Joseph Silk

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:

We present a multi-wavelength photometric study of 15,000 resolved stars in the nearby spiral galaxy M83 (NGC5236, D = 4.61Mpc) based on Hubble Space Telescope Wide Field Camera 3 observations using four filters:F336W, F438W, F555W, and F814W. We select 50 regions (an average size of 260pc by 280pc) in the spiral arm and inter-arm areas of M83 and determine the age distribution of the luminous stellar populations in each region. This is accomplished by correcting for extinction toward each individual star by comparing its colors with predictions from stellar isochrones. We compare the resulting luminosity-weighted mean ages of the luminous stars in the 50 regions with those determined from several independent methods, including the number ratio of red-to-blue supergiants, morphological appearance of the regions, surface brightness fluctuations, and the ages of clusters in the regions. We find reasonably good agreement between these methods. We also find that young stars are much more likely to be found in concentrated aggregates along spiral arms, while older stars are more dispersed. These results are consistent with the scenario that star formation is associated with the spiral arms, and stars form primarily in star clusters and then disperse on short timescales to form the field population. The locations of Wolf-Rayet stars are found to correlate with the positions of many of the youngest regions, providing additional support for our ability to accurately estimate ages. We address the effects of spatial resolution on the measured colors, magnitudes, and age estimates. While individual stars can occasionally show measurable differences in the colors and magnitudes, the age estimates for entire regions are only slightly affected. © 2012. The American Astronomical Society. All rights reserved.

Abstract:

Supermassive black holes (BH) are powerful sources of energy that are already in place at very early epochs of the Universe (by z=6). Using hydrodynamical simulations of the formation of a massive M_vir=5 10^11 M_sun halo by z=6 (the most massive progenitor of a cluster of M_vir=2 10^15 M_sun at z=0), we evaluate the impact of Active Galactic Nuclei (AGN) on galaxy mass content, BH self-regulation, and gas distribution inside this massive halo. We find that SN feedback has a marginal influence on the stellar structure, and no influence on the mass distribution on large scales. In contrast, AGN feedback alone is able to significantly alter the stellar-bulge mass content by quenching star formation when the BH is self-regulating, and by depleting the cold gas reservoir in the centre of the galaxy. The growth of the BH proceeds first by a rapid Eddington-limited period fed by direct cold filamentary infall. When the energy delivered by the AGN is sufficiently large to unbind the cold gas of the bulge, the accretion of gas onto the BH is maintained both by smooth gas inflow and clump migration through the galactic disc triggered by merger-induced torques. The feedback from the AGN has also a severe consequence on the baryon mass content within the halo, producing large-scale hot superwinds, able to blow away some of the cold filamentary material from the centre and reduce the baryon fraction by more than 30 per cent within the halo's virial radius. Thus in the very young universe, AGN feedback is likely to be a key process, shaping the properties of the most massive galaxies.