Activation/inactivation of CD4+ T cells in context of the Quorum Hypothesis

Understanding how immunological tolerance is established has been the subject of intense investigation and several models have been put forward to define the circumstances under which antigens activate or inactivate lymphocytes. According to the commonly held Danger Model, a single CD4+ T cell can be activated by an antigen presenting cell (APC) under appropriately "dangerous" conditions that instruct the APC to upregulate its expression of co-stimulatory molecules necessary for CD4+ T cell activation. In the absence of danger signals, CD4+ T cell inactivation ensues. Conversely, the Quorum Hypothesis postulates that the antigen-dependent, B cell-mediated cooperation between a minimum number of antigen-specific CD4+ T cells leads to their activation, whereas too few antigen-specific CD4+ T cells would be inactivated by antigen. Using enzyme-linked immunospot assay and flow cytometry, we investigated whether the activation of murine T cell receptor transgenic CD4+ T cells in vitro was quorum-dependent. The number of cultured CD4+ T cells was critical to their ability to generate IL-2 and/or interferon gamma (IFN-) producing cells. In general, relatively low numbers of CD4+ T cells did not generate cytokine-producing cells, medium numbers generated IL-2-producing cells, while higher numbers generated IL-2 and IFN--producing cells. This quorum effect in the generation of cytokine-producing cells was not mediated by a difference in the proliferation of CD4+ T cells cultured under different conditions. Importantly, CD4+ T cells generated cytokine-producing cells without the deliberate use of Danger molecules, leading to the suggestion that Danger signals were not critical for CD4+ T cell activation. Moreover, our observations suggest that quorum sensing is mediated by a linked mechanism. CD4+ T cells specific for a non-crossreacting antigen optimally facilitated the activation of CD4+ T cells specific for the target antigen only if the two antigens were presented by the same APC. Lastly, our preliminary observations support a difference in the role of dendritic cells and B cells in mediating quorum sensing. In conclusion, our observations are consistent with the predictions of the Quorum Hypothesis. Further investigation is required to determine if CD4+ T cells are inactivated by antigen if cultured at limiting densities

Experimental Verification of Electromagnetic Simulations of a HIFI Mixer Sub-Assembly

Phase II of the study "Far-Infrared Optics Design & Verification", commissioned by the European Space Agency (ESA), we investigate the ability of several commercial software packages (GRASP, CODEV, GLAD and ASAP) to predict the performance of a representative example of a submillimeter-wave optical system. In this paper, we use the software packages to predict the behaviour of a Mixer Sub-Assembly (MSA) of HIFI, and we compare the simulations with near-field measurements at 480 GHz. In order to be able to distinguish between the predictions of the packages, we move the corrugated horn of the MSA through its nominal focus position. A unique feature of the experimental arrangement is that the measured position of every field point is known absolutely to within fractions of a wavelength. In this paper we present the results of this through-focus experiment, which give a good first-order indication of the agreement between measured and simulated behaviour of a typical submillimeter-wave optical system

The Influence of LO Power Heating of the Tunnel Junction on the Performance of THz SIS Mixers

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Prototype finline-coupled TES bolometers for CLOVER

CLOVER is an experiment which aims to detect the signature of gravitational waves from inflation by measuring the B-mode polarization of the cosmic microwave background. CLOVER consists of three telescopes operating at 97, 150, and 220 GHz. The 97-GHz telescope has 160 feedhorns in its focal plane while the 150 and 220-GHz telescopes have 256 horns each. The horns are arranged in a hexagonal array and feed a polarimeter which uses finline-coupled TES bolometers as detectors. To detect the two polarizations the 97-GHz telescope has 320 detectors while the 150 and 220-GHz telescopes have 512 detectors each. To achieve the target NEPs (1.5, 2.5, and 4.5x10^-17 W/rtHz) the detectors are cooled to 100 mK for the 97 and 150-GHz polarimeters and 230 mK for the 220-GHz polarimeter. Each detector is fabricated as a single chip to ensure a 100% operational focal plane. The detectors are contained in linear modules made of copper which form split-block waveguides. The detector modules contain 16 or 20 detectors each for compatibility with the hexagonal arrays of horns in the telescopes' focal planes. Each detector module contains a time-division SQUID multiplexer to read out the detectors. Further amplification of the multiplexed signals is provided by SQUID series arrays. The first prototype detectors for CLOVER operate with a bath temperature of 230 mK and are used to validate the detector design as well as the polarimeter technology. We describe the design of the CLOVER detectors, detector blocks, and readout, and present preliminary measurements of the prototype detectors performance.Comment: 4 pages, 6 figures; to appear in the Proceedings of the 17th International Symposium on Space Terahertz Technology, held 10-12 May 2006 in Pari

Globalization, democratization, and the Arab uprising : the international factor in MENA's failed democratization

