National interest may require distributing COVID-19 vaccines to other countries

As immunization campaigns are accelerating, understanding how to distribute the scarce doses of vaccines is of paramount importance and a quantitative analysis of the trade-offs involved in domestic-only versus cooperative distribution is still missing. In this study we use a network Susceptible-Infected-Removed (SIR) model to show circumstances under which it is in a country's self-interest to ensure other countries can obtain COVID-19 vaccines rather than focusing only on vaccination of their own residents. In particular, we focus our analysis on the United States and estimate the internal burden of COVID-19 disease under different scenarios about vaccine cooperation. We show that in scenarios in which the US has reached the threshold for domestic herd immunity, the US may find it optimal to donate doses to other countries with lower vaccination coverage, as this would allow for a sharp reduction in the inflow of infected individuals from abroad

Experimental evidence that changing beliefs about mask efficacy and social norms increase mask wearing for COVID-19 risk reduction:Results from the United States and Italy

In the absence of widespread vaccination for COVID-19, governments and public health officials have advocated for the public to wear masks during the pandemic. The decision to wear a mask in public is likely affected by both beliefs about its efficacy and the prevalence of the behavior. Greater mask use in the community may encourage others to follow this norm, but it also creates an incentive for individuals to free ride on the protection afforded to them by others. We report the results of two vignette-based experiments conducted in the United States (n = 3,100) and Italy (n = 2,659) to examine the causal relationship between beliefs, social norms, and reported intentions to engage in mask promoting behavior. In both countries, survey respondents were quota sampled to be representative of the country’s population on key demographics. We find that providing information about how masks protect others increases the likelihood that someone would wear a mask or encourage others to do so in the United States, but not in Italy. There is no effect of providing information about how masks protect the wearer in either country. Additionally, greater mask use increases intentions to wear a mask and encourage someone else to wear theirs properly in both the United States and Italy. Thus, community mask use may be self-reinforcing

General theory of instabilities for patterns with sharp interfaces in reaction-diffusion systems

An asymptotic method for finding instabilities of arbitrary $d$-dimensional large-amplitude patterns in a wide class of reaction-diffusion systems is presented. The complete stability analysis of 2- and 3-dimensional localized patterns is carried out. It is shown that in the considered class of systems the criteria for different types of instabilities are universal. The specific nonlinearities enter the criteria only via three numerical constants of order one. The performed analysis explains the self-organization scenarios observed in the recent experiments and numerical simulations of some concrete reaction-diffusion systems.Comment: 21 pages (RevTeX), 8 figures (Postscript). To appear in Phys. Rev. E (April 1st, 1996

An adjoint method for the assimilation of statistical characteristics into eddy-resolving ocean models

The study investigates perspectives of the parameter estimation problem with the adjoint method in eddy-resolving models. Sensitivity to initial conditions resulting from the chaotic nature of this type of model limits the direct application of the adjoint method by predictability. Prolonging the period of assimilation is accompanied by the appearance of an increasing number of secondary minima of the cost function that prevents the convergence of this method. In the framework of the Lorenz model it is shown that averaged quantities are suitable for describing invariant properties, and that secondary minima are for this type of data transformed into stochastic deviations. An adjoint method suitable for the assimilation of statistical characteristics of data and applicable on time scales beyond the predictability limit is presented. The approach assumes a greater predictability for averaged quantities. The adjoint to a prognostic model for statistical moments is employed for calculating cost function gradients that ignore the fine structure resulting from secondary minima. Coarse resolution versions of eddy-resolving models are used for this purpose. Identical twin experiments are performed with a quasigeostrophic model to evaluate the performance and limitations of this approach in improving models by estimating parameters. The wind stress curl is estimated from a simulated mean stream function. A very simple parameterization scheme for the assimilation of second-order moments is shown to permit the estimation of gradients that perform efficiently in minimizing cost functions

Breathing Current Domains in Globally Coupled Electrochemical Systems: A Comparison with a Semiconductor Model

