Perivascular macrophages create an intravascular niche for CD8 + T cell localisation prior to the onset of fatal experimental cerebral malaria

Objectives: The immunologic events that build up to the fatal neurological stage of experimental cerebral malaria (ECM) are incompletely understood. Here, we dissect immune cell behaviour occurring in the central nervous system (CNS) when Plasmodium berghei ANKA (PbA)-infected mice show only minor clinical signs. Methods: A 2-photon intravital microscopy (2P-IVM) brain imaging model was used to study the spatiotemporal context of early immunological events in situ during ECM. Results: Early in the disease course, antigen-specific CD8+ T cells came in contact and arrested on the endothelium of post-capillary venules. CD8+ T cells typically adhered adjacent to, or were in the near vicinity of, perivascular macrophages (PVMs) that line post-capillary venules. Closer examination revealed that CD8+ T cells crawled along the inner vessel wall towards PVMs that lay on the abluminal side of large post-capillary venules. 'Activity hotspots' in large post-capillary venules were characterised by T-cell localisation, activated morphology and clustering of PVM, increased abutting of post-capillary venules by PVM and augmented monocyte accumulation. In the later stages of infection, when mice exhibited neurological signs, intravascular CD8+ T cells increased in number and changed their behaviour, actively crawling along the endothelium and displaying frequent, short-term interactions with the inner vessel wall at hotspots. Conclusion: Our study suggests an active interaction between PVM and CD8+ T cells occurs across the blood-brain barrier (BBB) in early ECM, which may be the initiating event in the inflammatory cascade leading to BBB alteration and neuropathology

Localization dynamics in a binary two-dimensional cellular automaton: the Diffusion Rule

We study a two-dimensional cellular automaton (CA), called Diffusion Rule (DR), which exhibits diffusion-like dynamics of propagating patterns. In computational experiments we discover a wide range of mobile and stationary localizations (gliders, oscillators, glider guns, puffer trains, etc), analyze spatio-temporal dynamics of collisions between localizations, and discuss possible applications in unconventional computing.Comment: Accepted to Journal of Cellular Automat

Could thermal fluctuations seed cosmic structure?

We examine the possibility that thermal, rather than quantum, fluctuations are responsible for seeding the structure of our universe. We find that while the thermalization condition leads to nearly Gaussian statistics, a Harrisson-Zeldovich spectrum for the primordial fluctuations can only be achieved in very special circumstances. These depend on whether the universe gets hotter or colder in time, while the modes are leaving the horizon. In the latter case we find a no-go theorem which can only be avoided if the fundamental degrees of freedom are not particle-like, such as in string gases near the Hagedorn phase transition. The former case is less forbidding, and we suggest two potentially successful ``warming universe'' scenarios. One makes use of the Phoenix universe, the other of ``phantom'' matter.Comment: minor corrections made, references added, matches the version accepted to PR

Partisan Views of the Economy

In this paper it is argued that political parties may have incentives to adopt a partisan view on the working of the economic system. Our approach is based on a dynamical spatial voting model in which political parties are policy oriented. This model revolves around two interrelated issues x and y. The policy maker sets x directly. There exist two views on the relationship between x and y. Model uncertainty confronts policy makers with the problem of the selection of a model to base their actions on. We show that if voters have imperfect information about the working of the economic system that model selection contains a strategic element. Policy makers are inclined to adopt a view on the working of the economic system which fits in with their preferences. There is no inherent logic that places monetarists to the right of New Economists. They have different models of economic mechanism, but they need not have different political values. A conservative can be a Keynesian and a liberal a monetarist. These combinations are in fact surprisingly rare. James Tobin, 1974,The New Economics One Decade Older, p. 62. I am greatly indebted to Peter Broer, Ben Heydra, Jos Jansen and Wilko Letterie for many helpful suggestions. Furthermore, I would like to thank an anonymous referee for his comments

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Anthropogenic environmental drivers of antimicrobial resistance in wildlife

The isolation of antimicrobial resistant bacteria (ARB) from wildlife living adjacent to humans has led to the suggestion that such antimicrobial resistance (AMR) is anthropogenically driven by exposure to antimicrobials and ARB. However, ARB have also been detected in wildlife living in areas without interaction with humans. Here, we investigated patterns of resistance in Escherichia coli isolated from 408 wild bird and mammal faecal samples. AMR and multi-drug resistance (MDR) prevalence in wildlife samples differed significantly between a Sewage Treatment Plant (STP; wastes of antibiotic-treated humans) and a Farm site (antibiotic-treated livestock wastes) and Central site (no sources of wastes containing anthropogenic AMR or antimicrobials), but patterns of resistance also varied significantly over time and between mammals and birds. Over 30% of AMR isolates were resistant to colistin, a last-resort antibiotic, but resistance was not due to the mcr-1 gene. ESBL and AmpC activity were common in isolates from mammals. Wildlife were, therefore, harbouring resistance of clinical relevance. AMR E. coli, including MDR, were found in diverse wildlife species, and the patterns and prevalence of resistance were not consistently associated with site and therefore different exposure risks. We conclude that AMR in commensal bacteria of wildlife is not driven simply by anthropogenic factors, and, in practical terms, this may limit the utility of wildlife as sentinels of spatial variation in the transmission of environmental AMR

Majority Adder Implementation by Competing Patterns in Life-Like Rule B2/S2345

In this paper we present a two-dimensional chaotic cellular automaton, the Life rule B2/S2345, able to simulate the action of an adder with majority gates, stimulated by gliders collisions transformed as competing patterns. Values of Boolean variables are encoded into two types of patterns --- symmetric (FALSE) and asymmetric (TRUE) patterns -- which compete for the `empty' space when propagate in the channels. We construct basic logical gates and elementary arithmetical circuits by simulating logical signals with gliders reaction propagating geometrically restricted by stationary non-destructible still life. Therefore an implementation of universal logical gates and a majority binary adder is constructe

Error sources and data limitations for the prediction ofsurface gravity: a case study using benchmarks

Gravity-based heights require gravity values at levelled benchmarks (BMs), whichsometimes have to be predicted from surrounding observations. We use EGM2008 andthe Australian National Gravity Database (ANGD) as examples of model and terrestrialobserved data respectively to predict gravity at Australian national levelling network(ANLN) BMs. The aim is to quantify errors that may propagate into the predicted BMgravity values and then into gravimetric height corrections (HCs). Our results indicatethat an approximate ±1 arc-minute horizontal position error of the BMs causesmaximum errors in EGM2008 BM gravity of ~ 22 mGal (~55 mm in the HC at ~2200 melevation) and ~18 mGal for ANGD BM gravity because the values are not computed atthe true location of the BM. We use RTM (residual terrain modelling) techniques toshow that ~50% of EGM2008 BM gravity error in a moderately mountainous regioncan be accounted for by signal omission. Non-representative sampling of ANGDgravity in this region may cause errors of up to 50 mGals (~120 mm for the Helmertorthometric correction at ~2200 m elevation). For modelled gravity at BMs to beviable, levelling networks need horizontal BM positions accurate to a few metres, whileRTM techniques can be used to reduce signal omission error. Unrepresentative gravitysampling in mountains can be remedied by denser and more representative re-surveys,and/or gravity can be forward modelled into regions of sparser gravity