IL-10 Regulates Viral Lung Immunopathology during Acute Respiratory Syncytial Virus Infection in Mice

Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. Here we demonstrate that infection of BALB/c mice with respiratory syncytial virus (RSV) induced IL-10 production by CD4(+) and CD8(+) T cells in the airways at later time points (e.g. day 8); a proportion of these cells also co-produced IFN-γ. Furthermore, RSV infection of IL-10(−/−) mice resulted in more severe disease with enhanced weight loss, delayed recovery and greater cell infiltration of the respiratory tract without affecting viral load. In addition, IL-10(−/−) mice had a pronounced airway neutrophilia and heightened levels of pro-inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid. Notably, the proportion of lung T cells producing IFN-γ was enhanced, suggesting that IL-10 may act in an autocrine manner to dampen effector T cell responses. Similar findings were made in mice treated with anti-IL-10R antibody and infected with RSV. Therefore, IL-10 inhibits disease and inflammation in mice infected with RSV, especially during recovery from infection

Wake Development behind Paired Wings with Tip and Root Trailing Vortices: Consequences for Animal Flight Force Estimates

Recent experiments on flapping flight in animals have shown that a variety of unrelated species shed a wake behind left and right wings consisting of both tip and root vortices. Here we present an investigation using Particle Image Velocimetry (PIV) of the behaviour and interaction of trailing vortices shed by paired, fixed wings that simplify and mimic the wake of a flying animal with a non-lifting body. We measured flow velocities at five positions downstream of two adjacent NACA 0012 aerofoils and systematically varied aspect ratio, the gap between the wings (corresponding to the width of a non-lifting body), angle of attack, and the Reynolds number. The range of aspect ratios and Reynolds number where chosen to be relevant to natural fliers and swimmers, and insect flight in particular. We show that the wake behind the paired wings deformed as a consequence of the induced flow distribution such that the wingtip vortices convected downwards while the root vortices twist around each other. Vortex interaction and wake deformation became more pronounced further downstream of the wing, so the positioning of PIV measurement planes in experiments on flying animals has an important effect on subsequent force estimates due to rotating induced flow vectors. Wake deformation was most severe behind wings with lower aspect ratios and when the distance between the wings was small, suggesting that animals that match this description constitute high-risk groups in terms of measurement error. Our results, therefore, have significant implications for experimental design where wake measurements are used to estimate forces generated in animal flight. In particular, the downstream distance of the measurement plane should be minimised, notwithstanding the animal welfare constraints when measuring the wake behind flying animals

Relationship between temporomandibular joint dynamics and mouthguards: feasibility of a test method

A test system was developed establishing the feasibility of collecting biomechanical data as they relate to the use of mouthguards. Previous experimental studies have examined the physical and mechanical properties of mouthguard materials. This information has been used as a guide for establishing material standards and specifications for the fabrication of mouthguards, but it lacks the key biomechanical parameters required for a thorough mouthguard evaluation. The current study was designed to assess whether the impact force, condylar deflection, and strain superior to the temporomandibular joint region could be measured. A drop test was conducted on a cadaveric specimen to simulate loading at the chin point. To measure the force of impact, an accelerometer was attached to an impactor of known mass. High-speed biplanar (1000 frames per second) radiographs were used to determine condylar displacement. Radio-opaque markers were inserted into the bone at predetermined locations. Total displacement of these markers was determined in reference to anatomical landmarks. Strain gauges were attached to the mandible and skull to monitor the effects of the condyle impacting the base of the skull. Based on the data collected, forces were calculated by determining the product of the time-based acceleration and known mass. A measurable change in force between the mouthguards and the control (no mouthguard) was demonstrated. The average condylar displacement was successfully measured and indicated as an increase in total deflection for impacts conducted with mouthguards. Quantifiable strain was measured in the region above the mandibular fossa with and without the insertion of a mouthguard at all impact conditions. However, it was determined that additional gauges would provide critical data. Key biomechanical parameters for chin-point impacts were determined in the current study. The technique demonstrated that both displacement within the mandibular fossa and loading of the condyles occur during the impact event. Although the current study established a technique that can be used to examine the relationship between mouthguards and jaw-joint injuries, the role, if any, mouthguards play in the reduction of injuries cannot be established until a thorough analysis is completed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74031/1/j.1600-9657.2004.00213.x.pd

Revisiting Lynam's notion of the "fledgling psychopath": are HIA-CP children truly psychopathic-like?