Spatio-temporal bifurcations and complex dynamics in globally coupled intrinsically bistable electrochemical systems with an S-shaped current-voltage characteristic under galvanostatic control are studied theoretically on a one-dimensional domain. The results are compared with the dynamics and the bifurcation scenarios occurring in a closely related model which describes pattern formation in semiconductors. Under galvanostatic control both systems are unstable with respect to the formation of stationary large amplitude current domains. The current domains as well as the homogeneous steady state exhibit oscillatory instabilities for slow dynamics of the potential drop across the double layer, or across the semiconductor device, respectively. The interplay of the different instabilities leads to complex spatio-temporal behavior. We find breathing current domains and chaotic spatio-temporal dynamics in the electrochemical system. Comparing these findings with the results obtained earlier for the semiconductor system, we outline bifurcation scenarios leading to complex dynamics in globally coupled bistable systems with subcritical spatial bifurcations.Comment: 13 pages, 11 figures, 70 references, RevTex4 accepted by PRE http://pre.aps.or

Salt transiently inhibits mitochondrial energetics in mononuclear phagocytes

BACKGROUND: Dietary high salt (HS) is a leading risk factor for mortality and morbidity. Serum sodium transiently increases postprandially, but can also accumulate at sites of inflammation affecting differentiation and function of innate and adaptive immune cells. Here, we focus on how changes in extracellular sodium, mimicking alterations in the circulation and tissues, affect the early metabolic, transcriptional and functional adaption of human and murine mononuclear phagocytes (MNP). METHODS: Using Seahorse technology, pulsed stable isotope-resolved metabolomics and enzyme activity assays we characterize the central carbon metabolism and mitochondrial function of human and murine MNP under HS in vitro. HS as well as pharmacologic uncoupling of the electron transport chain (ETC) under normal salt (NS) is used to analyze mitochondrial function on immune cell activation and function (as determined by E.coli killing and CD4(+) T cell migration capacity). In two independent clinical studies we analyze the impact of a HS diet over two weeks (NCT02509962) and short-term salt challenge by a single meal (NCT04175249) on mitochondrial function of human monocytes in vivo. RESULTS: Extracellular sodium was taken up into the intracellular compartment followed by the inhibition of mitochondrial respiration in murine and human macrophages (MΦ). Mechanistically, HS reduces mitochondrial membrane potential, ETC complex II activity, oxygen consumption, and ATP production independently of the polarization status of MΦ. Subsequently, cell activation is altered with improved bactericidal function in HS-treated M1-like MΦ and diminished CD4(+) T cell migration in HS-treated M2-like MΦ. Pharmacologic uncoupling of the ETC under NS phenocopies HS-induced transcriptional changes and bactericidal function of human and murine MNP. Clinically, also in vivo rise in plasma sodium concentration within the physiological range reversibly reduces mitochondrial function in human monocytes. In both, a 14-day and single meal HS challenge, healthy volunteers displayed a plasma sodium increase of ̃x = 2mM and ̃x = 2.3mM, respectively, that correlated with decreased monocytic mitochondrial oxygen consumption. CONCLUSIONS: Our data identify the disturbance of mitochondrial respiration as the initial step by which HS mechanistically influences immune cell function. While these functional changes might help to resolve bacterial infections, a shift towards pro-inflammation could accelerate inflammatory CVD

Syk-Mediated Translocation of PI3Kδ to the Leading Edge Controls Lamellipodium Formation and Migration of Leukocytes

The non-receptor tyrosine kinase Syk is mainly expressed in the hematopoietic system and plays an essential role in β2 integrin-mediated leukocyte activation. To elucidate the signaling pathway downstream of Syk during β2 integrin (CD11/CD18)-mediated migration and extravasation of polymorphonuclear neutrophils (PMN), we generated neutrophil-like differentiated HL-60 (dHL-60) cells expressing a fluorescently tagged Syk mutant lacking the tyrosine residue at the position 323 (Syk-Tyr323) that is known to be required for the binding of the regulatory subunit p85 of the phosphatidylinositol 3-kinase (PI3K) class IA. Syk-Tyr323 was found to be critical for the enrichment of the catalytic subunit p110δ of PI3K class IA as well as for the generation of PI3K products at the leading edge of the majority of polarized cells. In accordance, the translocation of PI3K p110δ to the leading edge was diminished in Syk deficient murine PMN. Moreover, the expression of EGFP-Syk Y323F interfered with proper cell polarization and it impaired efficient migration of dHL-60 cells. In agreement with a major role of β2 integrins in the recruitment of phagocytic cells to sites of lesion, mice with a Syk-deficient hematopoietic system demonstrated impaired PMN infiltration into the wounded tissue that was associated with prolonged cutaneous wound healing. These data imply a novel role of Syk via PI3K p110δ signaling for β2 integrin-mediated migration which is a prerequisite for efficient PMN recruitment in vivo