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

From quantum trajectories to classical orbits

Recently it has been shown that the evolution of open quantum systems may be ``unraveled'' into individual ``trajectories,'' providing powerful numerical and conceptual tools. In this letter we use quantum trajectories to study mesoscopic systems and their classical limit. We show that in this limit, Quantum Jump (QJ) trajectories approach a diffusive limit very similar to the Quantum State Diffusion (QSD) unraveling. The latter follows classical trajectories in the classical limit. Hence, both unravelings show the rise of classical orbits. This is true for both regular and chaotic systems (which exhibit strange attractors).Comment: 7 pages RevTeX 3.0 + 2 figures (postscript). Submitted to Physical Review Letter

Improving professional psychological practice through an increased repertoire of research methodologies : illustrated by the development of MOL.

Mental health problems present an increasing global disease burden making the development of effective and efficient psychological treatments an urgent public health priority. Despite the continued proliferation of treatments and large numbers of randomized controlled trials (RCTs), evidence suggests that pre-post effect sizes have been decreasing over time not increasing. Promoting RCTs as a gold standard of evidence has not been a useful strategy for advancing progress in the development of increasingly effective and efficient psychological treatments and has, in fact, created a divide between research and practice in professional psychology. To close this divide, other methodologies are needed that can assist in the rigorous development and evaluation of treatments in routine clinical practice. We outline some of the problems with using RCTs as the sole means of generating evidence for treatment effectiveness and efficiency and we use the development and evaluation of a transdiagnostic cognitive therapy to illustrate an alternative way of accumulating evidence through a much closer connection between research and practice. Ultimately, including other methodologies alongside RCTs that combine research and practice more seamlessly, will produce treatments of greater effectiveness and efficiency and help to reduce the global burden of mental health problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved

Lines on projective varieties and applications

The first part of this note contains a review of basic properties of the variety of lines contained in an embedded projective variety and passing through a general point. In particular we provide a detailed proof that for varieties defined by quadratic equations the base locus of the projective second fundamental form at a general point coincides, as a scheme, with the variety of lines. The second part concerns the problem of extending embedded projective manifolds, using the geometry of the variety of lines. Some applications to the case of homogeneous manifolds are included.Comment: 15 pages. One example removed; one remark and some references added; typos correcte

Exact spectra, spin susceptibilities and order parameter of the quantum Heisenberg antiferromagnet on the triangular lattice

Exact spectra of periodic samples are computed up to $N=36$. Evidence of an extensive set of low lying levels, lower than the softest magnons, is exhibited. These low lying quantum states are degenerated in the thermodynamic limit; their symmetries and dynamics as well as their finite-size scaling are strong arguments in favor of N\'eel order. It is shown that the N\'eel order parameter agrees with first-order spin-wave calculations. A simple explanation of the low energy dynamics is given as well as the numerical determinations of the energies, order parameter and spin susceptibilities of the studied samples. It is shown how suitable boundary conditions, which do not frustrate N\'eel order, allow the study of samples with $N=3p+1$ spins. A thorough study of these situations is done in parallel with the more conventional case $N=3p$.Comment: 36 pages, REVTeX 3.0, 13 figures available upon request, LPTL preprin

Realistic Equations of State for the Primeval Universe

Early universe equations of state including realistic interactions between constituents are built up. Under certain reasonable assumptions, these equations are able to generate an inflationary regime prior to the nucleosynthesis period. The resulting accelerated expansion is intense enough to solve the flatness and horizon problems. In the cases of curvature parameter \kappa equal to 0 or +1, the model is able to avoid the initial singularity and offers a natural explanation for why the universe is in expansion.Comment: 32 pages, 5 figures. Citations added in this version. Accepted EPJ

Lagrangian Curves in a 4-dimensional affine symplectic space

Lagrangian curves in R4 entertain intriguing relationships with second order deformation of plane curves under the special affine group and null curves in a 3-dimensional Lorentzian space form. We provide a natural affine symplectic frame for Lagrangian curves. It allows us to classify La- grangrian curves with constant symplectic curvatures, to construct a class of Lagrangian tori in R4 and determine Lagrangian geodesic

Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.

Despite being a critical molecule in the brain, mass spectrometry imaging (MSI) of cholesterol has been under-reported compared to other lipids due to the difficulty in ionizing the sterol molecule. In the present work, we have employed an on-tissue enzyme-assisted derivatization strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific structures of the mouse brain, in a model of Niemann-Pick type C1 disease, and during brain development. MSI revealed that in the adult mouse, cholesterol is the highest in the pons and medulla and how its distribution changes during development. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience