Granular Brownian motion

We study the stochastic motion of an intruder in a dilute driven granular gas. All particles are coupled to a thermostat, representing the external energy source, which is the sum of random forces and a viscous drag. The dynamics of the intruder, in the large mass limit, is well described by a linear Langevin equation, combining the effects of the external bath and of the "granular bath". The drag and diffusion coefficients are calculated under few assumptions, whose validity is well verified in numerical simulations. We also discuss the non-equilibrium properties of the intruder dynamics, as well as the corrections due to finite packing fraction or finite intruder mass.Comment: 19 pages, 4 figures, in press on Journal of Statistical Mechanics: Theory and Experiment

EspA Acts as a Critical Mediator of ESX1-Dependent Virulence in Mycobacterium tuberculosis by Affecting Bacterial Cell Wall Integrity

Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1-mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall

Interferon-γ and Proliferation Responses to Salmonella enterica Serotype Typhi Proteins in Patients with S. Typhi Bacteremia in Dhaka, Bangladesh

Salmonella enterica serotype Typhi infection is a significant global public health problem and the cause of typhoid fever. Salmonella are intracellular pathogens, and cellular immune responses are required to control and clear Salmonella infections. Despite this, there are limited data on cellular immune responses during wild type S. Typhi infection in humans. Here we report the assessment of cellular immune responses in humans with S. Typhi bacteremia through a screening approach that permitted us to evaluate interferon-γ and proliferation responses to a number of S. Typhi antigens. We detected significant interferon-γ CD4 and CD8 responses, as well as proliferative responses, to a number of recombinantly purified S. Typhi proteins as well as membrane preparation in infected patients. Antigen-specific interferon-γ responses were present at the time of clinical presentation in patients and absent in healthy controls. These observations could assist in the development of interferon-γ-based diagnostic assays for typhoid fever

State legitimacy and famines in Sub-Saharan Africa

Political Economy of famines mainly focuses on political regimes to understand the role of institutions. In this paper, we investigate a broader concept, state legitimacy, and its role on one specific development outcome, famine management. State legitimacy refers to the political history of a country, meaning the embedding of state and society. Using a database of Sub-Saharan countries observed from 1980 to 2005, we use three empirical strategies: logit on famine occurrence, negative binomial regression and Arellano-Bond dynamic model on the number of years of famines. They all lead to the same results: there is room for a political economy of famine based on an analysis of state. State legitimacy prevents famines, controlling for shocks countries might go through, and controlling for the quality of government. The main contributions of this paper are first to consider the role of state legitimacy in the political economy of famines and second to apply the concept in an empirical analysis, using for the first time a state legitimacy variable

Fluctuation-Dissipation Relations in the imbalanced Wilson-Cowan model

The relation between spontaneous and stimulated brain activity is a fundamental question in neuroscience which has received wide attention in experimental studies. Recently, it has been suggested that the evoked response to external stimuli can be predicted from temporal correlations of spontaneous activity. Previous theoretical results, confirmed by the comparison with magnetoencephalography data for human brains, were obtained for the Wilson-Cowan model in the condition of balance of excitation and inhibition, a signature of a healthy brain. Here we extend previous studies to imbalanced conditions by examining a region of parameter space around the balanced fixed point. Analytical results are compared to numerical simulations of Wilson-Cowan networks. We evidence that in imbalanced conditions the functional form of the time correlation and response functions can show several behaviors, exhibiting also an oscillating regime caused by the emergence of complex eigenvalues. The analytical predictions are fully in agreement with numerical simulations, validating the role of cross-correlations in the response function. Furthermore, we identify the leading role of inhibitory neurons in controlling the overall activity of the system, tuning the level of excitability and imbalance