<p>Abstract</p> <p>Background</p> <p>In his developmental model of emerging psychopathy, Lynam proposed that the "fledgling psychopath" is most likely to be located within a subgroup of children elevated in both hyperactivity/inattention/impulsivity (HIA) and conduct problems (CP). This approach has garnered some empirical support. However, the extent to which Lynam's model captures children who resemble psychopathy with regard to the core affective and interpersonal features remains unclear.</p> <p>Methods</p> <p>In the present study, we investigated this issue within a large community sample of youth (<it>N </it>= 617). Four groups (non-HIA-CP, HIA-only, CP-only, and HIA-CP), defined on the basis of teacher reports of the Strengths and Difficulties Questionnaire (SDQ), were compared with respect to parent-reported psychopathic-like traits and subjective emotional reactivity in response to unpleasant, emotionally-laden pictures from the International Affective Pictures System (IAPS).</p> <p>Results</p> <p>Results did not support Lynam's model. HIA-CP children did not appear most psychopathic-like on dimensions of callous-unemotional and narcissistic personality, nor did they report reduced emotional reactivity to the IAPS relative to the other children. Post-hoc regression analyses revealed a significant moderation such that elevated HIA weakened the association between CP and emotional underarousal.</p> <p>Conclusions</p> <p>Implications of these findings with regard to the development of psychopathy are discussed.</p

The Wasteland of Random Supergravities

We show that in a general \cal{N} = 1 supergravity with N \gg 1 scalar fields, an exponentially small fraction of the de Sitter critical points are metastable vacua. Taking the superpotential and Kahler potential to be random functions, we construct a random matrix model for the Hessian matrix, which is well-approximated by the sum of a Wigner matrix and two Wishart matrices. We compute the eigenvalue spectrum analytically from the free convolution of the constituent spectra and find that in typical configurations, a significant fraction of the eigenvalues are negative. Building on the Tracy-Widom law governing fluctuations of extreme eigenvalues, we determine the probability P of a large fluctuation in which all the eigenvalues become positive. Strong eigenvalue repulsion makes this extremely unlikely: we find P \propto exp(-c N^p), with c, p being constants. For generic critical points we find p \approx 1.5, while for approximately-supersymmetric critical points, p \approx 1.3. Our results have significant implications for the counting of de Sitter vacua in string theory, but the number of vacua remains vast.Comment: 39 pages, 9 figures; v2: fixed typos, added refs and clarification

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Relative finger position influences whether you can localize tactile stimuli

To investigate whether the relative positions of the fingers influence tactile localization, participants were asked to localize tactile stimuli applied to their fingertips. We measured the location and rate of errors for three finger configurations: fingers stretched out and together so that they are touching each other, fingers stretched out and spread apart maximally and fingers stretched out with the two hands on top of each other so that the fingers are interwoven. When the fingers contact each other, it is likely that the error rate to the adjacent fingers will be higher than when the fingers are spread apart. In particular, we reasoned that localization would probably improve when the fingers are spread. We aimed at assessing whether such adjacency was measured in external coordinates (taking proprioception into account) or on the body (in skin coordinates). The results confirmed that the error rate was lower when the fingers were spread. However, there was no decrease in error rate to neighbouring fingertips in the fingers spread condition in comparison with the fingers together condition. In an additional experiment, we showed that the lower error rate when the fingers were spread was not related to the continuous tactile input from the neighbouring fingers when the fingers were together. The current results suggest that information from proprioception is taken into account in perceiving the location of a stimulus on one of the fingertips