What explains the almost negative impact of international factors on post-Uprising democratization prospects? This article compares the utility of rival “diffusionist” and neo-Gramscian political economy frames to explain this. Three international factors deter democratization. The failure of Western democracy promotion is rooted in the contradiction between the dominance of global finance capital and the norm of democratic equality; in the periphery, neo-liberalism is most compatible with hybrid regimes and, at best, “low intensity democracy.” In MENA, neo-liberalism generated a crony capitalism incompatible with democratization; while this also sparked the uprisings, these have failed to address class inequalities. Moreover at the normative level, MENA hosts the most credible counter-hegemonic ideologies; the brief peaking of democratic ideology in the region during the early uprisings soon declined amidst regional discourse wars. Non-democrats—coercive regime remnants and radical charismatic movements--were empowered by the competitive interference of rival powers in Uprising states. The collapse of many Uprising states amidst a struggle for power over the region left an environment uncongenial to democratization.PostprintPeer reviewe

A millimeter unilateral finline SIS mixer with a wide IF bandwidth

Superconductor-Insulator-Superconductor (SIS) tunnel junction mixers are now commonly used in as- tronomical receivers at (sub)millimeter wavelengths because of their superb sensitivity, high dynamic range and stability of operation. Niobium SIS mixers operating at frequencies well below the super- conducting gap (∼680 GHz) have already achieved quantum limited sensitivity. Therefore to further enhance the receiver sensitivity, increasing the Intermediate Frequency (IF) bandwidth of SIS mixers has became crucial. This thesis focuses on the theoretical modeling, design and experimental verifi- cation of Nb SIS mixers operating around 230 GHz with a wide IF bandwidth of 1–15 GHz. These mixers were designed for a single baseline heterodyne interferometer (GUBBINS), which is being built to observe the Sunyaev-Zel’dovich effect in the Cosmic Microwave Background. The combination of wide IF bandwidth SIS mixers and complex analogue correlators will allow GUBBINS to feature high surface brightness sensitivity, that helps to distinguish the weak SZ effect from the background noise. The SIS mixer detector system was assembled inside the GUBBINS cryostat together with the IF electronics and RF/LO optical systems. Low noise temperatures of around 71 K were then measured in the GUBBINS system. The Nb SIS mixer we have developed uses a unilateral finline and fully integrated planar circuits deposited on a silicon substrate, to couple the electromagnetic radiation from the waveguide into the SIS junction. The finline mixer allows a broad-band RF coupling, an easy integration of the on-chip planar circuits and an easy-to-fabricate mixer block. To achieve a wide IF bandwidth, the output impedance of the SIS mixer was well matched to the input impedance of the amplifier by a multi-stage microstrip circuit. Additionally, the planar circuit of the SIS mixer was also designed to have a small lumped inductance and capacitance. The SIS mixer chip was extensively simulated by rigorous electromagnetic software (HFSS) and the S-parameter was exported to a quantum mixing package SuperMix to produce a full-wave model of the mixer. Experimental testing yielded a best noise temperature of 50 K with an average noise temperature of 75 K over an RF bandwidth of 160 GHz– 260 GHz. We have performed thorough experimental and computational investigation of the IF system in particular the constraints on the bandwidth caused by the lumped element capacitance of the mixer chip and the matching of the output impedance of the mixer to the IF amplifier. Our conclusion is that a bandwidth of 1–15 GHz could be achieved using our mixer design, subject to the performance of the amplifier. Finally, a variable temperature load system was successfully developed and tested inside the cryostat, to avoid the losses from the room-temperature optics. We have showed that the noise temperature of the SIS detector could be reduced by as much as 15 K by testing the mixer using a variable temperature load inside the cryostat.This thesis is not currently available in ORA

Development of superconducting bolometer device technology for millimeter-wave cosmology instruments

The Cold-Electron Bolometer (CEB) is a sensitive detector of millimeter-wave radiation, in which tunnel junctions are used as temperature sensors of a nanoscale normal metal strip absorber. The absorber is fed by an antenna via two Superconductor-Insulator-Normal metal (SIN) tunnel junctions, fabricated at both ends of the absorber. Incoming photons excite electrons, heating the whole electron system. The incoming RF power is determined by measuring the tunneling current through the SIN junctions. Since electrons at highest energy levels escape the absorber through the tunnel junctions, it causes cooling of the absorber. This electron cooling provides electro-thermal feedback that makes the saturation power of a CEB well above that of other types of millimeter-wave receivers. The key features of CEB detectors are high sensitivity, large dynamic range, fast response, easy integration in arrays on planar substrates, and simple readout. The high dynamic range allows the detector to operate under relatively high background levels. In this thesis, we present the development and successful operation of CEB, focusing on the fabrication technology and different implementations of the CEB for efficient detection of electromagnetic signals. We present the CEB detector integrated across a unilateral finline deposited on a planar substrate. We have measured the finline-integrated CEB performance at 280-315 mK using a calibrated black-body source mounted inside the cryostat. The results have demonstrated strong response to the incoming RF power and reasonable sensitivity. We also present CEB devices fabricated with advanced technologies and integrated in log-periodic, double-dipole and cross-slot antennas. The measured CEB performance satisfied the requirements of the balloon-borne experiment BOOMERANG and could be considered for future balloon-borne and ground-based instruments. In this thesis we also investigated a planar phase switch integrated in a back-to-back finline for modulating the polarization of weak electromagnetic signals. We examine the switching characteristics and demonstrate that the switching speed of the device is well above the speed required for phase modulation in astronomical instruments. We also investigated the combination of a detector and a superconducting phase switch for modulating the polarization of electromagnetic radiation.This thesis is not currently available in ORA