Abstract
The mixing efficiency of stratified turbulence in geophysical fluids has been the subject of considerable controversy. A simple parameterization, devised decades ago when empirical knowledge ...was scarce, has held up remarkably well. The parameterization rests on the assumption that the flux coefficient Γ has the uniform value 0.2. This note provides a physical explanation for Γ = 0.2 in terms of the “marginal instability” property of forced stratified shear flows, and also sketches a path toward improving on that simple picture by examining cases where it fails.
Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the ...currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.
Turbulent mixing of heat and momentum in the stably-stratified ocean interior occurs in discrete events driven by vertical variations of the horizontal velocity. Typically, these events have been ...modelled assuming an initially laminar stratified shear flow which develops wavelike instabilities, becomes fully turbulent, and then relaminarizes into a stable state. However, in the real ocean there is always some level of turbulence left over from previous events. Using direct numerical simulations, we show that the evolution of a stably-stratified shear layer may be significantly modified by pre-existing turbulence. The classical billow structure associated with Kelvin–Helmholtz instability is suppressed and eventually eliminated as the strength of the initial turbulence is increased. A corresponding energetics analysis shows that potential energy changes and dissipation of kinetic energy depend non-monotonically on initial turbulence strength, with the largest effects when initial turbulence is present but insufficient to prevent billow formation. The mixing efficiency decreases with increasing initial turbulence amplitude as the development of the Kelvin–Helmholtz billow, with its large pre-turbulent mixing efficiency, is arrested.
Resting state functional connectivity is defined in terms of temporal correlations between physiologic signals, most commonly studied using functional magnetic resonance imaging. Major features of ...functional connectivity correspond to structural (axonal) connectivity. However, this relation is not one-to-one. Interhemispheric functional connectivity in relation to the corpus callosum presents a case in point. Specifically, several reports have documented nearly intact interhemispheric functional connectivity in individuals in whom the corpus callosum (the major commissure between the hemispheres) never develops. To investigate this question, we assessed functional connectivity before and after surgical section of the corpus callosum in 22 patients with medically refractory epilepsy. Section of the corpus callosum markedly reduced interhemispheric functional connectivity. This effect was more profound in multimodal associative areas in the frontal and parietal lobe than primary regions of sensorimotor and visual function. Moreover, no evidence of recovery was observed in a limited sample in which multiyear, longitudinal follow-up was obtained. Comparison of partial vs. complete callosotomy revealed several effects implying the existence of polysynaptic functional connectivity between remote brain regions. Thus, our results demonstrate that callosal as well as extracallosal anatomical connections play a role in the maintenance of interhemispheric functional connectivity.
Turbulence in geophysical flows tends to organize itself so that the mean flow remains close to a stability boundary in parameter space. That characteristic suggests self-organized criticality (SOC), ...a statistical property that has been identified in a range of complex phenomena including earthquakes, forest fires and solar flares. This note explores the relationship between the properties of forced, sheared, stratified turbulence (as found in oceans, atmospheres and other geophysical fluids) and those of SOC. Self-organization to the critical state is demonstrated in a wide range of cases drawn mostly (but not entirely) from in situ observations of ocean turbulence. Turbulent events in the ocean also exhibit a second characteristic associated with SOC: their sizes follow a power-law distribution indicating self-similarity. These results suggest SOC as a new conceptual foundation for the study of geophysical turbulence, an explanation for the mixing efficiency of ocean turbulence and a potential for cross-fertilization with other areas of geophysics.
Novel methods are necessary to reduce morbidity and mortality of patients suffering from infections with Pseudomonas aeruginosa. Being the most common infectious species of the Pseudomonas genus, P. ...aeruginosa is the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this species, an effective universal treatment method for P. aeruginosa infection still eludes investigators, despite the extensive research in this area.
We report bacterial inhibition by iron-oxide (nominally magnetite) nanoparticles (NPs) alone, having a mean hydrodynamic diameter of ~ 16 nm, as well as alginate-capped iron-oxide NPs. Alginate capping increased the average hydrodynamic diameter to ~ 230 nm. We also investigated alginate-capped iron-oxide NP-drug conjugates, with a practically unchanged hydrodynamic diameter of ~ 232 nm. Susceptibility and minimum inhibitory concentration (MIC) of the NPs, NP-tobramycin conjugates, and tobramycin alone were determined in the PAO1 bacterial colonies. Investigations into susceptibility using the disk diffusion method were done after 3 days of biofilm growth and after 60 days of growth. MIC of all compounds of interest was determined after 60-days of growth, to ensure thorough establishment of biofilm colonies.
