Dissecting interferon-induced transcriptional programs in human peripheral blood cells

Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1) compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs) elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2) characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes) to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings

Collaborative working within UK NHS secondary care and across sectors for COPD and the impact of peer review : qualitative findings from the UK National COPD Resources and Outcomes Project

Introduction: We investigated the effects on collaborative work within the UK National Health Service (NHS) of an intervention for service quality improvement: informal, structured, reciprocated, multidisciplinary peer review with feedback and action plans. The setting was care for chronic obstructive pulmonary disease (COPD). Theory and methods: We analysed semi-structured interviews with 43 hospital respiratory consultants, nurses and general managers at 24 intervention and 11 control sites, as part of a UK randomised controlled study, the National COPD Resources and Outcomes Project (NCROP), using Scott’s conceptual framework for action (inter-organisational, intra-organisational, inter-professional and inter-individual). Three areas of care targeted by NCROP involved collaboration across primary and secondary care. Results: Hospital respiratory department collaborations with commissioners and hospital managers varied. Analysis suggested that this is related to team responses to barriers. Clinicians in unsuccessful collaborations told ‘atrocity stories’ of organisational, structural and professional barriers to service improvement. The others removed barriers by working with government and commissioner agendas to ensure continued involvement in patients’ care. Multidisciplinary peer review facilitated collaboration between participants, enabling them to meet, reconcile differences and exchange ideas across boundaries. Conclusions: The data come from the first randomised controlled trial of organisational peer review, adding to research into UK health service collaborative work, which has had a more restricted focus on inter-professional relations. NCROP peer review may only modestly improve collaboration but these data suggest it might be more effective than top-down exhortations to change when collaboration both across and within organisations is required

Phase Transitions from Saddles of the Potential Energy Landscape

The relation between saddle points of the potential of a classical many-particle system and the analyticity properties of its thermodynamic functions is studied. For finite systems, each saddle point is found to cause a nonanalyticity in the Boltzmann entropy, and the functional form of this nonanalytic term is derived. For large systems, the order of the nonanalytic term increases unboundedly, leading to an increasing differentiability of the entropy. Analyzing the contribution of the saddle points to the density of states in the thermodynamic limit, our results provide an explanation of how, and under which circumstances, saddle points of the potential energy landscape may (or may not) be at the origin of a phase transition in the thermodynamic limit. As an application, the puzzling observations by Risau-Gusman et al. on topological signatures of the spherical model are elucidated.Comment: 5 pages, no figure

Is the electrostatic force between a point charge and a neutral metallic object always attractive?

We give an example of a geometry in which the electrostatic force between a point charge and a neutral metallic object is repulsive. The example consists of a point charge centered above a thin metallic hemisphere, positioned concave up. We show that this geometry has a repulsive regime using both a simple analytical argument and an exact calculation for an analogous two-dimensional geometry. Analogues of this geometry-induced repulsion can appear in many other contexts, including Casimir systems.Comment: 7 pages, 7 figure

Measurement of mutual inductance from frequency dependence of impedance of AC coupled circuit using digital dual-phase lock-in amplifier

We present a simple method to determine the mutual inductance $M$ between two coils in a coupled AC circuit by using a digital dual-phase lock-in amplifier. The frequency dependence of the real and imaginary parts is measured as the coupling constant is changed. The mutual inductance $M$ decreases as the distance $d$ between the centers of coils is increased. We show that the coupling constant is proportional to $d^{-n}$ with an exponent $n$ ($\approx$ 3). This coupling is similar to that of two magnetic moments coupled through a dipole-dipole interaction.Comment: 9 pages, 10 figures, Fig.1 is corrected, figures in png files, short version is published in Am. J. Phys. 76, (2008) 12

Orbitally excited and hybrid mesons from the lattice

We discuss in general the construction of gauge-invariant non-local meson operators on the lattice. We use such operators to study the $P$- and $D$-wave mesons as well as hybrid mesons in quenched QCD, with quark masses near the strange quark mass. The resulting spectra are compared with experiment for the orbital excitations. For the states produced by gluonic excitations (hybrid mesons) we find evidence of mixing for non-exotic quantum numbers. We give predictions for masses of the spin-exotic hybrid mesons with $J^{PC}=1^{-+},\ 0^{+-}$, and$2^{+-}$.Comment: 31 pages, LATEX, 8 postscript figures. Reference adde

