Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice

Experimental allergic encephalomyelitis (EAE)' is an autoimmune inflammatory demyelinating disease in the central nervous system (CNS) of animals immunized with myelin basic protein (MBP). The disease is directly mediated by Thelper cells that recognize MBP in the context ofclass II antigens of the MHC (1-3). In nude mice, a single clone of adoptively transferred MBP-reactive T helper cells can cause EAE (4), suggesting that these are the only T cells required for disease induction. As a prototypic model of T helper cell-mediated autoimmune disease, observations in EAE could likely be applicable to other T helper cell-mediated diseases such as murine lupus (5), thyroiditis (6), collagen arthritis (7), and adjuvant arthritis (8), as well as human autoimmune diseases. The MBP epitope is determined in part by the MHC. Using proteolytic peptide fragments of MBP, SJL/J (H-2s) and BIO.T(6R) (H-2q) mice were found to develop EAE to the COOH-terminal peptide of MBP, whereas PL/J (H-2u) and A/J (H-2k) mice developed EAE to the NH2-terminal peptide of MBP (9). Recently, by using synthetic peptides that overcome the difficulties of obtaining pure uncontaminated proteolytic peptides, a single T cell encephalitogenic epitope for PL/J mice has been identified . This epitope consists of the first nine NH2-terminal amino acid residues of MBP which must be acetylated at the a amino group to induce disease (10). Similar fine mapping of the encephalitogenic T cell epitope(s) for SJL/J mice has not been done, in part because of the large size of the COOH-terminal peptic fragment of MBP (residues 89-169 of rat MBP, reference 9). MouseMBP consists offour major forms due to differential RNA splicing of exons II and VI (11), resulting in molecular masses of 21, 18.5, 17.5, and 14 kD, in the relative amounts of 1 :10:3.5:35 . Since EAE can also be induced with the small form of rat MBP (14 kD), which has exons II and VI of the MBP gene deleted (12), the COOH-terminal encephalitogenic determinant for SJL/J mice must be present within a segment ofonly 42 amino acid residues . Consistent withthis notion is the observation that this peptide sequence is identical among the MBPs of several mammalian species, including mouse, rat, bovine, guinea pig, and porcine, all of which can induce EAE in SJL/mice (13, 14). To identify the SJL/J encephalitogenic T cell epitope(s), overlapping peptides to the COOH-terminal region ofthe small form of mouse MBP were synthesized. Two overlapping peptides encompassing an 18-amino acid region were found to elicit EAE in SJL/J mice. The finding of a single peptide region of MBP that is responsible for encephalitogenic T cell epitopes in SJL/J mice is analogous to that of the PL/J mice and has implications for the development of specific therapy for T cell-mediated autoimmune diseases

Effects of Cement Bases on the Stresses in Amalgam Restorations

A computerized dental model was used to study the stress induced in a Class 1 amalgam restoration when supported by bases of varying materials and thicknesses. Under the same load, the maximum tensile stresses and deftections in the amalgam restoration increased at least threefold with a zinc oxideeugenol base as compared with a ZnPO 4 cement base.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67330/2/10.1177_00220345750540010101.pd

Conditional evolution in single-atom cavity QED

We consider a typical setup of cavity QED consisting of a two-level atom interacting strongly with a single resonant electromagnetic field mode inside a cavity. The cavity is resonantly driven and the output undergoes continuous homodyne measurements. We derive an explicit expression for the state of the system conditional on a discrete photocount record. This expression takes a particularly simple form if the system is initially in the steady state. As a byproduct, we derive a general formula for the steady state that had been conjectured before in the strong driving limit.Comment: 15 pages, 1 postscript figure, added discussion of mode

Stress distribution within circumferential clasp arms

An analysis of stress distributions within circumferential clasp arms with various tapers, was undertaken in an effort to (1) determine the area of maximum stress concentration in both tapered and non-tapered clasps, and (2) to compare this point of maximum stress concentration with the area of frequent clasp breakage. The non-tapered clasp showed better distribution of stresses than the tapered clasps. The less favourable stress concentrations could result in eventual failure of the clasp when coupled with other factors such as porosities. The maximum shear stresses in the non-tapered clasp also were lower than those in the tapered clasps. As the taper of the clasp became more accentuated, the magnitude of the stresses increased and shifted towards the tip of the clasp. The maximum tensile stress calculated in a replica of a chromium–cobalt–nickel clasp was in the order of 34 MN/m 2 which is well below the ultimate tensile strength of the alloy. This observation leads to the proposal that failure of clasps is a function not only of design but also of other variables, such as porosities, surface irregularities, and fatigue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71998/1/j.1365-2842.1976.tb01453.x.pd

