The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease.

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (alpha(M)beta(2), CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen-Mac-1 interaction in fibrinogen-gamma(390-396A) knock-in mice or pharmacologically impeding fibrinogen-Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (gamma(377-395)) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen-Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the gamma(377-395) fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation

WASP-47: A HOT JUPITER SYSTEM WITH TWO ADDITIONAL PLANETS DISCOVERED BY K2

Using new data from the K2 mission, we show that WASP-47, a previously known hot Jupiter host, also hosts two additional transiting planets: a Neptune-sized outer planet and a super-Earth inner companion. We measure planetary properties from the K2 light curve and detect transit timing variations (TTVs), confirming the planetary nature of the outer planet. We performed a large number of numerical simulations to study the dynamical stability of the system and to find the theoretically expected TTVs. The theoretically predicted TTVs are in good agreement with those observed, and we use the TTVs to determine the masses of two planets, and place a limit on the third. The WASP-47 planetary system is important because companion planets can both be inferred by TTVs and are also detected directly through transit observations. The depth of the hot Jupiter's transits make ground-based TTV measurements possible, and the brightness of the host star makes it amenable for precise radial velocity measurements. The system serves as a Rosetta Stone for understanding TTVs as a planet detection technique

Capillary micromechanics: Measuring the elasticity of microscopic soft objects

We present a simple method for accessing the elastic properties of microscopic deformable particles. This method is based on measuring the pressure-induced deformation of soft particles as they are forced through a tapered glass microcapillary. It allows us to determine both the compressive and the shear modulus of a deformable object in one single experiment. Measurements on a model system of poly-acrylamide microgel particles exhibit excellent agreement with measurements on bulk gels of identical composition. Our approach is applicable over a wide range of mechanical properties and should thus be a valuable tool for the characterization of a variety of soft and biological materials

Search for the QCD Critical Point: Higher Moments of Net-proton Multiplicity Distributions

Higher moments of event-by-event net-proton multiplicity distributions have been applied to search for the QCD critical point. Model results are used to provide a baseline for this search. The measured moment products, $\kappa\sigma^2$ and $S\sigma$ of net-proton distributions, which are directly connected to the thermodynamical baryon number susceptibility ratio in Lattice QCD and Hadron Resonance Gas (HRG) model, are compared to the transport and thermal model results. We argue that a non-monotonic dependence of $\kappa \sigma^2$ and $S \sigma$ as a function of beam energy can be used to search for the QCD critical point.Comment: 7 pages, 3 figures. CPOD 2010 Proceeding

The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (αMβ2, CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen–Mac-1 interaction in fibrinogen-γ390-396A knock-in mice or pharmacologically impeding fibrinogen–Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (γ377-395) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen–Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the γ377-395 fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation

Completing Natural Inflation

If the inflaton is a pseudo-scalar axion, the axion shift symmetry can protect the flatness of its potential from too large radiative corrections. This possibility, known as natural inflation, requires an axion scale which is greater than the (reduced) Planck scale. It is unclear whether such a high value is compatible with an effective field theoretical description, and if the global axionic symmetry survives quantum gravity effects. We propose a mechanism which provides an effective large axion scale, although the original one is sub-Planckian. The mechanism is based on the presence of two axions, with a potential provided by two anomalous gauge groups. The effective large axion scale is due to an almost exact symmetry between the couplings of the axions to the anomalous groups. We also comment on a possible implementation in heterotic string theory.Comment: 9 pages, 1 figur

Super-star clusters versus OB associations

Super Star Clusters (Mecl > 10^5 Msol) are the largest stellar nurseries in our local Universe, containing hundreds of thousands to millions of young stars within a few light years. Many of these systems are found in external galaxies, especially in pairs of interacting galaxies, and in some dwarf galaxies, but relatively few in disk galaxies like our own Milky Way. We show that a possible explanation for this difference is the presence of shear in normal spiral galaxies which impedes the formation of the very large and dense super star clusters but prefers the formation of loose OB associations possibly with a less massive cluster at the center. In contrast, in interacting galaxies and in dwarf galaxies, regions can collapse without having a large-scale sense of rotation. This lack of rotational support allows the giant clouds of gas and stars to concentrate into a single, dense and gravitationally bound system.Comment: uses emulateapj-rtx4.cls, 7 pages, 6 figures, 2 tables, accepted for publication by Ap

Are local wind power resources well estimated?

