Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against CCR5 are being investigated. Here, we explored the role of CCR5 ...and its ligands across the immunologic spectrum of COVID-19. We used a bioinformatics approach to predict and model the immunologic phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 224 individuals including healthy controls and patients spanning the COVID-19 disease continuum. We assessed the plasma and isolated peripheral blood mononuclear cells (PBMCs) from 29 healthy controls, 26 Mild-Moderate COVID-19 individuals, 48 Severe COVID-19 individuals, and 121 individuals with post-acute sequelae of COVID-19 (PASC) symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients from each group. B-cells were significantly elevated compared to healthy control individuals (P<0.001) as was the CD14+, CD16+, CCR5+ monocytic subset (P<0.001). CD4 and CD8 positive T-cells expressing PD-1 as well as T-regulatory cells were significantly lower than healthy controls (P<0.001 and P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated compared to healthy controls (all P<0.001). Conversely GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were further analyzed and the classes were balanced using SMOTE. With a balanced working dataset, we constructed 3 random forest classifiers: a multi-class predictor, a Severe disease group binary classifier and a PASC binary classifier. Models were also analyzed for feature importance to identify relevant cytokines to generate a disease score. Multi-class models generated a score specific for the PASC patients and defined as S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, a score for the Severe COVID-19 patients was defined as S2 = (IL-6+sCD40L/1000 + VEGF/10 + 10*IL-10)/(IL-2 + IL-8). Severe COVID-19 patients are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While PASC patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.
The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect ...up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. That non-classical monocytes may be a source of inflammation in PASC warrants further study.
Increased use of pesticide is causing detrimental effects on non-target species worldwide. In this study, we examined the lethal and sub-lethal effects of fipronil and imidacloprid, two commonly used ...insecticides, on juvenile brown shrimp (Farfantepenaeus aztecus), one of the most commercially and ecologically important species in the United States. The effects of six concentrations of fipronil (0.0, 0.005, 0.01, 0.1, 1.0, and 3.0 μg/L) and six concentrations of imidacloprid (0.0, 0.5, 1.0, 15.0, 34.5, 320.0 μg/L) were tested in a laboratory. We examined five different endpoints: growth, moulting interval, survivorship, behavioral change, and body color change. Growth of shrimp was reduced significantly under higher concentrations of both insecticides. Under fipronil exposure, shrimp in control showed the shortest inter-moult interval (7.57 ± 2.17 day) compared with other treatments; similarly, in the imidacloprid experiment, moulting increased from 8.43 ± 2.52 day in control to 11.95 ± 4.9 day in 0.5 μg/L treatment. Higher concentrations of fipronil (1.0 and 3.0 μg/L) showed a 0.0% survival rate compared with 100% survival in the control and 0.005 μg/L treatment. Under imidacloprid, survivorship decreased from 100% in the control to 33.33% in the 320.0 μg/L treatment. The 96-h LC50 of fipronil was 0.12 μg/L, which makes brown shrimp one of the most sensitive invertebrates to the pesticide. Changes in behavior and body color were observed under both insecticides after different durations of exposures depending on concentrations. We conclude that, at the corresponding EPA benchmark concentrations, fipronil had more lethal effects than imidacloprid, and imidacloprid had more sub-lethal effects than fipronil. Both effects are of serious concern, and we suggest monitoring is necessary in estuaries.
Since 2012, the United States has seen a renewed focus on police killings of racial and ethnic minorities, as well as protest against such violence. Moreover, recent polling data show an ...intensification of long‐standing differences in Black and White Americans’ attitudes toward police violence and protest. Here, we review recent polling, as well as our own series of experiments, to elucidate racial divides in attention, attitudes, and reactions to police violence and protest against it (e.g., Black Lives Matter). In addition, we report linguistic analyses of descriptions (N = 195) of protest images, showing that Black participants better understand the causes of these protests (d = .30) and view them more positively (d = .38) than Whites. If we wish for consensus on how to address police violence and protest against it, we must understand how and why the sociopolitical reality of race leads to divergent views of these issues.
