TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

Alpha-band rhythms in visual task performance: phase-locking by rhythmic sensory stimulation

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8-12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles

The parent analogy: a reassessment

According to the parent analogy, as a caretaker’s goodness, ability and intelligence increase, the likelihood that the caretaker will make arrangements for the attainment of future goods that are unnoticed or underappreciated by their dependents also increases. Consequently, if this analogy accurately represents our relationship to God, then we should expect to find many instances of inscrutable evil in the world. This argument in support of skeptical theism has recently been criticized by Dougherty. I argue that Dougherty’s argument is incomplete, for there are two plausible ways of construing the parent analogy’s conclusion. I supplement Dougherty’s case by offering a new argument against the parent analogy based on failed expectations concerning the amount of inscrutable evils encountered in the world. Consequently, there remains a significant empirical hurdle for skeptical theism to overcome if it is to maintain its status as a defeater for our reliability when tracking gratuitous evils.Publisher PDFPeer reviewe

A New Approach to Analyzing Patterns of Collaboration in Co-authorship Networks - Mesoscopic Analysis and Interpretation

This paper focuses on methods to study patterns of collaboration in co-authorship networks at the mesoscopic level. We combine qualitative methods (participant interviews) with quantitative methods (network analysis) and demonstrate the application and value of our approach in a case study comparing three research fields in chemistry. A mesoscopic level of analysis means that in addition to the basic analytic unit of the individual researcher as node in a co-author network, we base our analysis on the observed modular structure of co-author networks. We interpret the clustering of authors into groups as bibliometric footprints of the basic collective units of knowledge production in a research specialty. We find two types of coauthor-linking patterns between author clusters that we interpret as representing two different forms of cooperative behavior, transfer-type connections due to career migrations or one-off services rendered, and stronger, dedicated inter-group collaboration. Hence the generic coauthor network of a research specialty can be understood as the overlay of two distinct types of cooperative networks between groups of authors publishing in a research specialty. We show how our analytic approach exposes field specific differences in the social organization of research.Comment: An earlier version of the paper was presented at ISSI 2009, 14-17 July, Rio de Janeiro, Brazil. Revised version accepted on 2 April 2010 for publication in Scientometrics. Removed part on node-role connectivity profile analysis after finding error in calculation and deciding to postpone analysis

Development of PET Tracers of Glutamine Metabolism

The labeling of amino acids with positron-emitting radionuclides (such as fluorine-18) has been a widely used approach for the imaging of tumors as it often provides higher diagnostic accuracy than what is observed with [18F]FDG. In particular, PET tracers of glutamine metabolism have garnered significant attention in recent years. O-(2-[18F]fluoroethyl-L-tyrosine (18F-FET) is a promising PET tracer in this regard and is currently under investigation at Indiana University (IU) through an expanded access IND for patients with brain malignancies. Clinical production of 18F-FET at IU previously required the use of HPLC for purification, following the reaction of fluorine-18 with the precursor molecule for FET. While this method has been successful in removing undesirable impurities and byproducts, HPLC significantly increases synthesis time and is a common failure point in the synthesis of FET on our current radiochemistry module. To address this issue, we aimed to deploy a solid-phase-extraction (SPE) method for the purification of FET, thereby eliminating the need for HPLC purification. Several methods for the SPE purification of FET have been previously reported; however, none of these strategies afforded pure [18F]FET on our synthesis module, thus development of new methods was required.While several tracers capable of measuring different aspects of glutamine metabolism have been evaluated in both preclinical and clinical studies, there are metabolic liabilities that limit their utility and complicate data analysis. [18F]-4F-glutamine is one such tracer that has shown promise but has limitations due to undesirable metabolism in vivo. Herein we report our progress towards an improved synthesis of [18F]FET for ongoing clinical studies as well as our progress towards the development of a novel tracer that would address metabolic liabilities associated with currently available PET tracers of glutamine metabolism

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV

A search has been carried out for events in the channel p-barp --> gamma gamma jet jet. Such a signature can characterize the production of a non-standard Higgs boson together with a W or Z boson. We refer to this non-standard Higgs, having standard model couplings to vector bosons but no coupling to fermions, as a "bosonic Higgs." With the requirement of two high transverse energy photons and two jets, the diphoton mass (m(gamma gamma)) distribution is consistent with expected background. A 90(95)% C.L. upper limit on the cross section as a function of mass is calculated, ranging from 0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching ratios and corresponding new mass limit

Declining resilience of ecosystem functions under biodiversity loss

The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions-specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal