SREBP1-dependent de novo fatty acid synthesis gene expression is elevated in malignant melanoma and represents a cellular survival trait.

de novo fatty acid biosynthesis (DNFA) is a hallmark adaptation of many cancers that supports survival, proliferation, and metastasis. Here we elucidate previously unexplored aspects of transcription regulation and clinical relevance of DNFA in cancers. We show that elevated expression of DNFA genes is characteristic of many tumor types and correlates with poor prognosis, especially in melanomas. Elevated DNFA gene expression depends on the SREBP1 transcription factor in multiple melanoma cell lines. SREBP1 predominantly binds to the transcription start sites of DNFA genes, regulating their expression by recruiting RNA polymerase II to promoters for productive transcription elongation. We find that SREBP1-regulated DNFA represents a survival trait in melanoma cells, regardless of proliferative state and oncogenic mutation status. Indeed, malignant melanoma cells exhibit elevated DNFA gene expression after the BRAF/MEK signaling pathway is blocked (e.g. by BRAF inhibitors), and DNFA expression remains higher in melanoma cells resistant to vemurafenib treatment than in untreated cells. Accordingly, DNFA pathway inhibition, whether by direct targeting of SREBP1 with antisense oligonucleotides, or through combinatorial effects of multiple DNFA enzyme inhibitors, exerts potent cytotoxic effects on both BRAFi-sensitive and -resistant melanoma cells. Altogether, these results implicate SREBP1 and DNFA enzymes as enticing therapeutic targets in melanomas

The fermion spectrum in braneworld collisions

In braneworld collisions fermions originally localised on one brane can be transferred to another brane, or to a space-time boundary. By modelling branes as scalar field kinks we bounce them off boundaries and study resulting effects according to a braneworld observer. Extending on our previous work, we numerically compute the spectrum of excitations of fermion modes localised on the brane and boundary, in terms of the momentum $k$ along the brane dimensions. We find that the spectrum depends strongly on collision velocity and fermion-scalar coupling. Also, high-momentum modes tend to ``fall off'' the kinks and become delocalised radiation.Comment: 13 pages, 9 figure

Oscillons and quasi-breathers in D+1 dimensions

We study oscillons in D+1 space-time dimensions using a spherically symmetric ansatz. From Gaussian initial conditions, these evolve by emitting radiation, approaching ``quasi-breathers'', near-periodic solutions to the equations of motion. Using a truncated mode expansion, we numerically determine these quasi-breather solutions in 2<D<6 and the energy dependence on the oscillation frequency. In particular, this energy has a minimum, which in turn depends on the number of spatial dimensions. We study the time evolution and lifetimes of the resulting quasi-breathers, and show how generic oscillons decay into these before disappearing altogether. We comment on the apparent absence of oscillons for D>5 and the possibility of stable solutions for D<2.Comment: 18 pages and 18 figure

N-body simulations of star clusters

Two aspects of our recent N-body studies of star clusters are presented: (1) What impact does mass segregation and selective mass loss have on integrated photometry? (2) How well compare results from N-body simulations using NBODY4 and STARLAB/KIRA?Comment: 2 pages, 1 figure with 4 panels (in colour, not well visible in black-and-white; figures screwed in PDF version, ok in postscript; to see further details get the paper source). Conference proceedings for IAUS246 'Dynamical Evolution of Dense Stellar Systems', ed. E. Vesperini (Chief Editor), M. Giersz, A. Sills, Capri, Sept. 2007; v2: references correcte

Interim report on the ground-water resources of Manatee County, Florida

A large part of western Manatee County is devoted to the growing of winter vegetables and citrus fruits. As in most of peninsular Florida, rainfall in the county during the growing season is not sufficient for crop production and large quantites of artesian water are used for irrigation. The large withdrawals of artesian water for irrigation result in a considerable decline of the artesian head in the western part of the county. This seasonal decline of the artesian head has become larger as the withdrawal of artesian water has increased. The lowering of the fresh-water head in some coastal areas in the State has resulted in an infiltration of sea water into the water-bearing formations. The presence of salty water in the artesian aquifer in parts of the coastal area of Manatee County indicates that sea water may also have entered the waterbearing formations in this area as a result of the decline of artesian pressure during the growing season. The purpose of the investigation is to make a detailed study of the geology and ground-water resources of the county, primarily to determine whether salt-water encroachment has occurred or is likely to occur in the coastal area. (PDF contains 38 pages.