Helper T cells for cytotoxic T lymphocytes need not be I region restricted.

We investigated the antigenic requirements for restimulation of H-2- restricted cytolytic T lymphocytes (CTL) in vitro to determine whether H-2 I region-restricted helper T cells are required in these responses. In one set of experiments, we studied the in vitro response of (responder x nonresponder)F(1) female T cells to the male antigen H-Y. We chose to examine this response because it has been suggested that the defect in nonresponder strains is a failure of helper T cells to recognize H-Y in association with nonresponder I region determinants. However, we find that nonresponder male stimulator cells are as effective as F(1) male stimulator cells at inducing H-Y-specific CTL responses. This finding calls into question reports that secondary CTL responses to H-Y are dependent upon the activation of H-Y- specific helper T cells restricted to responder type I region determinants. In a second set of experiments, we examined the requirements for restimulation of H-2-restricted T cells specific for minor-histocompatibility antigens from long-term mixed lymphocyte cultures. These cultures were established by repeatedly restimulating cultures of specific T cells with H- 2-matched stimulator cells expressing foreign minor histocompatibility antigens. We found that H-2D-restricted T ceils, including CTL, could be restimulated with cells that were matched with the responding cells at only the D region genes. This response did not appear to result from positive allogeneic effects or from antigen processing and representation by responder type APC that might contaminate the cultures. Thus, we find no evidence for a requirement for I region-restricted helper T cells in these CTL responses. However, helper T cells are required because we find that CTL lines derived by limit-dilution cloning from these long-term MLC are absolutely dependent upon exogenous helper factors for growth. The most simple interpretation of these results is that the helper cells are restricted to H-2 antigens other than I region antigens or to antigens that code outside of the H-2 complex. Finally, we show that factor-dependent CTL lines must recognize their specific antigen to proliferate, even in the presence of exogenous factors. The requirement of activated CTL for antigen to proliferate provides an explanation for how specific CTL can be selectively enriched in MLC by specific antigen stimulation. Furthermore, it is at variance with reports that memory CTL or activated CTL require only interleukin 2 for restimulation

The next phase of healthcare improvement: what can we learn from social movements?

To date, improvement in health care has relied mainly on a "top down" programme by programme approach to service change and development. This has spawned a multitude of different and often impressive improvement schemes and activities. We question whether what has been happening will be sufficient to achieve the desired scale of change within the time scales set. Is it a case of "more of the same" or are there new and different approaches that might now be usefully implemented? Evidence from the social sciences suggests that other perspectives may help to recast large scale organisational change efforts in a new light and offer a different, though complementary, approach to improvement thinking and practice. Particularly prominent is the recognition that such large scale change in organisations relies not only on the "external drivers" but on the ability to connect with and mobilise people?s own "internal" energies and drivers for change, thus creating a "bottom up" locally led "grass roots" movement for improvement and change

Towards a million change agents. A review of the social movements literature: implications for large scale change in the NHS.

This review explores 'social movements' as a new way of thinking about large-scale systems change and assesses the potential contribution of applying this new perspective to NHS improvement

Real space first-principles derived semiempirical pseudopotentials applied to tunneling magnetoresistance

In this letter we present a real space density functional theory (DFT) localized basis set semi-empirical pseudopotential (SEP) approach. The method is applied to iron and magnesium oxide, where bulk SEP and local spin density approximation (LSDA) band structure calculations are shown to agree within approximately 0.1 eV. Subsequently we investigate the qualitative transferability of bulk derived SEPs to Fe/MgO/Fe tunnel junctions. We find that the SEP method is particularly well suited to address the tight binding transferability problem because the transferability error at the interface can be characterized not only in orbital space (via the interface local density of states) but also in real space (via the system potential). To achieve a quantitative parameterization, we introduce the notion of ghost semi-empirical pseudopotentials extracted from the first-principles calculated Fe/MgO bonding interface. Such interface corrections are shown to be particularly necessary for barrier widths in the range of 1 nm, where interface states on opposite sides of the barrier couple effectively and play a important role in the transmission characteristics. In general the results underscore the need for separate tight binding interface and bulk parameter sets when modeling conduction through thin heterojunctions on the nanoscale.Comment: Submitted to Journal of Applied Physic

Convergence of eigenfunction expansions corresponding to nonlinear Sturm-Liouville operators

It is well known that the classical linear Sturm-Liouville eigenvalue problem is self-adjoint and possesses a family of eigenfunctions which form an orthonormal basis for the space L. A natural question is to ask if a similar result holds for nonlinear problems. In the present paper, we examine the basis property for eigenfunctions of nonlinear Sturm-Liouville equations subject to general linear, separated boundary conditions

Digital Doppler extraction demonstration with the advanced receiver

A digital Doppler extraction demonstration with the Advanced Receiver 2 (ARX 2) tracking Pioneer 10 and Voyager 2 is described. The measured results are compared with those of the Block 4 receiver that was operating in parallel with the ARX 2. It is shown that the ARX 2 outperforms the Block 4 receiver in terms of Allan variance of the Doppler residuals, the amount of which depends on the scenario of interest

Trajectory generation for road vehicle obstacle avoidance using convex optimization

This paper presents a method for trajectory generation using convex optimization to find a feasible, obstacle-free path for a road vehicle. Consideration of vehicle rotation is shown to be necessary if the trajectory is to avoid obstacles specified in a fixed Earth axis system. The paper establishes that, despite the presence of significant non-linearities, it is possible to articulate the obstacle avoidance problem in a tractable convex form using multiple optimization passes. Finally, it is shown by simulation that an optimal trajectory that accounts for the vehicle’s changing velocity throughout the manoeuvre is superior to a previous analytical method that assumes constant speed