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

Robust signatures in the current-voltage characteristics of DNA molecules oriented between two graphene nanoribbon electrodes

In this work we numerically calculate the electric current through three kinds of DNA sequences (telomeric, \lambda-DNA, and p53-DNA) described by different heuristic models. A bias voltage is applied between two zig-zag edged graphene contacts attached to the DNA segments, while a gate terminal modulates the conductance of the molecule. The calculation of current is performed by integrating the transmission function (calculated using the lattice Green's function) over the range of energies allowed by the chemical potentials. We show that a telomeric DNA sequence, when treated as a quantum wire in the fully coherent low-temperature regime, works as an excellent semiconductor. Clear steps are apparent in the current-voltage curves of telomeric sequences and are present independent of lengths and sequence initialisation at the contacts. The current-voltage curves suggest the existence of stepped structures independent of length and sequencing initialisation at the contacts. We also find that the molecule-electrode coupling can drastically influence the magnitude of the current. The difference between telomeric DNA and other DNA, such as \lambda-DNA and DNA for the tumour suppressor p53, is particularly visible in the length dependence of the current

Rising gasoline prices increase new motorcycle sales and fatalities

Background: We examined whether sales of new motorcycles was a mechanism to explain the relationship between motorcycle fatalities and gasoline prices. Methods: The data came from the Motorcycle Industry Council, Energy Information Administration and Fatality Analysis Reporting System for 1984–2009. Autoregressive integrated moving average (ARIMA) regressions estimated the effect of inflation-adjusted gasoline price on motorcycle sales and logistic regressions estimated odds ratios (ORs) between new and old motorcycle fatalities when gasoline prices increase. Results: New motorcycle sales were positively correlated with gasoline prices (r = 0.78) and new motorcycle fatalities (r = 0.92). ARIMA analysis estimated that a US$1 increase in gasoline prices would result in 295,000 new motorcycle sales and, consequently, 233 new motorcycle fatalities. Compared to crashes on older motorcycle models, those on new motorcycles were more likely to be young riders, occur in the afternoon, in clear weather, with a large engine displacement, and without alcohol involvement. Riders on new motorcycles were more likely to be in fatal crashes relative to older motorcycles (OR 1.14, 95 % confidence interval (CI) 1.02–1.28) when gasoline prices increase. Conclusions: Our findings suggest that, in response to increasing gasoline prices, people tend to purchase new motorcycles, and this is accompanied with significantly increased crash risk. There are several policy mechanisms that can be used to lower the risk of motorcycle crash injuries through the mechanism of gas prices and motorcycle sales such as raising awareness of motorcycling risks, enhancing licensing and testing requirements, limiting motorcycle power-to-weight ratios for inexperienced riders, and developing mandatory training programs for new riders

Evidence for a supermassive object in the nucleus of the galaxy M87 from SIT and CCD area photometry

Two-dimensional SIT and CCD detectors have been used to measure the surface brightness of the peculiar elliptical radio galaxy M87. Measurements were made in three broad-band colors (B, V, and R) to a distance of 80" from the nucleus, with 1" spatial resolution and photometric accuracy of the order of 1%. The data are given in some detail and are compared with earlier photographic results. The most obvious feature of the data is a bright, barely resolved central luminosity spike, which is not seen in similar data on other nearby normal ellipticals. Also, attempts to fit isothermal or King models away from the nuclear spike show additional excess luminosity in the central regions of the galaxy (r 60. All of the existing data is well fitted by a King model containing a central black hole of mass M = 3 x 10^9 M_⊙ and a point luminosity source. While such a model is not uniquely required by the data, it is perhaps the most plausible of several possible models considered. At present, M87 is probably the best case for a hypothetical massive black hole in a galaxy nucleus

Artificial turf: chemical flux and development of silicone wristband partitioning coefficients

This work uses passive samplers to identify PAHs and OPAHs not previously associated with artificial turf, and to provide the first quantitative measure of in situ flux of semi-volatile contaminants on artificial turf fields. Both air (1.5-m height) and turf air (immediately above turf surface) were sampled using two sampling materials: low-density polyethylene and silicone. Utilizing a broad targeted screen, we assess both artificial turf and samples of crumb rubber for over 1530 chemicals including pesticides, phthalates, and personal care products. We report the presence of 25 chemicals that have not yet been reported in artificial turf literature, including some with known human effects. The samplers were also quantitatively analyzed for polycyclic aromatic hydrocarbons yielding gas-phase concentrations at breathing height and surface level—the first such report on an artificial turf outdoor field. Turf pore-air and air chemicals were highly correlated at all sites, and particularly at the recently installed indoor site. Flux of chemicals between air and turf surface appear to follow field age although more research is needed to confirm this trend. The thermal extraction process and silicone passive samplers used are suitable for larger-scale environmental sampling campaigns that aim for less solvent and sample processing. By co-deploying silicone passive samplers and conventional low-density polyethylene, partitioning coefficients are derived that can be used for future silicone passive air sampling environmental assessment. This study provides an initial demonstration that passive samplers can be used to quantify volatile and semi-volatile organic chemicals from artificial turf.publishedVersio

