Transnuclear CD8 T cells specific for the immunodominant epitope Gra6 lower acute-phase Toxoplasma gondii burden.

We generated a CD8 T-cell receptor (TCR) transnuclear (TN) mouse specific to the Ld -restricted immunodominant epitope of GRA6 from Toxoplasma gondii as a source of cells to facilitate further investigation into the CD8 T-cell-mediated response against this pathogen. The TN T cells bound Ld -Gra6 tetramer and proliferated upon unspecific and peptide-specific stimulation. The TCR beta sequence of the Gra6-specific TN CD8 T cells is identical in its V- and J-region to the TCR-β harboured by a hybridoma line generated in response to Gra6 peptide. Adoptively transferred Gra6 TN CD8 T cells proliferated upon Toxoplasma infection in vivo and exhibited an activated phenotype similar to host CD8 T cells specific to Gra6. The brain of Toxoplasma-infected mice carried Gra6 TN cells already at day 8 post-infection. Both Gra6 TN mice as well as adoptively transferred Gra6 TN cells were able to significantly reduce the parasite burden in the acute phase of Toxoplasma infection. Overall, the Gra6 TN mouse represents a functional tool to study the protective and immunodominant specific CD8 T-cell response to Toxoplasma in both the acute and the chronic phases of infection

Crystal-Induced Inflammation: Studies of the Mechanism of Crystal-Membrane Interactions

Studies of the interactions of monosodium urate monohydrate (MSUM) crystals and calcium Pyrophosphate dihydrate triclinic (CPPD) crystals with biomembranes have been reviewed. Crystalmembrane binding and crystal-induced membranolysis have been studied using human erythrocytes as a model membrane system. The extent of MSUM-membrane binding was determined by incorporating a hydrophobic, fluorescent probe into the membranes, centrifugation to separate free membranes from membranes with bound crystals and quantitation of free membranes by measuring the total fluorescence intensity. The ability of MSUM and CPPD to hemolyse red cells was used as a measure of the membranolytic potential of the crystals. Fluorescence polarization studies showed that MSUM-membrane binding resulted in fluidization of the membrane. Cross-linking of the membrane proteins of the erythrocyte or the presence of divalent cations in the incubation medium inhibited MSUM induced hemolysis. These findings were explained by hypothesizing a pore model mechanism for MSUM induced membranolysis as follows. Binding of crystals to membranes induces the redistribution of transmembrane proteins into clusters or aggregates leading to pore formation. The pores permit the leakage of low molecular weight soluble compounds and ions across the membrane which is followed by osmotic rupture of the membran

The optical conductivity of graphene in the visible region of the spectrum

We compute the optical conductivity of graphene beyond the usual Dirac cone approximation, giving results that are valid in the visible region of the conductivity spectrum. The effect of next nearest neighbor hoping is also discussed. Using the full expression for the optical conductivity, the transmission and reflection coefficients are given. We find that even in the optical regime the corrections to the Dirac cone approximation are surprisingly small (a few percent). Our results help in the interpretation of the experimental results reported by Nair {\it et al.} [Science {\bf 320}, 1308 (2008)].Comment: 8 pages, 6 figure

Acute effects of elevated NEFA on vascular function: a comparison of SFA and MUFA

There is emerging evidence to show that high levels of NEFA contribute to endothelial dysfunction and impaired insulin sensitivity. However, the impact of NEFA composition remains unclear. A total of ten healthy men consumed test drinks containing 50 g of palm stearin (rich in SFA) or high-oleic sunflower oil (rich in MUFA) on separate occasions; a third day included no fat as a control. The fats were emulsified into chocolate drinks and given as a bolus (approximately 10 g fat) at baseline followed by smaller amounts (approximately 3 g fat) every 30 min throughout the 6 h study day. An intravenous heparin infusion was initiated 2 h after the bolus, which resulted in a three- to fourfold increase in circulating NEFA level from baseline. Mean arterial stiffness as measured by digital volume pulse was higher during the consumption of SFA (P,0·001) but not MUFA (P¼0·089) compared with the control. Overall insulin and gastric inhibitory peptide response was greater during the consumption of both fats compared with the control (P,0·001); there was a second insulin peak in response to MUFA unlike SFA. Consumption of SFA resulted in higher levels of soluble intercellular adhesion molecule-1 (sI-CAM) at 330 min than that of MUFA or control (P#0·048). There was no effect of the test drinks on glucose, total nitrite, plasminogen activator inhibitor-1 or endothelin-1 concentrations. The present study indicates a potential negative impact of elevated NEFA derived from the consumption of SFA on arterial stiffness and sI-CAM levels. More studies are needed to fully investigate the impact of NEFA composition on risk factors for CVD

Unintended and accidental medical radiation exposures in radiology: guidelines on investigation and prevention

This paper sets out guidelines for managing radiation exposure incidents involving patients in diagnostic and interventional radiology. The work is based on collation of experiences from representatives of international and national organizations for radiologists, medical physicists, radiographers, regulators, and equipment manufacturers, derived from an International Atomic Energy Agency Technical Meeting. More serious overexposures can result in skin doses high enough to produce tissue reactions, in interventional procedures and computed tomography, most notably from perfusion studies. A major factor involved has been deficiencies in training of staff in operation of equipment and optimization techniques. The use of checklists and time outs before procedures commence, and dose alerts when critical levels are reached during procedures can provide safeguards to reduce risks of these effects occurring. However, unintended and accidental overexposures resulting in relatively small additional doses can take place in any diagnostic or interventional X-ray procedure and it is important to learn from errors that occur, as these may lead to increased risks of stochastic effects. Such events may involve the wrong examinations, procedural errors, or equipment faults. Guidance is given on prevention, investigation and dose calculation for radiology exposure incidents within healthcare facilities. Responsibilities should be clearly set out in formal policies, and procedures should be in place to ensure that root causes are identified and deficiencies addressed. When an overexposure of a patient or an unintended exposure of a foetus occurs, the foetal, organ, skin and/or effective dose may be estimated from exposure data. When doses are very low, generic values for the examination may be sufficient, but a full assessment of doses to all exposed organs and tissues may sometimes be required. The use of general terminology to describe risks from stochastic effects is recommended rather than calculation of numerical values, as these are misleading when applied to individuals

Cooling of cryogenic electron bilayers via the Coulomb interaction

Heat dissipation in current-carrying cryogenic nanostructures is problematic because the phonon density of states decreases strongly as energy decreases. We show that the Coulomb interaction can prove a valuable resource for carrier cooling via coupling to a nearby, cold electron reservoir. Specifically, we consider the geometry of an electron bilayer in a silicon-based heterostructure, and analyze the power transfer. We show that across a range of temperatures, separations, and sheet densities, the electron-electron interaction dominates the phonon heat-dissipation modes as the main cooling mechanism. Coulomb cooling is most effective at low densities, when phonon cooling is least effective in silicon, making it especially relevant for experiments attempting to perform coherent manipulations of single spins.Comment: 9 pages, 5 figure

Kramers-Kronig, Bode, and the meaning of zero

The implications of causality, as captured by the Kramers-Kronig relations between the real and imaginary parts of a linear response function, are familiar parts of the physics curriculum. In 1937, Bode derived a similar relation between the magnitude (response gain) and phase. Although the Kramers-Kronig relations are an equality, Bode's relation is effectively an inequality. This perhaps-surprising difference is explained using elementary examples and ultimately traces back to delays in the flow of information within the system formed by the physical object and measurement apparatus.Comment: 8 pages; American Journal of Physics, to appea