Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis

BACKGROUND: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. METHODS: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. RESULTS: Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. CONCLUSIONS: Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease expression in arthritis-resistant mice provides support for the idea that periodontal infection may be able to trigger autoimmunity if other disease-eliciting factors are already present

Spin-Polaronic Effects in Electric Shuttling in a Single Molecule Transistor with Magnetic Leads

Current-voltage characteristics of a spintromechanical device, in which spin-polarized electrons tunnel between magnetic leads with anti-parallel magnetization through a single level movable quantum dot, are calculated. New exchange- and electromechanical coupling-induced (spin-polaronic) effects that determine strongly nonlinear current-voltage characteristics were found. In the low-voltage regime of electron transport the voltage-dependent and exchange field-induced displacement of quantum dot towards the source electrode leads to nonmonotonic behavior of differential conductance that demonstrates the lifting of spin-polaronic effects by electric field. At high voltages the onset of electron shuttling results in the drop of current and negative differential conductance, caused by mechanically-induced increase of tunnel resistivities and exchange field-induced suppression of spin-flips in magnetic field. The dependence of these predicted spin effects on the oscillations frequency of the dot and the strength of electron-electron correlations is discussed.Comment: 8 pages, 4 figure

Coulomb-promoted spintromechanics in magnetic shuttle devices

Exchange forces on the movable dot ("shuttle") in a magnetic shuttle device depend on the parity of the number of shuttling electrons. The performance of such a device can therefore be tuned by changing the strength $U$ of Coulomb correlations to block or unblock parity fluctuations. We show that by increasing $U$ the spintro-mechanics of the device crosses over, at $U=U_c(T)$, from a mechanically stable regime to a regime of spin-induced shuttle instabilities. This is due to enhanced spin-dependent mechanical forces as parity fluctuations are reduced by a Coulomb blockade of tunneling and demonstrates that single-electron manipulation of single-spin controlled nano-mechanics is possible.Comment: 5 pages, 2 figures and a supplementary information fil

Glaciers and small ice caps in the macro-scale hydrological cycle: an assessment of present conditions and future changes

Glacier and small ice cap melt water contributions to the global hydrologic cycle are an important component of human water supply and for sea level rise. This melt water is used in many arid and semi-arid parts of the world for direct human consumption as well as indirect consumption by irrigation for crops, serving as frozen reservoirs of water that supplement runoff during warm and dry periods of summer when it is needed the most. Additionally, this melt water reaching the oceans represents a direct input to sea level rise and therefore accurate estimates of this contribution have profound economic and geopolitical implications. It has been demonstrated that, on the scale of glacierized river catchments, land surface hydrological models can successfully simulate glacier contribution to streamflow. However, at global scales, the implementation of glacier melt in hydrological models has been rudimentary or non-existent. In this study, a global glacier mass balance model is coupled with the University of New Hampshire Water Balance/Transport Model (WBM) to assess recent and projected future glacier contributions to the hydrological cycle over the global land surface (excluding the ice sheets of Greenland and Antarctica). For instance, results of WBM simulations indicate that seasonal glacier melt water in many arid climate watersheds comprises 40 % or more of their discharge. Implicitly coupled glacier and WBM models compute monthly glacier mass changes and resulting runoff at the glacier terminus for each individual glacier from the globally complete Randolph Glacier Inventory including over 200 000 glaciers. The time series of glacier runoff is aggregated over each hydrological modeling unit and delivered to the hydrological model for routing downstream and mixing with non-glacial contribution of runoff to each drainage basin outlet. WBM tracks and uses glacial and non-glacial components of the in-stream water for filling reservoirs, transfers of water between drainage basins (inter-basin hydrological transfers), and irrigation along the global system of rivers with net discharge to the ocean. Climate scenarios from global climate models prepared for IPCC AR5 are used to explore an expected range of possible future glacier outflow variability to estimate the impacts on human use of these valuable waters and their poorly understood net contribution to sea level change

Mid-infrared optical parametric amplifier using silicon nanophotonic waveguides

All-optical signal processing is envisioned as an approach to dramatically decrease power consumption and speed up performance of next-generation optical telecommunications networks. Nonlinear optical effects, such as four-wave mixing (FWM) and parametric gain, have long been explored to realize all-optical functions in glass fibers. An alternative approach is to employ nanoscale engineering of silicon waveguides to enhance the optical nonlinearities by up to five orders of magnitude, enabling integrated chip-scale all-optical signal processing. Previously, strong two-photon absorption (TPA) of the telecom-band pump has been a fundamental and unavoidable obstacle, limiting parametric gain to values on the order of a few dB. Here we demonstrate a silicon nanophotonic optical parametric amplifier exhibiting gain as large as 25.4 dB, by operating the pump in the mid-IR near one-half the band-gap energy (E~0.55eV, lambda~2200nm), at which parasitic TPA-related absorption vanishes. This gain is high enough to compensate all insertion losses, resulting in 13 dB net off-chip amplification. Furthermore, dispersion engineering dramatically increases the gain bandwidth to more than 220 nm, all realized using an ultra-compact 4 mm silicon chip. Beyond its significant relevance to all-optical signal processing, the broadband parametric gain also facilitates the simultaneous generation of multiple on-chip mid-IR sources through cascaded FWM, covering a 500 nm spectral range. Together, these results provide a foundation for the construction of silicon-based room-temperature mid-IR light sources including tunable chip-scale parametric oscillators, optical frequency combs, and supercontinuum generators

Heisenberg's Uncertainty Relation and Bell Inequalities in High Energy Physics

An effective formalism is developed to handle decaying two-state systems. Herewith, observables of such systems can be described by a single operator in the Heisenberg picture. This allows for using the usual framework in quantum information theory and, hence, to enlighten the quantum feature of such systems compared to non-decaying systems. We apply it to systems in high energy physics, i.e. to oscillating meson-antimeson systems. In particular, we discuss the entropic Heisenberg uncertainty relation for observables measured at different times at accelerator facilities including the effect of CP violation, i.e. the imbalance of matter and antimatter. An operator-form of Bell inequalities for systems in high energy physics is presented, i.e. a Bell-witness operator, which allows for simple analysis of unstable systems.Comment: 17 page

Gated Diffusion-controlled Reactions

The binding and active sites of proteins are often dynamically occluded by motion of the nearby polypeptide. A variety of theoretical and computational methods have been developed to predict rates of ligand binding and reactivity in such cases. Two general approaches exist, "protein centric" approaches that explicitly treat only the protein target, and more detailed dynamical simulation approaches in which target and ligand are both treated explicitly. This mini-review describes recent work in this area and some of the biological implications