling. A heterodyne frequency-beat measurement and a Fabry-Perot interferometer have been applied to analyze the side-band generation with different experimental parameters, such as frequency difference, injection laser power, and TA current. In laser-cooling potassium40 and potassium41 with hyperfine splitting of 1.3 GHz and 254 MHz, respectively, the side-band generation with a small frequency difference has a significant effect on the number of trapped atoms.

Event-related brain potential markers of visual and auditory perception: A useful tool for brain computer interface systems.

Objective: 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. Methods: 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. Results: 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. Conclusion: The data showed a high level of accuracy (p ≤ 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.

Nomogram models for the prognosis of cervical cancer: A SEER-based study.

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.

Mutations in the Hemagglutinin Stalk Domain Do Not Permit Escape from a Protective, Stalk-Based Vaccine-Induced Immune Response in the Mouse Model.

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 in vitro but showed attenuation in an in vivo 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.IMPORTANCE 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.