Beecroft Institute for Particle Astrophysics and Cosmology

Abstract:

Monocyte-derived dendritic cells (moDC) have been widely used in cancer immunotherapy but show significant donor-to-donor variability and low capacity for the cross-presentation of tumour-associated antigens (TAA) to CD8(+) T cells, greatly limiting the success of this approach. Given recent developments in induced pluripotency and the relative ease with which induced pluripotent stem (iPS) cell lines may be generated from individuals, we have succeeded in differentiating dendritic cells (DC) from human leukocyte antigen (HLA)-A(*)0201(+) iPS cells (iPS cell-derived DC (ipDC)), using protocols compliant with their subsequent clinical application. Unlike moDC, a subset of ipDC was found to coexpress CD141 and XCR1 that have been shown previously to define the human equivalent of mouse CD8α(+) DC, in which the capacity for cross-presentation has been shown to reside. Accordingly, ipDC were able to cross-present the TAA, Melan A, to a CD8(+) T-cell clone and stimulate primary Melan A-specific responses among naïve T cells from an HLA-A(*)0201(+) donor. Given that CD141(+)XCR1(+) DC are present in peripheral blood in trace numbers that preclude their clinical application, the ability to generate a potentially unlimited source from iPS cells offers the possibility of harnessing their capacity for cross-priming of cytotoxic T lymphocytes for the induction of tumour-specific immune responses.

Abstract:

The peculiar velocities of galaxies are an inherently valuable cosmological probe, providing an unbiased estimate of the distribution of matter on scales much larger than the depth of the survey. Much research interest has been motivated by the high dipole moment of our local peculiar velocity field, which suggests a large-scale excess in the matter power spectrum and can appear to be in some tension with the Λ cold dark matter (ΛCDM) model. We use a composite catalogue of 4537 peculiar velocity measurements with a characteristic depth of 33 h-1Mpc to estimate the matter power spectrum. We compare the constraints with this method, directly studying the full peculiar velocity catalogue, to results by Macaulay et al., studying minimum variance moments of the velocity field, as calculated by Feldman, Watkins & Hudson. We find good agreement with the ΛCDM model on scales of k > 0.01hMpc-1. We find an excess of power on scales of k < 0.01hMpc-1 with a 1σ uncertainty which includes the ΛCDM model. We find that the uncertainty in excess at these scales is larger than an alternative result studying only moments of the velocity field, which is due to the minimum variance weights used to calculate the moments. At small scales, we are able to clearly discriminate between linear and non-linear clustering in simulated peculiar velocity catalogues and find some evidence (although less clear) for linear clustering in the real peculiar velocity data. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.

Abstract:

A unified framework for theories of modified gravity will be an essential tool for interpreting the forthcoming deluge of cosmological data. We present such a formalism, the Parameterized Post-Friedmann framework (PPF), which parameterizes the cosmological perturbation theory of a wide variety of modified gravity models. PPF is able to handle spin-0 degrees of freedom from new scalar, vector and tensor fields, meaning that it is not restricted to simple models based solely on cosmological scalar fields. A direct correspondence is maintained between the parameterization and the underlying space of theories, which allows us to build up a `dictionary' of modified gravity theories and their PPF correspondences. In this paper we describe the construction of the parameterization and demonstrate its use through a number of worked examples relevant to the current literature. We indicate how the formalism will be implemented numerically, so that the dictionary of modified gravity can be pitted against forthcoming observations.