Inverse Compton Scattering as the Source of Diffuse EUV Emission in the Coma Cluster of Galaxies

We have examined the hypothesis that the majority of the diffuse EUV flux in the Coma cluster is due to inverse Compton scattering of low energy cosmic ray electrons (0.16 < epsilon < 0.31 GeV) against the 3K black-body background. We present data on the two-dimensional spatial distribution of the EUV flux and show that these data provide strong support for a non-thermal origin for the EUV flux. However, we show that this emission cannot be produced by an extrapolation to lower energies of the observed synchrotron radio emitting electrons and an additional component of low energy cosmic ray electrons is required.Comment: 11 pages, 5 figure

The Physics of Cluster Mergers

Clusters of galaxies generally form by the gravitational merger of smaller clusters and groups. Major cluster mergers are the most energetic events in the Universe since the Big Bang. Some of the basic physical properties of mergers will be discussed, with an emphasis on simple analytic arguments rather than numerical simulations. Semi-analytic estimates of merger rates are reviewed, and a simple treatment of the kinematics of binary mergers is given. Mergers drive shocks into the intracluster medium, and these shocks heat the gas and should also accelerate nonthermal relativistic particles. X-ray observations of shocks can be used to determine the geometry and kinematics of the merger. Many clusters contain cooling flow cores; the hydrodynamical interactions of these cores with the hotter, less dense gas during mergers are discussed. As a result of particle acceleration in shocks, clusters of galaxies should contain very large populations of relativistic electrons and ions. Electrons with Lorentz factors gamma~300 (energies E = gamma m_e c^2 ~ 150 MeV) are expected to be particularly common. Observations and models for the radio, extreme ultraviolet, hard X-ray, and gamma-ray emission from nonthermal particles accelerated in these mergers are described.Comment: 38 pages with 9 embedded Postscript figures. To appear in Merging Processes in Clusters of Galaxies, edited by L. Feretti, I. M. Gioia, and G. Giovannini (Dordrecht: Kluwer), in press (2001

An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health

The preservation of cognitive abilities with aging is a priority both for individuals and nations given the aging populations of many countries. Recently the gut microbiome has been identified as a new territory to explore in relation to cognition. Experiments using rodents have identified a link between the gut microbiome and cognitive function, particularly that low microbial diversity leads to poor cognition function. Similar studies in humans could identify novel targets to encourage healthy cognition in an aging population. Here, we investigate the association of gut microbiota and cognitive function in a human cohort considering the influence of physical frailty. We analyzed 16S rRNA gene sequence data, derived from fecal samples obtained from 1,551 individuals over the age of 40. Cognitive data was collected using four cognitive tests: verbal fluency (n = 1,368), Deary-Liewald Reaction Time Test (DLRT; n = 873), Mini Mental State Examination (recall; n = 1,374) and Paired Associates Learning from the Cambridge Neuropsychological Test Automated Battery (CANTAB-PAL; n = 405). We use mixed effects models to identify associations with alpha diversity, operational taxonomic units (OTUs) and taxa and performed further analyses adjusting for physical frailty. We then repeated the analyses in a subset of individuals with dietary data, also excluding those using medications shown to influence gut microbiome composition. DLRT and verbal fluency were negatively associated with alpha diversity of the gut microbiota (False-Discovery Rate, FDR, p &lt; 0.05). However, when considering frailty as a covariate, only associations between the DLRT and diversity measures remained. Repeating analyses excluding Proton pump inhibitor (PPI) and antibiotic users and accounting for diet, we similarly observe significant negative associations between the DLRT and alpha diversity measures and a further negative association between DLRT and the abundance of the order Burkholderiales that remains significant after adjusting for host frailty. This highlights the importance of considering concurrent differences in physical health in studies of cognitive performance and suggests that physical health has a relatively larger association with the gut microbiome. However, the frailty independent cognitive-gut microbiota associations that were observed might represent important targets for further research, with potential for use in diagnostic surveillance in cognitive aging and interventions to improve vitality

Drones y el orden legal internacional. Tecnología, estrategia y largas cadenas de acción