Neutrino production through hadronic cascades in AGN accretion disks

We consider the production of neutrinos in active galactic nuclei (AGN) through hadronic cascades. The initial, high energy nucleons are accelerated in a source above the accretion disk around the central black hole. From the source, the particles diffuse back to the disk and initiate hadronic cascades. The observable output from the cascade are electromagnetic radiation and neutrinos. We use the observed diffuse background X-ray luminosity, which presumably results {}from this process, to predict the diffuse neutrino flux close to existing limits from the Frejus experiment. The resulting neutrino spectrum is $E^{-2}$ down to the \GeV region. We discuss modifications of this scenario which reduce the predicted neutrino flux.Comment: 12 Pages, LaTeX, TK 92 0

A possible magnetar nature for IGR J16358-4726

We present detailed spectral and timing analysis of the hard X-ray transient IGR J16358-4726 using multisatellite archival observations. A study of the source flux time history over 6 yr suggests that lower luminosity transient outbursts can be occurring in intervals of at most 1 yr. Joint spectral fits of the higher luminosity outburst using simultaneous Chandra ACIS and INTEGRAL ISGRI data reveal a spectrum well described by an absorbed power-law model with a high-energy cutoff plus an Fe line. We detected the 1.6 hr pulsations initially reported using Chandra ACIS also in the INTEGRAL ISGRI light curve and in subsequent XMM-Newton observations. Using the INTEGRAL data, we identified a spin-up of 94 s ( = 1.6 × 10-4), which strongly points to a neutron star nature for IGR J16358-4726. Assuming that the spin-up is due to disk accretion, we estimate that the source magnetic field ranges between 1013 and 1015 G, depending on its distance, possibly supporting a magnetar nature for IGR J16358-4726

The Prelude to and Aftermath of the Giant Flare of 2004 December 27: Persistent and Pulsed X-ray Properties of SGR 1806-20 from 1993 to 2005

On 2004 December 27, a highly-energetic giant flare was recorded from the magnetar candidate SGR 1806-20. In the months preceding this flare, the persistent X-ray emission from this object began to undergo significant changes. Here, we report on the evolution of key spectral and temporal parameters prior to and following this giant flare. Using the Rossi X-ray Timing Explorer, we track the pulse frequency of SGR 1806-20 and find that the spin-down rate of this SGR varied erratically in the months before and after the flare. Contrary to the giant flare in SGR 1900+14, we find no evidence for a discrete jump in spin frequency at the time of the December 27th flare (|dnu/nu| < 5 X 10^-6). In the months surrounding the flare, we find a strong correlation between pulsed flux and torque consistent with the model for magnetar magnetosphere electrodynamics proposed by Thompson, Lyutikov & Kulkarni (2002). As with the flare in SGR 1900+14, the pulse morphology of SGR 1806-20 changes drastically following the flare. Using the Chandra X-ray Observatory and other publicly available imaging X-ray detector observations, we construct a spectral history of SGR 1806-20 from 1993 to 2005. The usual magnetar persistent emission spectral model of a power-law plus a blackbody provides an excellent fit to the data. We confirm the earlier finding by Mereghetti et al. (2005) of increasing spectral hardness of SGR 1806-20 between 1993 and 2004. Contrary to the direct correlation between torque and spectral hardness proposed by Mereghetti et al., we find evidence for a sudden torque change that triggered a gradual hardening of the energy spectrum on a timescale of years. Interestingly, the spectral hardness, spin-down rate, pulsed, and phase-averaged of SGR 1806-20 all peak months before the flare epoch.Comment: 37 pages, 8 figures, 8 tables. Accepted for publication in ApJ. To appear in the Oct 20 2006 editio

Quarkonia and the Pole Mass

The pole mass of a heavy quark is ambiguous by an amount of order $\Lambda_{QCD}$. We show that the heavy-quark potential, $V(r)$, is similarly ambiguous, but that the total static energy, $2M_{pole}+V(r)$, is unambiguous when expressed in terms of a short-distance mass. This implies that the extraction of a short-distance mass from the quarkonium spectrum is free of an ambiguity of order $\Lambda_{QCD}$, in contrast with the pole mass.Comment: 6 pages, LateX. Minor revisions for publicatio