Planning and financing of wind power installations require very importantly accurate resource estimation in addition to a number of other considerations relating to environment and economy. Furthermore, individual wind energy installations cannot in general be seen in isolation. It is well known that the spacing of turbines in wind farms is critical for maximum power production. It is also well established that the collective effect of wind turbines in large wind farms or of several wind farms can limit the wind power extraction downwind. This has been documented by many years of production statistics. For the very large, regional sized wind farms, a number of numerical studies have pointed to additional adverse changes to the regional wind climate, most recently by the detailed studies of Adams and Keith [1]. They show that the geophysical limit to wind power production is likely to be lower than previously estimated. Although this problem is of far future concern, it has to be considered seriously. In their paper they estimate that a wind farm larger than 100 km ^2 is limited to about 1 W m ^-2 . However, a 20 km ^2 off shore farm, Horns Rev 1, has in the last five years produced 3.98 W m ^-2  [5]. In that light it is highly unlikely that the effects pointed out by [1] will pose any immediate threat to wind energy in coming decades. Today a number of well-established mesoscale and microscale models exist for estimating wind resources and design parameters and in many cases they work well. This is especially true if good local data are available for calibrating the models or for their validation. The wind energy industry is still troubled by many projects showing considerable negative discrepancies between calculated and actually experienced production numbers and operating conditions. Therefore it has been decided on a European Union level to launch a project, ‘The New European Wind Atlas’, aiming at reducing overall uncertainties in determining wind conditions. The project is structured around three areas of work, to be implemented in parallel. One of the great challenges to the project is the application of mesoscale models for wind resource calculation, which is by no means a simple matter [3]. The project will use global reanalysis data as boundary conditions. These datasets, which are time series of the large-scale meteorological situation covering decades, have been created by assimilation of measurement data from around the globe in a dynamical consistent fashion using large-scale numerical models. For wind energy, the application of the reanalysis datasets is as a long record of the large-scale wind conditions. The large-scale reanalyses are performed in only a few global weather prediction centres using models that have been developed over many years, and which are still being developed and validated and are being used in operational services. Mesoscale models are more diverse, but nowadays quite a number have a proven track record in applications such as regional weather prediction and also wind resource assessment. There are still some issues, and use of model results without proper validation may lead to gross errors. For resource assessment it is necessary to include direct validation with in situ observed wind data over sufficiently long periods. In doing so, however, the mesoscale model output must be downscaled using some microscale physical or empirical/statistical model. That downscaling process is not straightforward, and the microscale models themselves tend to disagree in some terrain types as shown by recent blind tests [4]. All these ‘technical’ details and choices, not to mention the model formulation itself, the numerical schemes used, and the effective spatial and temporal resolution, can have a significant impact on the results. These problems, as well as the problem of how uncertainties are propagated through the model chain to the calculated wind resources, are central in the work with the New European Wind Atlas. The work of [1] shows that when wind energy has been implemented on a very massive scale, it will affect the power production from entire regions and that has to be taken into account. References [1] Adams A S and Keith D W 2013 Are global wind power resource estimates overstated? Environ. Res. Lett. 8 015021 [2] 2011 A New EU Wind Energy Atlas: Proposal for an ERANET+ Project (Produced by the TPWind Secretariat) Nov. [3] Petersen E L Troen I 2012 Wind conditions and resource assessment WIREs Energy Environ. 1 206–17 [4] Bechmann A, Sørensen N N, Berg J, Mann J Rethore P-E 2011 The Bolund experiment, part II: blind comparison of microscale flow models Boundary-Layer Meteorol. 141 245–71 [5] http://www.lorc.dk/offshore-wind-farms-map/horns-rev-1 http://www.ens.d

Virtual Machine Support for Many-Core Architectures: Decoupling Abstract from Concrete Concurrency Models

The upcoming many-core architectures require software developers to exploit concurrency to utilize available computational power. Today's high-level language virtual machines (VMs), which are a cornerstone of software development, do not provide sufficient abstraction for concurrency concepts. We analyze concrete and abstract concurrency models and identify the challenges they impose for VMs. To provide sufficient concurrency support in VMs, we propose to integrate concurrency operations into VM instruction sets. Since there will always be VMs optimized for special purposes, our goal is to develop a methodology to design instruction sets with concurrency support. Therefore, we also propose a list of trade-offs that have to be investigated to advise the design of such instruction sets. As a first experiment, we implemented one instruction set extension for shared memory and one for non-shared memory concurrency. From our experimental results, we derived a list of requirements for a full-grown experimental environment for further research