Properties of galaxy dark matter halos from weak lensing

We present the results of a study of weak lensing by galaxies based on 45.5 deg$^2$ of $R_C$ band imaging data from the Red-Sequence Cluster Survey (RCS). We present the first weak lensing detection of the flattening of galaxy dark matter halos. We use a simple model in which the ellipticity of the halo is $f$ times the observed ellipticity of the lens. We find a best fit value of $f=0.77^{+0.18}_{-0.21}$, suggesting that the dark matter halos are somewhat rounder than the light distribution. The fact that we detect a significant flattening implies that the halos are well aligned with the light distribution. Given the average ellipticity of the lenses, this implies a halo ellipticity of $=0.33^{+0.07}_{-0.09}$, in fair agreement with results from numerical simulations of CDM. This result provides strong support for the existence of dark matter, as an isotropic lensing signal is excluded with 99.5% confidence. We also study the average mass profile around the lenses, using a maximum likelihood analysis. We consider two models for the halo mass profile: a truncated isothermal sphere (TIS) and an NFW profile. We adopt observationally motivated scaling relations between the lens luminosity and the velocity dispersion and the extent of the halo. The best fit NFW model yields a mass $M_{200}=(8.4\pm0.7\pm0.4)\times 10^{11} h^{-1} M_\odot$ and a scale radius $r_s=16.2^{+3.6}_{-2.9} h^{-1}$ kpc. This value for the scale radius is in excellent agreement with predictions from numerical simulations for a halo of this mass.Comment: Significantly revised version, accepted for publication in ApJ 11 pages, 6 figure

Effects of two contrasting canopy manipulations on growth and water use of London plane (Platanus x acerifolia) trees

Aims: Two contrasting canopy manipulations were compared to unpruned controls on London plane trees, to determine the effects on canopy regrowth, soil and leaf water relations. Methods: ‘Canopy reduction’, was achieved by removing the outer 30 % length of all major branches and ‘canopy thinning’, by removing 30 % of lateral branches arising from major branches. Results: Total canopy leaf areas recovered within two and three years of pruning for the canopy-thinned and reduced trees respectively. Canopy reduction increased mean leaf size, nitrogen concentration, canopy leaf area density and conserved soil moisture for up to 3 years, whereas canopy thinning had no effects. Another experiment compared more severe canopy reduction to unpruned trees. This produced a similar growth response to the previous experiment, but soil moisture was conserved nearer to the trunk. Analysis of 13C and 18O signals along with leaf water relations and soil moisture data suggested that lower boundary layer conductance within the canopy-reduced trees restricted tree water use, whereas for the canopy-thinned trees the opposite occurred. Conclusions: Only canopy reduction conserved soil moisture and this was due to a combination of reduced total canopy leaf area and structural changes in canopy architecture

Establishing norms with metanorms in distributed computational systems

Norms provide a valuable mechanism for establishing coherent cooperative behaviour in decentralised systems in which there is no central authority. One of the most influential formulations of norm emergence was proposed by Axelrod (Am Political Sci Rev 80(4):1095–1111, 1986). This paper provides an empirical analysis of aspects of Axelrod’s approach, by exploring some of the key assumptions made in previous evaluations of the model. We explore the dynamics of norm emergence and the occurrence of norm collapse when applying the model over extended durations . It is this phenomenon of norm collapse that can motivate the emergence of a central authority to enforce laws and so preserve the norms, rather than relying on individuals to punish defection. Our findings identify characteristics that significantly influence norm establishment using Axelrod’s formulation, but are likely to be of importance for norm establishment more generally. Moreover, Axelrod’s model suffers from significant limitations in assuming that private strategies of individuals are available to others, and that agents are omniscient in being aware of all norm violations and punishments. Because this is an unreasonable expectation , the approach does not lend itself to modelling real-world systems such as online networks or electronic markets. In response, the paper proposes alternatives to Axelrod’s model, by replacing the evolutionary approach, enabling agents to learn, and by restricting the metapunishment of agents to cases where the original defection is observed, in order to be able to apply the model to real-world domains . This work can also help explain the formation of a “social contract” to legitimate enforcement by a central authority