Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo

Abstract The transcription factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pathway, which is a critical regulator of T cell development in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells. We further show that resting T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation.</jats:p

Thermo-mechanical sensitivity calibration of nanotorsional magnetometers

We report on the fabrication of sensitive nanotorsional resonators, which can be utilized as magnetometers for investigating the magnetization dynamics in small magnetic elements. The thermo-mechanical noise is calibrated with the resonator displacement in order to determine the ultimate mechanical torque sensitivity of the magnetometer.Comment: 56th Annual Conference on Magnetism and Magnetic Material

Declining discount rates

We ask whether the US government should replace its current discounting practices with a declining discount rate schedule, as the United Kingdom and France have done, or continue to discount the future at a constant exponential rate. We present the theoretical basis for a declining discount rate (DDR) schedule, but focus on how, in practice, a DDR could be estimated for use by policy analysts. We discuss the empirical approaches in the literature and review how the United Kingdom and France estimated their DDR schedules. We conclude with advice on how the United States might proceed to consider modifying its current discounting practices

Dissipative and Dispersive Optomechanics in a Nanocavity Torque Sensor

Dissipative and dispersive optomechanical couplings are experimentally observed in a photonic crystal split-beam nanocavity optimized for detecting nanoscale sources of torque. Dissipative coupling of up to approximately $500$ MHz/nm and dispersive coupling of $2$ GHz/nm enable measurements of sub-pg torsional and cantilever-like mechanical resonances with a thermally-limited torque detection sensitivity of 1.2$\times 10^{-20} \text{N} \, \text{m}/\sqrt{\text{Hz}}$ in ambient conditions and 1.3$\times 10^{-21} \text{N} \, \text{m}/\sqrt{\text{Hz}}$ in low vacuum. Interference between optomechanical coupling mechanisms is observed to enhance detection sensitivity and generate a mechanical-mode-dependent optomechanical wavelength response.Comment: 11 pages, 6 figure

The Role of Encoding Strategy in Younger and Older Adult Associative Recognition: A Think-Aloud Analysis

Older adults have especially poor recognition memory for word pairs, and recent research suggests this associative deficit manifests primarily in older adults’ higher rates of false alarms compared to younger adults. This could result from older adults either failing to generate meaningful (deep) mediators at study, or failing to benefit from having generated deep mediators at test. Younger and older adults performed a recognition memory task for words and word-pairs. A think-aloud analysis of their spontaneous encoding strategies (e.g., repetition, shallow mediators, and deep mediators) revealed that generation of deep mediators did not differ between younger and older adults, and was associated with high hit rates for items and associates in both age groups. However, generation of deep mediators was inversely related to false alarm rates in younger adults but not older adults. A trial-level analysis of encoding strategies and recognition responses revealed that younger adults benefited from having generated deep mediators when presented with corresponding recombined pairs at test as shown in their lower false alarm rates. In contrast, older adults who generated deep mediators during study (e.g., to blanket-figure) did not benefit from having done so when they encountered the corresponding recombined pairs at test (blanket-summer and district-figure): Their false alarm rates to pairs at test were unrelated to generation of deep mediators at study. These results suggest that many older adults have difficulty retrieving their mediators when presented with recombined pairs at test, older adults’ mediators are not distinct enough to individuate intact pairs from recombined pairs at test, or some combination of both

Pension plan solvency and extreme market movements : a regime switching approach

We develop and test a new approach to assess defined benefit pension plan solvency risk in the presence of extreme market movements. Our method captures both the ‘fat-tailed’ nature of asset returns and their correlation with discount rate changes. We show that the standard assumption of constant discount rates leads to dramatic underestimation of future projections of pension plan solvency risk. Failing to incorporate leptokurtosis into asset returns also leads to downward biased estimates of risk, but this is less pronounced than the time-varying discount rate e§ect. Further modifying the model to capture the correlation between asset returns and the discount rate provides additional improvements in the projection of future pension plan solvency. This reduces the perceived future risk of underfunding because of the negative correlation between interest rate changes and asset returns. These results have important implications for those with responsibility for balancing risk against expected return when seeking to improve the current poor funding positions of defined benefit pension schemes

From filters to features:Scale-space analysis of edge and blur coding in human vision

To make vision possible, the visual nervous system must represent the most informative features in the light pattern captured by the eye. Here we use Gaussian scale-space theory to derive a multiscale model for edge analysis and we test it in perceptual experiments. At all scales there are two stages of spatial filtering. An odd-symmetric, Gaussian first derivative filter provides the input to a Gaussian second derivative filter. Crucially, the output at each stage is half-wave rectified before feeding forward to the next. This creates nonlinear channels selectively responsive to one edge polarity while suppressing spurious or "phantom" edges. The two stages have properties analogous to simple and complex cells in the visual cortex. Edges are found as peaks in a scale-space response map that is the output of the second stage. The position and scale of the peak response identify the location and blur of the edge. The model predicts remarkably accurately our results on human perception of edge location and blur for a wide range of luminance profiles, including the surprising finding that blurred edges look sharper when their length is made shorter. The model enhances our understanding of early vision by integrating computational, physiological, and psychophysical approaches. © ARVO

Preliminary Investigation of Novel Bone Graft Substitutes based on Strontium-Calcium-Zinc-Silicate Glasses

Bone graft procedures typically require surgeons to harvest bone from a second site on a given patient (Autograft) before repairing a bone defect. However, this results in increased surgical time, excessive blood loss and a significant increase in pain. In this context a synthetic bone graft with excellent histocompatibility, built in antibacterial efficacy and the ability to regenerate healthy tissue in place of diseased tissue would be a significant step forward relative to current state of the art philosophies. We developed a range of calcium-strontium-zinc-silicate glass-based bone grafts and characterized their structure and physical properties, then evaluated their in vitro cytotoxicity and in vivo biocompatibility using standardized models from the literature. A graft (designated BT109) of composition 0.28SrO/0.32ZnO/0.40 SiO2 (mol fraction) was the best performing formulation in vitro shown to induce extremely mild cytopathic effects (cell viability up to 95%) in comparison with the commercially available bone graft Novabone® (cell viability of up to 72%). Supplementary to this, the grafts were examined using the standard rat femur healing model on healthy Wister rats. All grafts were shown to be equally well tolerated in bone tissue and new bone was seen in close apposition to implanted particles with no evidence of an inflammatory response within bone. Complimentary to this BT109 was implanted into the femurs of ovariectomized rats to monitor the response of osteoporotic tissue to the bone grafts. The results from this experiment indicate that the novel grafts perform equally well in osteoporotic tissue as in healthy tissue, which is encouraging given that bone response to implants is usually diminished in ovariectomized rats. In conclusion these materials exhibit significant potential as synthetic bone grafts to warrant further investigation and optimisation. © 2008 Springer Science+Business Media, LLC