The main thesis of this article is that the increasing recourse to the use of unmanned aerial systems in asymmetric warfare and the beginning routinization of U.S. drone operations represent part of an evolutionary change in the spatial ordering of global politics -- Using a heuristic framework based on actor-network theory, it is argued that practices of panoptic observation and selective airstrikes, being in need of legal justification, contribute to a reterritorialization of asymmetric conflicts -- Under a new normative spatial regime, a legal condition of state immaturity is constructed, which establishes a zone of conditional sovereignty subject to transnational aerial policing -- At the same time, this process is neither a deterministic result of the new technology nor a deliberate effect of policies to which drones are merely neutral instruments -- Rather, military technology and political decisions both form part of a long chain of action which has evolved under the specific circumstances of recent military interventionsEste artículo propone que la creciente utilización de sistemas aéreos no tripulados y la rutinización de sus operaciones en guerras asimétricas representan parte de un cambio evolutivo en el ordenamiento espacial de la política global -- Utilizando un marco heurístico basado en la teoría del actor-red, se argumenta que las prácticas de observación panóptica y ataques aéreos selectivos, carentes aún de justificación legal, contribuyen a una reterritorialización de los conflictos asimétricos -- En virtud de un nuevo régimen normativo espacial, se construye una condición legal de inmadurez estatal que facilita el establecimiento de una zona de soberanía condicionada, sometida a la vigilancia aérea transnacional -- Al mismo tiempo, esté proceso no es resultado predeterminado de la nueva tecnología, ni efecto deliberado de decisiones políticas para las que los drones son solo instrumentos neutros -- Antes que ello, la tecnología militar y las decisiones políticas forman parte importante de una larga cadena de acción que se ha desarrollado en las circunstancias específicas de intervenciones militares más reciente

Selective Inhibitors of Protozoan Protein N-myristoyltransferases as Starting Points for Tropical Disease Medicinal Chemistry Programs

Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections, using species-specific inhibitors. In order to identify inhibitors of protozoan NMTs, we chose to screen a diverse subset of the Pfizer corporate collection against Plasmodium falciparum and Leishmania donovani NMTs. Primary screening hits against either enzyme were tested for selectivity over both human NMT isoforms (Hs1 and Hs2) and for broad-spectrum anti-protozoan activity against the NMT from Trypanosoma brucei. Analysis of the screening results has shown that structure-activity relationships (SAR) for Leishmania NMT are divergent from all other NMTs tested, a finding not predicted by sequence similarity calculations, resulting in the identification of four novel series of Leishmania-selective NMT inhibitors. We found a strong overlap between the SARs for Plasmodium NMT and both human NMTs, suggesting that achieving an appropriate selectivity profile will be more challenging. However, we did discover two novel series with selectivity for Plasmodium NMT over the other NMT orthologues in this study, and an additional two structurally distinct series with selectivity over Leishmania NMT. We believe that release of results from this study into the public domain will accelerate the discovery of NMT inhibitors to treat malaria and leishmaniasis. Our screening initiative is another example of how a tripartite partnership involving pharmaceutical industries, academic institutions and governmental/non-governmental organisations such as Medical Research Council and Wellcome Trust can stimulate research for neglected diseases

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Control of star formation by supersonic turbulence

Understanding the formation of stars in galaxies is central to much of modern astrophysics. For several decades it has been thought that stellar birth is primarily controlled by the interplay between gravity and magnetostatic support, modulated by ambipolar diffusion. Recently, however, both observational and numerical work has begun to suggest that support by supersonic turbulence rather than magnetic fields controls star formation. In this review we outline a new theory of star formation relying on the control by turbulence. We demonstrate that although supersonic turbulence can provide global support, it nevertheless produces density enhancements that allow local collapse. Inefficient, isolated star formation is a hallmark of turbulent support, while efficient, clustered star formation occurs in its absence. The consequences of this theory are then explored for both local star formation and galactic scale star formation. (ABSTRACT ABBREVIATED)Comment: Invited review for "Reviews of Modern Physics", 87 pages including 28 figures, in pres