Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis.

CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy

Right to Serve, Right to Lead: Lives and Legacies of the USCT

This is a catalog for an exhibit that follows the evolution of African-American participation in the Civil War, from slaves, to contrabands, to soldiers of the United States Colored Troops (USCT), as well as the lives of black veterans beyond the war, and their ultimate military and social legacy. Using a variety of period items, it creates a narrative that stretches from the Antebellum Period to the current day. In doing so, the exhibit shows how black sacrifice on the battlefield redefined the war\u27s purpose throughout the divided nation, how Jim Crowe suppressed the memory of black participation after Reconstruction, and how the illustrious African-American military tradition left by the USCT endures to this day in their modern heirs

Grid cells on steeply sloping terrain: evidence for planar rather than volumetric encoding

Neural encoding of navigable space involves a network of structures centred on the hippocampus, whose neurons –place cells – encode current location. Input to the place cells includes afferents from the entorhinal cortex, which contains grid cells. These are neurons expressing spatially localised activity patches, or firing fields, that are evenly spaced across the floor in a hexagonal close-packed array called a grid. It is thought that grid cell grids function to enable the calculation of distances. The question arises as to whether this odometry process operates in three dimensions, and so we queried whether grids permeate three-dimensional space – that is, form a lattice – or whether they simply follow the environment surface. If grids form a three-dimensional lattice then a tilted floor should transect several layers of this lattice, resulting in interruption of the hexagonal pattern. We model this prediction with simulated grid lattices and show that on a 40-degree slope the firing of a grid cell should cover proportionally less of the surface, with smaller field size and fewer fields and reduced hexagonal symmetry. However, recording of grid cells as animals foraged on a 40-degree-tilted surface found that firing of grid cells was almost indistinguishable, in pattern or rate, from that on the horizontal surface, with if anything increased coverage and field number, and preserved field size. It thus appears unlikely that the sloping surface transected a lattice. However, grid cells on the slope displayed slightly degraded firing patterns, with reduced coherence and slightly reduced symmetry. These findings collectively suggest that the grid cell component of the metric representation of space is not fixed in absolute three-dimensional space but is influenced both by the surface the animal is on and by the relationship of this surface to the horizontal, supporting the hypothesis that the neural map of space is multi-planar rather than fully volumetric

Electromagnetic evaluation of the microstructure of grade 91 tubes/pipes

This paper assesses the feasibility of transferring a laboratory-based electromagnetic (EM) sensor technique, which has already proved sensitive to significant (e.g. phase balance) or subtle (e.g. number density of fine precipitates) microstructural changes in steel, to non-destructive evaluation of the microstructure of power generation components such as tubes/pipes. It has been found that Grade 91 steels, in different conditions representative of service entry, thermally aged or ex-service, can be distinguished using laboratory-based measurement systems on small machined cylindrical samples as well as by an industry deployment EM sensor system on full-diameter tube samples. The measurements for the tube samples follow the same trend as the machined cylindrical samples. The results indicate an industrial deployable sensor system can be used for sorting service-exposed or mis-heat-treated/mis-manufactured Grade 91 steel tubes/pipes from the correctly heat treated service-entry ones

Image-guided fluorescence tomography in head & neck surgical models

Clinical indications for fluorescence-guided surgery continue to expand, and are being spurred by the rapid development of new agents that improve biological targeting.1 There is a corresponding need to develop imaging systems that quantify fluorescence - not only at the tissue surface, but at depth. We have recently described an image-guided fluorescence tomography system that leverages geometric data from intraoperative cone-beam CT and surgical navigation,2 and builds on finite-element method software (NIRFAST) for diffuse optical tomography (DOT).3 DOT systems have most commonly been used for sub-surface inclusions buried within tissue (e.g., breast and neurological tumors). Here, we focus on inclusion models relevant to tumors infiltrating from the mucosal surface (an “iceberg” model), as is most often the case in head and neck cancer, where over 85% of tumors are squamous cell carcinoma.4 This work presents results from simulations, tissue-simulating anatomical phantoms, and animal studies involving infiltrative tumor models. The objective is to characterize system performance across a range of inclusion diameters, depths, and optical properties. For example, Fig. 1 shows a fluorescence reconstruction of a simulated tonsil tumor in an oral cavity phantom. Future clinical studies are necessary to assess in vivo performance and intraoperative workflow. Please click Additional Files below to see the full abstract

