Interference of the T cell and antigen-presenting cell costimulatory pathway using CTLA4-Ig (abatacept) prevents Staphylococcal enterotoxin B pathology

Abstract Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds the receptors in the APC/T cell synapse and causes increased proliferation of T cells and a cytokine storm syndrome in vivo. Exposure to the toxin can be lethal and cause significant pathology in humans. The lack of effective therapies for SEB exposure remains an area of concern, particularly in scenarios of acute mass casualties. We hypothesized that blockade of the T cell costimulatory signal by the CTLA4-Ig synthetic protein (abatacept) could prevent SEB-dependent pathology. In this article, we demonstrate mice treated with a single dose of abatacept 8 h post SEB exposure had reduced pathology compared with control SEB-exposed mice. SEB-exposed mice showed significant reductions in body weight between days 4 and 9, whereas mice exposed to SEB and also treated with abatacept showed no weight loss for the duration of the study, suggesting therapeutic mitigation of SEB-induced morbidity. Histopathology and magnetic resonance imaging demonstrated that SEB mediated lung damage and edema, which were absent after treatment with abatacept. Analysis of plasma and lung tissues from SEB-exposed mice treated with abatacept demonstrated significantly lower levels of IL-6 and IFN-γ (p &amp;lt; 0.0001), which is likely to have resulted in less pathology. In addition, exposure of human and mouse PBMCs to SEB in vitro showed a significant reduction in levels of IL-2 (p &amp;lt; 0.0001) after treatment with abatacept, indicating that T cell proliferation is the main target for intervention. Our findings demonstrate that abatacept is a robust and potentially credible drug to prevent toxic effects from SEB exposure.</jats:p

Searching for Gravitational Waves from the Inspiral of Precessing Binary Systems: Astrophysical Expectations and Detection Efficiency of "Spiky'' Templates

Relativistic spin-orbit and spin-spin couplings has been shown to modify the gravitational waveforms expected from inspiraling binaries with a black hole and a neutron star. As a result inspiral signals may be missed due to significant losses in signal-to-noise ratio, if precession effects are ignored in gravitational-wave searches. We examine the sensitivity of the anticipated loss of signal-to-noise ratio on two factors: the accuracy of the precessing waveforms adopted as the true signals and the expected distributions of spin-orbit tilt angles, given the current understanding of their physical origin. We find that the results obtained using signals generated by approximate techniques are in good agreement with the ones obtained by integrating the 2PN equations. This shows that a complete account of all high-order post-Newtonian effects is usually not necessary for the determination of detection efficiencies. Based on our current astrophysical expectations, large tilt angles are not favored and as a result the decrease in detection rate varies rather slowly with respect to the black hole spin magnitude and is within 20--30% of the maximum possible values.Comment: 7 fig., accepted by Phys. Rev. D Minor modification

Observational constraints on the neutron star mass distribution

Radio observations of neutron star binary pulsar systems have constrained strongly the masses of eight neutron stars. Assuming neutron star masses are uniformly distributed between lower and upper bounds $m_l$ and $m_u$, the observations determine with 95\% confidence that $1.01 < m_l/\text{M}_\odot < 1.34$ and $1.43 < m_u/\text{M}_\odot < 1.64$. These limits give observational support to neutron star formation scenarios that suggest that masses should fall predominantly in the range $1.3<m/\text{M}_\odot<1.6$, and will also be important in the interpretation of binary inspiral observations by the Laser Interferometer Gravitational-wave Observatory.Comment: Postscript, 4 pages, NU-GR-

Cosmological post-Newtonian expansions to arbitrary order

We prove the existence of a large class of one parameter families of solutions to the Einstein-Euler equations that depend on the singular parameter \ep=v_T/c (0<\ep < \ep_0), where $c$ is the speed of light, and $v_T$ is a typical speed of the gravitating fluid. These solutions are shown to exist on a common spacetime slab M\cong [0,T)\times \Tbb^3, and converge as \ep \searrow 0 to a solution of the cosmological Poisson-Euler equations of Newtonian gravity. Moreover, we establish that these solutions can be expanded in the parameter \ep to any specified order with expansion coefficients that satisfy \ep-independent (nonlocal) symmetric hyperbolic equations

Deformation of the Planetary Orbits Caused by the Time Dependent Gravitational Potential in the Universe

In the paper are studied the deformations of the planetary orbits caused by the time dependent gravitational potential in the universe. It is shown that the orbits are not axially symmetric and the time dependent potential does not cause perihelion precession. It is found a simple formula for the change of the orbit period caused by the time dependent gravitational potential and it is tested for two binary pulsars.Comment: 7 page

Modelling of monopile-footing foundation system for offshore structures

While monopiles have proven to be an economically sound foundation solution for wind turbines, especially in relatively shallow water, their installation in deeper water and in hard ground may require a more complex foundation design in order to satisfy the loading conditions. One approach is that foundation systems are developed which combine several foundation elements to create a ‘hybrid’ system. In this way it is possible to develop a foundation system which is more efficient for the combination of vertical and lateral loads associated with wind turbines while maintaining the efficiency and simplicity of the design. Previous studies have reported the results of single gravity tests of the hybrid system where the benefits of adding the footing to the pile are illustrated. This paper presents experimental results on the performance of skirted and unskirted monopile-footings. A simplified design approach based on conventional lateral pile analysis is presented

On the positive mass theorem for manifolds with corners

We study the positive mass theorem for certain non-smooth metrics following P. Miao's work. Our approach is to smooth the metric using the Ricci flow. As well as improving some previous results on the behaviour of the ADM mass under the Ricci flow, we extend the analysis of the zero mass case to higher dimensions.Comment: 21 pages, incorporated referee's comment

Optimum Placement of Post-1PN GW Chirp Templates Made Simple at any Match Level via Tanaka-Tagoshi Coordinates

A simple recipe is given for constructing a maximally sparse regular lattice of spin-free post-1PN gravitational wave chirp templates subject to a given minimal match constraint, using Tanaka-Tagoshi coordinates.Comment: submitted to Phys. Rev.

Cutoff Latitudes of Solar Proton Events Measured by GPS Satellites

Solar energetic particles (SEPs), one of the main causes of particle radiation in interplanetary space, can disrupt radio communication, induce spacecraft failures and change the heating and cooling rates in the atmosphere among others. To investigate the impact of SEPs and more specifically solar proton events (SPEs), we established a cutoff latitude database based on energetic particle data from Combined X-ray Dosimeters (CXDs) on board the Global Positioning System (GPS) spacecraft. Introducing a novel normalization method involving proton fluxes from the Geostationary Operational Environmental Satellites enabled us to include the CXD data from its introduction (2001) onwards. The database contains 5714 cutoff latitudes divided over six energies between 18 and 115 MeV which occur during 58 SPEs from 2001 to 2015. Based on the database, a cutoff latitude parameterization as a function of solar wind dynamic pressure and geomagnetic indices Kp and Dst is created for each energy. Moreover, comparisons to previous studies on energetic particle data from the Polar Orbiting Environmental Satellites have been performed to put the GPS data into perspective. A 1–2° poleward offset is found for the GPS based cutoff latitude models, for which several causes are discussed. Furthermore, the limitation of GPS data to geomagnetic latitudes above 60° should be considered. All in all, the usage of the long time span of GPS data in this study combined with its recent release (2016) opens up a new range of studies involving GPS energetic particle data such as investigating long-term trends with respect to our solar cycle or magnetospheric trends.publishedVersio