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We propose a treatment of HIV‐1+ individuals designed to harness protective immunity, lead to viral containment, and so render the individual minimally infectious. A few HIV‐infected individuals, 'elite controllers', generate a stable Th1, cytotoxic T lymphocyte response that contains the virus. Most infected individuals, in the absence of therapy, first generate a similarly protective response that evolves with time a Th2 component, associated with antibody production and loss of viral control. Cessation of anti‐retroviral treatment after three years results in viral rebound in most, but about one in seven individuals contains the virus, so‐called post‐treatment controllers. We suggest an understanding, of how the Th1/Th2 phenotype of immune responses is controlled, can explain these different outcomes and leads us to propose a non‐invasive, personalized strategy of immunotherapy. We propose that monitoring the relative prevalence of HIV‐1 specific IgG1 and IgG2 antibodies can provide a biomarker for deciding when to interrupt/withdraw anti‐retroviral therapy to optimally harness protective immunity. [ABSTRACT FROM AUTHOR]

We propose a framework to explain how T cells achieve specificity and sensitivity, how the affinity of the TcR peptide/MHC interaction controls positive and negative thymic selection and mature T cell survival, and whether antigen‐dependent activation and inactivation takes place. Two distinct types of signalling can lead to mature T cell multiplication. One requires the TcR to recognize with a certain affinity an antigen‐derived peptide, an agonist peptide, bound to an MHC molecule. The other, the tonic signal, leads to naïve T cell survival and modest proliferation if the T cell successfully competes for endogenous, self‐peptide/MHC ligands, involving lower affinity TCR/ligand interactions. Many suggest lymphopenia contributes to autoimmunity by increasing the strength of TcR‐tonic signalling, and so activation of anti‐self T cells. We suggest T cell activation requires antigen‐mediated cooperation between T cells. Increased tonic signalling under lymphopenic conditions facilitates T cell proliferation and so antigen‐dependent cooperation and activation of anti‐self T cells. [ABSTRACT FROM AUTHOR]

Recent reports suggest a quorum of T cells is required to activate T lymphocytes and that this requirement may help explain why scarce lymphocytes, specific for peripheral self-antigen, are rarely activated by Ag. This proposal runs counter to the commonly held framework that the Ag-dependent, but CD4 T lymphocyte-independent, activation of CD8 T lymphocytes, and the activation of CD4 T lymphocytes themselves, can occur when a single CD8 or CD4 T lymphocyte encounters Ag under appropriately dangerous circumstances. We argue that a review of older literature often ignored, as well as of contemporary studies, supports the quorum concept and is difficult to reconcile with the Danger Model. [ABSTRACT FROM AUTHOR]

Abstract: We present the design of a low loss planar phase switch operating at millimetre and submillimetre wavelengths. The system comprises a superconducting nanostrip that switches the RF signal between the two branches of a microstrip phase circuit. The employment of superconducting components reduces conduction losses to a negligible level. The required cooling below the transition temperature does not add extra effort since all high performance detectors employ superconducting circuits, and are in fact cooled well below the transition temperature of the phase circuit material. The proposed fully planar design allows the switch to be easily integrated into the detector circuit and eventually the realisation of a fully planar receiver. This avoids the use of bulky, expensive and lossy waveguide components and allows the fabrication of reliable and cheaply mass producible polarimeters that are now routinely used in large format CMB arrays. [Copyright &y& Elsevier]

Presents the design of a novel two-element horn-reflector antenna, which has been used on an interferometer built for studying the anistropy in the cosmic microwave background (CMB). Components of the CMB; Description of the design and fields of the antenna; Calculation of the antenna fields and radiation pattern; Design parameters for the antenna.

Presents a study which described a procedure for stimulating the behavior of partially coherent submillimeter-wave antenna systems. Statistical vector fields; Matrix representation of partially coherent systems; Analysis of a circular-waveguide bolometer.

