Retroviral transduction of peptide stimulated t cells can generate dual t cell receptor-expressing (bifunctional) t cells reactive with two defined antigens

BACKGROUND: Tumors and viruses have developed many mechanisms to evade the immune system, including down-regulation of target antigens and MHC molecules. These immune escape mechanisms may be able to be circumvented by adoptively transferring T cells engineered to express two different T cell receptors, each specific for a different antigen or MHC restriction molecule. METHODS: PBMC from the blood of normal healthy donors were stimulated for three days with an antigenic peptide from cytomegalovirus (CMV) pp65. These CMV reactive cultures were transduced with a encoding the TIL 5 T cell receptor (TCR) that mediates recognition of the dominant epitope of the melanoma antigen MART-1. Following selection for transduced cells, the cultures were evaluated for recognition of CMV pp65 and MART-1 expressing targets. RESULTS: We were able to rapidly create bifunctional T cells capable of recognizing both CMV pp65 and MART-1 using a combination of HLA-A2 tetramer staining and intracellular staining for interferon-γ. These bifunctional T cells were sensitive to very low levels of antigen, recognize MART-1(+ )tumor cells, and maintained their bifunctionality for over 40 days in culture. CONCLUSION: Bifunctional T cells can be engineered by transducing short term peptide stimulated T cell cultures. These bifunctional T cells may be more effective in treating patients with cancer or chronic virus infections because they would reduce the possibility of disease progression due to antigen and/or MHC loss variants

An Alternative Interpretation of Statistical Mechanics

In this paper I propose an interpretation of classical statistical mechanics that centers on taking seriously the idea that probability measures represent complete states of statistical mechanical systems. I show how this leads naturally to the idea that the stochasticity of statistical mechanics is associated directly with the observables of the theory rather than with the microstates (as traditional accounts would have it). The usual assumption that microstates are representationally significant in the theory is therefore dispensable, a consequence which suggests interesting possibilities for developing non-equilibrium statistical mechanics and investigating inter-theoretic answers to the foundational questions of statistical mechanics

Modeling partial discharge in a three-phase cable joint experiment with minimal adjustable parameters

A general physical model of partial discharge (PD) has been developed and used to simulate discharges within a void at the tip of a metallic spike defect within a three-phase 11 kV paper insulated lead covered (PILC) cable joint. Discharges are modeled by altering surface charge density at the void boundary using a logistic function distribution. The model was validated against experimental data, and a good agreement was observed with minimal free parameters. The model was then used to investigate the impact of single phase energization on PD activity in three-phase PILC cable joints. It was concluded that PD testing of three-phase PILC cable joints should be performed at raised temperatures with the cable fully energized as this results in a higher frequency of PD activity, and reduces the level of background PD from cable terminations. This research represents a further step towards developing PD models that can describe measurements taken from operational high voltage plant

The privilege of choice: how prospective college students’ financial concerns influence their choice of higher education institution and subject of study in England

A hallmark of English higher education (HE) over the last twenty years has been policies seeking to increase provider competition and student choice. Central to this has been student funding policy changes, leading to rising college costs. This article asks if prospective HE students’ concerns about college costs and the financial strategies they anticipate using because of them, widen or limit their choice of HE institution and subject of study. It calls on the findings from a nationally representative survey of 1,374 English college applicants and uses latent class analysis to develop a typology of students’ planned financial coping mechanisms: Minimizing costs; Managing costs and maximizing returns; and No financial concerns; which prove to be socially stratified. Minimizing costs students are the most disadvantaged and adopt mechanisms which constrain their choices of where and what to study, unlike students in the other groups. Thus, government policies aimed at improving student choice potentially have the opposite effect for the most disadvantaged, perpetuating existing inequalities in access to, and the experience of, HE

Higher education, mature students and employment goals: policies and practices in the UK

This article considers recent policies of Higher Education in the UK, which are aimed at widening participation and meeting the needs of employers. The focus is on the growing population of part-time students, and the implications of policies for this group. The article takes a critical perspective on government policies, using data from a major study of mature part-time students, conducted in two specialist institutions in the UK, a London University college and a distance learning university. Findings from this study throw doubt on the feasibility of determining a priori what kind of study pathway is most conducive for the individual in terms of employment gains and opportunities for upward social mobility. In conclusion, doubts are raised as to whether policies such as those of the present UK government are likely to achieve its aims. Such policies are not unique to the UK, and lessons from this country are relevant to most of the developed world

Applications of DFT to the theory of twentieth-century harmony

Music theorists have only recently, following groundbreaking work by Quinn, recognized the potential for the DFT on pcsets, initially proposed by Lewin, to serve as the foundation of a theory of harmony for the twentieth century. This paper investigates pcset “arithmetic” – subset structure, transpositional combination, and interval content – through the lens of the DFT. It discusses relationships between interval classes and DFT magnitudes, considers special properties of dyads, pcset products, and generated collections, and suggest methods of using the DFT in analysis, including interpreting DFT magnitudes, using phase spaces to understand subset structure, and interpreting the DFT of Lewin’s interval function. Webern’s op. 5/4 and Bartok’s String Quartet 4, iv, are discussed.Accepted manuscrip

Higher education and mental health: analyses of the LSYPE cohorts

The aim of our research project was to improve our understanding of common mental health problems in young people who attend higher education, compared with those who do not. We investigated: • whether there were differences in symptoms of common mental disorder between these groups; • how these differences changed over time and what might drive them; and • whether the mental health of higher education students compared with the general population has changed during the past decade. We conducted analyses of two large nationally representative cohort studies: the Longitudinal Studies of Young People In England (LSYPE). Both studies started when young people were 13/14 years of age. LSYPE1, known to participants as Next Steps, started in 2004 and LSYPE2, known to participants as Our Future, started in 2013

T and CPT Symmetries in Entangled Neutral Meson Systems

Genuine tests of an asymmetry under T and/or CPT transformations imply the interchange between in-states and out-states. I explain a methodology to perform model-indepedent separate measurements of the three CP, T and CPT symmetry violations for transitions involving the decay of the neutral meson systems in B- and {\Phi}-factories. It makes use of the quantum-mechanical entanglement only, for which the individual state of each neutral meson is not defined before the decay of its orthogonal partner. The final proof of the independence of the three asymmetries is that no other theoretical ingredient is involved and that the event sample corresponding to each case is different from the other two. The experimental analysis for the measurements of these three asymmetries as function of the time interval {\Delta}t > 0 between the first and second decays is discussed, as well as the significance of the expected results. In particular, one may advance a first observation of true, direct, evidence of Time-Reserval-Violation in B-factories by many standard deviations from zero, without any reference to, and independent of, CP-Violation. In some quantum gravity framework the CPT-transformation is ill-defined, so there is a resulting loss of particle-antiparticle identity. This mechanism induces a breaking of the EPR correlation in the entanglement imposed by Bose statistics to the neutral meson system, the so-called {\omega}-effect. I present results and prospects for the {\omega}-parameter in the correlated neutral meson-antimeson states.Comment: Proc. DISCRETE 2010, Symposium on Prospects in the Physics of Discrete Symmetries, December 2010, Rom