Positive inhibition is reported for uncapped and alginate-capped iron-oxide NPs, and the corresponding MICs are presented. We report zero susceptibility to iron-oxide NPs capped with polyethylene glycol, suggesting that the capping agent plays a major role in enabling bactericidal ability in of the nanocomposite. Our findings suggest that the alginate-coated nanocomposites investigated in this study have the potential to overcome the bacterial biofilm barrier. Magnetic field application increases the action, likely via enhanced diffusion of the iron-oxide NPs and NP-drug conjugates through mucin and alginate barriers, which are characteristic of cystic-fibrosis respiratory infections. We demonstrate that iron-oxide NPs coated with alginate, as well as alginate-coated magnetite-tobramycin conjugates inhibit P. aeruginosa growth and biofilm formation in established colonies. We have also determined that susceptibility to tobramycin decreases for longer culture times. However, susceptibility to the iron-oxide NP compounds did not demonstrate any comparable decrease with increasing culture time. These findings imply that iron-oxide NPs are promising lower-cost alternatives to silver NPs in antibacterial coatings, solutions, and drugs, as well as other applications in which microbial abolition or infestation prevention is sought.
Abstract
Turbulent mixing produced by breaking of internal waves plays an important role in setting the patterns of downwelling and upwelling of deep dense waters and thereby helps sustain the global ...deep ocean overturning circulation. A key parameter used to characterize turbulent mixing is its efficiency, defined here as the fraction of the energy available to turbulence that is invested in mixing. Efficiency is conventionally approximated by a constant value near one sixth. Here we show that efficiency varies significantly in the abyssal ocean and can be as large as approximately one third in density stratified regions near topographic features. Our results indicate that variations in efficiency exert a first‐order control over the rate of overturning of the lower branch of the meridional overturning circulation.
Key Points
Efficiency of turbulent mixing in the abyssal ocean is highly variable, as opposed to being considered a constant traditionally
Variations in mixing efficiency has a leading order impact on the rate of overturning of the abyssal branch of circulation
Abyssal ocean turbulence plays a leading role in regulating the ocean's role in the carbon cycle and likely other tracer budgets
In this paper, the sandwich tubes, which consist of thin-walled circular tubes with aluminium foam core, were proposed as energy absorption devices. The sandwich tubes were laterally crushed under ...quasi-static loading conditions. Detailed finite element model, validated against existing experimental results, was developed using the explicit code (ANSYS-LSDYNA) to assess the energy absorption responses and deformation modes. Response surface methodology (RSM) was employed in parallel with the finite element models to perform both parametric studies and multi-objective optimization in order to establish the optimal configuration of the sandwich tube. Sampling designs of the sandwich tubes were constructed based on a D – optimal design of experiment (DOE) method. Factorial analysis was performed using the DOE results to investigate the influences of the geometric parameters on the responses of sandwich tubes. In addition, multi-objective optimization design (MOD) of the sandwich tubes is carried out by adopting a desirability approach. It was found that the tube with a minimum diameter of the inner layer and a maximum foam thickness are more suitable for use as energy absorbing components.
•The energy absorption characteristics of sandwich tubes are investigated under lateral loading.•The crush behaviour of sandwich tube is evaluated via 3D finite element modelling and response surface method.•The optimal design of the sandwich tubes was obtained via Desirability approach.•The optimal design was found to have a minimum diameter of the inner layer and a maximum foam thickness.
Pulmonary delivery of biopharmaceuticals may enable targeted local therapeutic effect and noninvasive systemic administration. Dry powder inhaler (DPI) delivery is an established patient-friendly ...approach for delivering large molecules to the lungs; however, the complexities of balancing protein stability with aerosol performance require that the design space of biopharmaceutical DPI formulations is rigorously explored. Utilizing four rationally selected formulations obtained using identical atomization conditions, an extensive study of the effect of the particle formation process (spray drying or spray freeze-drying) on powder properties, aerosol performance, and protein stability was performed. Multiple linear regression analysis was used to understand the relationship between powder properties, device dispersion mechanism, and aerosol performance. Spray drying and spray freeze-drying, despite the same spraying conditions, produced powders with vastly different physical characteristics, though similar aerosol performance. The resulting regression model points to the significance of particle size, density, and surface properties on the resulting aerosol performance, with these factors weighing differently according to the device dispersion mechanism utilized (shear-based or impaction-based). The physical properties of the produced spray dried and spray freeze-dried powders have differing implications for long-term stability, which will be explored extensively in a future study.
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