Describes the design and operation of a finline superconductor-insulator-superconductor mixer. Use of a horn-reflector antenna to feed the mixer; Fabrication of the superconducting circuit using planar-circuit technology and fully integrated tuning.

Antigen‐specific molecules of the immune system, namely antibodies, the membrane immunoglobulins (mIgs) of B cells and T cell receptors (TcRs), can all signal their interaction with antigen. There are different mechanisms by which this signalling could occur. These mechanisms can be divided into two general categories: allosteric and non‐allosteric. In allosteric mechanisms, the monovalent binding of the antigen to the receptor triggers a conformational change at the binding site that is propagated to an invariant part of the receptor, a change recognized by a sensing unit. We argue allosteric mechanisms are implausible. Non‐allosteric mechanisms depend on steric effects due to the antigen's size and/or multivalency. We consider two non‐allosteric mechanisms by which the mIg of B cells has been envisaged to signal its interaction with antigen: the popular cross‐linking model and the dissociation activation model. We argue, on the basis of both experimental observations and physiological considerations, that the dissociation activation model, developed by Reth and his colleagues, is uniquely plausible. [ABSTRACT FROM AUTHOR]

Our previous in vivo studies show that both the amount of Ag and the number of available naive CD4 T cells affect the Th1/Th2 phenotype of the effector CD4 T cells generated. We examined how the number of OVA-specific CD4 TCR transgenic T cells affects the Th1/Th2 phenotype of anti-SRBC CD4 T cells generated in vivo upon immunization with different amounts of OVA-SRBC. Our observations show that a greater number of Ag-dependent CD4 T cell interactions are required to generate Th2 than Th1 cells. We established an in vitro system that recapitulates our main in vivo findings to more readily analyze the underlying mechanism. The in vitro generation of Th2 cells depends, as in vivo, upon both the number of responding CD4 T cells and the amount of Ag. We demonstrate, using agonostic/antagonistic Abs to various costimulatory molecules or their receptors, that the greater number of CD4 T cell interactions, required to generate Th2 over Th1 cells, does not involve CD40, OX40, or ICOS costimulation, but does involve B7/CD28 interactions. A comparison of the level of expression of B7 molecules by APC and CD4 T cells, under different conditions resulting in the substantial generation of Th1 and Th2 cells, leads us to propose that the critical CD28/B7 interactions, required to generate Th2 cells, may directly occur between CD4 T cells engaged with the same B cell acting as an APC. [ABSTRACT FROM AUTHOR]

We present a design of a high performance horn operating at 700 GHz. The feed, which comprises three smooth-walled conical sections, is easy to machine and yet has comparable performance to a corrugated horn. The measured radiation patterns show high main beam circularity, low sidelobe level and good agreement with theoretical predictions. The cross-polar level is below −20 dB across a frequency bandwidth of 140 GHz. The new design allows the fabrication of high performance, large format feed arrays cheaply and rapidly. [ABSTRACT FROM AUTHOR]

We present experimental results on the testing of cold-electron bolometer (CEB) detectors comprised of a thin Ti film absorber and two SIN junctions integrated with a planar antenna. The CEB performance was tested in a He³ sorption cryostat HELIOX-AC-V at bath temperatures of 280-305 mK. The optical response was measured using the hot/cold load method by flipping a Cu reflector opposite a blackbody surface inside a 3 K shield and using a thermal source with variable temperature. In the first experiment, the detector chip was mounted in an optical sample-holder whose aperture was switched towards or away from a blackbody source changing the incident radiation temperature from 3 K to 270 mK. As a result, we measured the optical response to a 3 K=270 mK radiation temperature change. The measured voltage response value for the detector integrated in a double-dipole antenna was δVout = 120 µV. This corresponds to a noise equivalent power of NEP = Vn=(dV=dP) = 3:5 × 10-17 W Hz-1/2, where dV=dP is the voltage to power response obtained from the incoming power estimation based on the Planck formula. [ABSTRACT FROM AUTHOR]