•A comprehensive model of the biomedical, psychological and neuroscientific models of biofeedback and neurofeedback learning.•Guidelines for the efficient design of biofeedback and neurofeedback ...protocols.•Research directions to investigate how biofeedback and neurofeedback works.
We believe that the missing keystone to design effective and efficient biofeedback and neurofeedback protocols is a comprehensive model of the mechanisms of feedback learning. In this manuscript we review the learning models in behavioral, developmental and cognitive psychology, and derive a synthetic model of the psychological perspective on biofeedback. We afterwards review the neural correlates of feedback learning mechanisms, and present a general neuroscience model of biofeedback. We subsequently show how biomedical engineering principles can be applied to design efficient feedback protocols. We finally present an integrative psychoengineering model of the feedback learning processes, and provide new guidelines for the efficient design of biofeedback and neurofeedback protocols. We identify five key properties, (1) perceptibility=can the subject perceive the biosignal?, (2) autonomy=can the subject regulate by himself?, (3) mastery=degree of control over the biosignal, (4) motivation=rewards system of the biofeedback, and (5) learnability=possibility of learning. We conclude with guidelines for the investigation and promotion of these properties in biofeedback protocols.
Low power dissipation and maximum battery runtime are crucial in portable electronics. With accurate and efficient circuit and battery models in hand, circuit designers can predict and optimize ...battery runtime and circuit performance. In this paper, an accurate, intuitive, and comprehensive electrical battery model is proposed and implemented in a Cadence environment. This model accounts for all dynamic characteristics of the battery, from nonlinear open-circuit voltage, current-, temperature-, cycle number-, and storage time-dependent capacity to transient response. A simplified model neglecting the effects of self-discharge, cycle number, and temperature, which are nonconsequential in low-power Li-ion-supplied applications, is validated with experimental data on NiMH and polymer Li-ion batteries. Less than 0.4% runtime error and 30-mV maximum error voltage show that the proposed model predicts both the battery runtime and I-V performance accurately. The model can also be easily extended to other battery and power sourcing technologies.
We present a novel process‐based morphodynamic model, which includes transport processes due to both velocity and acceleration skewness and a new formulation for intrawave motions, that successfully ...simulates observations of onshore sandbar migration. Results confirm findings of previous studies, in which each process was considered separately and in which sediment transport was computed from the observed water motion. However, our results indicate that accounting for the joint action of both velocity and acceleration skewnesses causes major improvement of the modeled onshore bar migration and is essential to accurately model the evolution of the entire cross‐shore bottom profile, when compared with observations. We also demonstrate that the morphodynamics in the shoaling zone are dominated by velocity skewness (bed shear stresses), while sediment transport induced by acceleration skewness (pressure gradients) controls the morphodynamics in the inner surf zone.
Key Points
A novel morphodynamic model describes field‐observed onshore sandbar migration
Both wave velocity and acceleration skewness are equally important
Accelerations control the inner surf zone; velocities dominate the shoaling zone
This paper presents a complete electromechanical (EM) model of piezoelectric transducers (PTs) independent of high or low coupling assumptions, vibration conditions, and geometry. The PT’s spring ...stiffness is modeled as part of the domain coupling transformer, and the piezoelectric EM coupling coefficient is modeled explicitly as a split inductor transformer. This separates the coupling coefficient from the coefficient used for conversion between mechanical and electrical domains, providing a more insightful understanding of the energy transfers occurring within a PT and allowing for analysis not previously possible. This also illustrates the role the PT’s spring plays in EM energy conversion. The model is analyzed and discussed from a circuits and energy harvesting perspective. Coupling between domains and how loading affects coupled energy are examined. Moreover, simple methods for experimentally extracting model parameters, including the coupling coefficient, are provided to empower engineers to quickly and easily integrate PTs in SPICE simulations for the rapid and improved development of PT interface circuits. The model and parameter extractions are validated by comparing them to the measured response of a physical cantilever-style PT excited by regular and irregular vibrations. In most cases, less than a 5–10% error between measured and simulated responses is observed.
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