NGC 7582: The Prototype Narrow-Line X-ray Galaxy

NGC 7582 is a candidate prototype of the Narrow Line X-ray Galaxies (NLXGs) found in deep X-ray surveys. An ASCA observation shows the hard (> 3 keV) X-ray continuum of NGC 7582 drops 40% in ~6 ks, implying an AGN, while the soft band (< 3 keV) does not drop in concert with the hard continuum, requiring a separate component. The X-ray spectrum of NGC 7582 also shows a clear 0.5-2 keV soft (kT = 0.8 (+0.9,-0.3) keV or Gamma = 2.4 +/- 0.6; L(X) = 6 x 10**40 ergs s**-1) low--energy component, in addition to a heavily absorbed [N(H) = (6 +/- 2)\times 10**22 cm**-2 ] and variable 2-10 keV power law [Gamma = 0.7 (+0.3,-0.4); L(X) = (1.7-2.3) x 10**42 ergs s**-1]. This is one of the flattest 2-10 keV slopes in any AGN observed with ASCA. (The ROSAT HRI image of NGC 7582 further suggests extent to the SE.) These observations make it clear that the hard X-ray emission of NGC 7582, the most "narrow-line" of the NLXGs, is associated with an AGN. The strong suggestion is that all NLXGs are obscured AGNs, as hypothesized to explain the X-ray background spectral paradox. The separate soft X-ray component makes NGC 7582 (and by extension other NLXGs) detectable as a ROSAT source.Comment: text: Latex2e 10 pages, including 1 table, and 2 postscript figures via psfi

The Effects of Body Tempering on Force Production, Flexibility and Muscle Soreness in Collegiate Football Athletes

There has been limited research to explore the use of body tempering and when the use of this modality would be most appropriate. This study aimed to determine if a body tempering intervention would be appropriate pre-exercise by examining its effects on perceived soreness, range of motion (ROM), and force production compared to an intervention of traditional stretching. The subjects for this study were ten Division 1 (D1) football linemen from Sacred Heart University (Age: 19.9 ± 1.5 years, body mass: 130.9 ± 12.0 kg, height: 188.4 ± 5.1 cm, training age: 8.0 ± 3.5 years). Subjects participated in three sessions with the first session being baseline testing. The second and third sessions involved the participants being randomized to receive either the body tempering or stretching intervention for the second session and then receiving the other intervention the final week. Soreness using a visual analog scale (VAS), ROM, counter movement jump (CMJ) peak force and jump height, static jump (SJ) peak force and jump height, and isometric mid-thigh pull max force production were assessed. The results of the study concluded that body tempering does not have a negative effect on muscle performance but did practically reduce perceived muscle soreness. Since body tempering is effective at reducing soreness in athletes, it can be recommended for athletes as part of their pre-exercise warmup without negatively effecting isometric or dynamic force production

Limits and dynamics of stochastic neuronal networks with random heterogeneous delays

Realistic networks display heterogeneous transmission delays. We analyze here the limits of large stochastic multi-populations networks with stochastic coupling and random interconnection delays. We show that depending on the nature of the delays distributions, a quenched or averaged propagation of chaos takes place in these networks, and that the network equations converge towards a delayed McKean-Vlasov equation with distributed delays. Our approach is mostly fitted to neuroscience applications. We instantiate in particular a classical neuronal model, the Wilson and Cowan system, and show that the obtained limit equations have Gaussian solutions whose mean and standard deviation satisfy a closed set of coupled delay differential equations in which the distribution of delays and the noise levels appear as parameters. This allows to uncover precisely the effects of noise, delays and coupling on the dynamics of such heterogeneous networks, in particular their role in the emergence of synchronized oscillations. We show in several examples that not only the averaged delay, but also the dispersion, govern the dynamics of such networks.Comment: Corrected misprint (useless stopping time) in proof of Lemma 1 and clarified a regularity hypothesis (remark 1

Expansion of W 3(OH)

A direct measurement of the expansion of W 3(OH) is made by comparing Very Large Array images taken about 10 yr apart. The expansion is anisotropic with a typical speed of 3 to 5 km/s, indicating a dynamical age of only 2300 yr. These observations are inconsistent with either the freely expanding shell model or a simple bow shock model. The most favored model is a slowly expanding shell-like HII region, with either a fast rarefied flow or another less massive diffuse ionized region moving towards the observer. There is also a rapidly evolving source near the projected center of emission, perhaps related to the central star.Comment: LaTeX file, 28 pages, includes 8 figures. To appear in ApJ in December 10 (1998) issue. Also available at http://www.submm.caltech.edu/~kawamura/w3oh_pp.p