Coronal energy release by MHD avalanches. Effects on a structured, active region, multi-threaded coronal loop

A possible key element for large-scale energy release in the solar corona is an MHD kink instability in a single twisted magnetic flux tube. An initial helical current sheet fragments in a turbulent way into smaller-scale sheets, similarly to a nanoflare storm. As the loop expands in the radial direction during the relaxation process, an unstable loop can disrupt nearby stable loops and trigger an MHD avalanche. Exploratory investigations have been conducted in previous works with relatively simplified loop configurations. Here, we address a more realistic environment that comprehensively accounts for most of the physical effects involved in a stratified atmosphere, typical of an active region. The question is whether the avalanche process will be triggered, with what timescales, and how it will develop, as compared with the original, simpler approach. Three-dimensional MHD simulations describe the interaction of magnetic flux tubes, which have a stratified atmosphere, including chromospheric layers, the thin transition region to the corona, and the related transition from high-beta to low-beta regions. The model also includes the effects of thermal conduction and of optically thin radiation. Our simulations address the case where one flux tube among a few is twisted at the footpoints faster than its neighbours. We show that this flux tube becomes kink unstable first, in conditions in agreement with those predicted by analytical models. It rapidly involves nearby stable tubes, instigating significant magnetic reconnection and dissipation of energy as heat. The heating determines the development of chromospheric evaporation, while the temperature rises up to about 10 MK, close to microflares observations. This work confirms that avalanches are a viable mechanism for the storing and release of magnetic energy in plasma confined in closed coronal loops, as a result of photospheric motions.Comment: 16 pages, 16 figure

Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions

Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions

Collective Sideband Cooling in an Optical Ring Cavity

We propose a cavity based laser cooling and trapping scheme, providing tight confinement and cooling to very low temperatures, without degradation at high particle densities. A bidirectionally pumped ring cavity builds up a resonantly enhanced optical standing wave which acts to confine polarizable particles in deep potential wells. The particle localization yields a coupling of the degenerate travelling wave modes via coherent photon redistribution. This induces a splitting of the cavity resonances with a high frequency component, that is tuned to the anti-Stokes Raman sideband of the particles oscillating in the potential wells, yielding cooling due to excess anti-Stokes scattering. Tight confinement in the optical lattice together with the prediction, that more than 50% of the trapped particles can be cooled into the motional ground state, promise high phase space densities.Comment: 4 pages, 1 figur

On the suppression of the diffusion and the quantum nature of a cavity mode. Optical bistability; forces and friction in driven cavities

A new analytical method is presented here, offering a physical view of driven cavities where the external field cannot be neglected. We introduce a new dimensionless complex parameter, intrinsically linked to the cooperativity parameter of optical bistability, and analogous to the scaled Rabbi frequency for driven systems where the field is classical. Classes of steady states are iteratively constructed and expressions for the diffusion and friction coefficients at lowest order also derived. They have in most cases the same mathematical form as their free-space analog. The method offers a semiclassical explanation for two recent experiments of one atom trapping in a high Q cavity where the excited state is significantly saturated. Our results refute both claims of atom trapping by a quantized cavity mode, single or not. Finally, it is argued that the parameter newly constructed, as well as the groundwork of this method, are at least companions of the cooperativity parameter and its mother theory. In particular, we lay the stress on the apparently more fundamental role of our structure parameter.Comment: 24 pages, 7 figures. Submitted to J. Phys. B: At. Mol. Opt. Phy

3D MHD modeling of twisted coronal loops

We perform MHD modeling of a single bright coronal loop to include the interaction with a non-uniform magnetic field. The field is stressed by random footpoint rotation in the central region and its energy is dissipated into heating by growing currents through anomalous magnetic diffusivity that switches on in the corona above a current density threshold. We model an entire single magnetic flux tube, in the solar atmosphere extending from the high-beta chromosphere to the low-betacorona through the steep transition region. The magnetic field expands from the chromosphere to the corona. The maximum resolution is ~30 km. We obtain an overall evolution typical of loop models and realistic loop emission in the EUV and X-ray bands. The plasma confined in the fluxtube is heated to active region temperatures (~3 MK) after ~2/3 hr. Upflows from the chromosphere up to ~100 km/s fill the core of the fluxtube to densities above 109 cm-3. More heating is released in the low corona than the high corona and is finely structured both in space and time.Publisher PDFPeer reviewe