• Peripheral B-cell tolerance is defective in IPEX patients, suggesting that Tregs are involved in the maintenance of B-cell tolerance.• T cells, including Tregs, display an activated phenotype in IPEX patients that may favor the accumulation of autoreactive B cells. Regulatory T cells (Tregs IntroductionImmune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a primary immunodeficiency with severe autoimmunity caused by mutations in the forkhead box protein 3 (FOXP3) gene. 1,2 A similar phenotype is observed in scurfy mice that carry a mutation in their foxp3 gene. FOXP3 encodes a transcription factor essential for the function of natural thymusderived CD4 ϩ CD25 ϩ FOXP3 ϩ regulatory T cells (Tregs), which in turn are critically important in maintaining self-tolerance in both mice and humans. [3][4][5] Multiple and diverse autoantibodies are commonly identified in the sera of IPEX patients, suggesting that Tregs may represent a key regulator for autoreactive B cells. 6 Antibodies are generated during early B-cell development by random joining of immunoglobulin (Ig) gene segments and therefore can result in the assembly of autoreactive antibodies or B-cell receptors (BCRs). It has been previously demonstrated that most developing autoreactive B cells in humans are removed at 2 discrete steps. 7 First, a central checkpoint in the bone marrow between early immature and immature B cells removes the majority of developing B cells that express highly polyreactive antibodies and only a small fraction of clones with low levels of polyreactivity migrate to the periphery. Then, a peripheral B-cell tolerance checkpoint further counterselects autoreactive new emigrant B cells before they enter the mature naive B-cell compartment. 7 The regulation of central B-cell tolerance in humans seems to be mostly controlled by B cell-intrinsic factors, which potentially include self-antigen binding receptors such as BCRs and Toll-like receptors (TLRs). [8][9][10][11] Relatively less is known about the mechanisms that control the peripheral B-cell tolerance checkpoint in humans. The analysis of CD40L-and MHC class II-defective patients demonstrated that while developing autoreactive B cells are properly counterselected in the bone marrow in these patients, their mature naive B cells express a high proportion of autoreactive antibodies, including antinuclear antibodies (ANAs). 12 These findings strongly supported the idea that a CD4 ϩ T-cell population requiring CD40L and potentially self-antigen presentation through MHC class II likely prevent the accumulation of autoreactive B cells in Submitted September 20, 2012; accepted November 14, 2012. Prepublished online as Blood First Edition paper, December 5, 2012; DOI 10.1182 DOI 10. /blood-2012 The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC sectio...

We demonstrate a dual wavelength acousto-optic deflector (AOD) designed to deflect two wavelengths to the same angles by driving with two RF frequencies. The AOD is designed as a beam scanner to address two-photon transitions in a two-dimensional array of trapped neutral Rb87 atoms in a quantum computer. Momentum space is used to design AODs that have the same diffraction angles for two wavelengths (780 and 480 nm) and have nonoverlapping Bragg-matched frequency response at these wavelengths, so that there will be no cross talk when proportional frequencies are applied to diffract the two wavelengths. The appropriate crystal orientation, crystal shape, transducer size, and transducer height are determined for an AOD made with a tellurium dioxide crystal (TeO(2)). The designed and fabricated AOD has more than 100 resolvable spots, widely separated band shapes for the two wavelengths within an overall octave bandwidth, spatially overlapping diffraction angles for both wavelengths (780 and 480 nm), and a 4 micros or less access time. Cascaded AODs in which the first device upshifts and the second downshifts allow Doppler-free scanning as required for addressing the narrow atomic resonance without detuning. We experimentally show the diffraction-limited Doppler-free scanning performance and spatial resolution of the designed AOD.

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We present an optimized design of an acousto-optic tunable filter (AOTF) using a phased-array transducer for a spectrally-multiplexed ultrafast pulse-shaping RF beamformer application. The momentum-space interaction geometry is used to optimize an AOTF using acoustic beam-steering techniques in combination with acoustic anisotropy in order to linearly map the applied RF frequency to the filtered output optical frequency. The appropriate crystal orientation and phased-array transducer design are determined to linearize the RF to optical frequency mapping even in the presence of optical dispersion of the birefringence. After optimizing the phasedarray transducer, acoustic anisotropy, and optical anisotropic diffraction geometry, the designed AOTF will compensate for the birefringent dispersion of TeO 2 to give a linear modulation of RF frequencies onto the corresponding optical frequencies. This linearized frequency mapped AOTF is required for a squint-compensated, wavelength-multiplexed, optically processed RF imager.

We investigated the dependence of image quality on the temperature of a position sensitive avalanche photodiode (PSAPD)-based small animal single photon emission computed tomography (SPECT) gamma camera with a CsI:Tl scintillator. Currently, nitrogen gas cooling is preferred to operate PSAPDs in order to minimize the dark current shot noise. Being able to operate a PSAPD at a relatively high temperature (e.g., 5 °C) would allow a more compact and simple cooling system for the PSAPD. In our investigation, the temperature of the PSAPD was controlled by varying the flow of cold nitrogen gas through the PSAPD module and varied from −40 °C to 20 °C. Three experiments were performed to demonstrate the performance variation over this temperature range. The point spread function (PSF) of the gamma camera was measured at various temperatures, showing variation of full-width-half-maximum (FWHM) of the PSF. In addition, a 99mTc-pertechnetate (140 keV) flood source was imaged and the visibility of the scintillator segmentation (16×16 array, 8 mm × 8 mm area, 400 μm pixel size) at different temperatures was evaluated. Comparison of image quality was made at −25 °C and 5 °C using a mouse heart phantom filled with an aqueous solution of 99mTc-pertechnetate and imaged using a 0.5 mm pinhole collimator made of tungsten. The reconstructed image quality of the mouse heart phantom at 5 °C degraded in comparision to the reconstructed image quality at −25 °C. However, the defect and structure of the mouse heart phantom were clearly observed, showing the feasibility of operating PSAPDs for SPECT imaging at 5 °C, a temperature that would not need the nitrogen cooling. All PSAPD evaluations were conducted with an applied bias voltage that allowed the highest gain at a given temperature.