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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
A quantum Szilard engine without heat from a thermal reservoir
We study a quantum Szilard engine that is not powered by heat drawn from a
thermal reservoir, but rather by projective measurements. The engine is
constituted of a system , a weight , and a Maxwell
demon , and extracts work via measurement-assisted feedback
control. By imposing natural constraints on the measurement and feedback
processes, such as energy conservation and leaving the memory of the demon
intact, we show that while the engine can function without heat from a thermal
reservoir, it must give up at least one of the following features that are
satisfied by a standard Szilard engine: (i) repeatability of measurements; (ii)
invariant weight entropy; or (iii) positive work extraction for all measurement
outcomes. This result is shown to be a consequence of the Wigner-Araki-Yanase
(WAY) theorem, which imposes restrictions on the observables that can be
measured under additive conservation laws. This observation is a first-step
towards developing "second-law-like" relations for measurement-assisted
feedback control beyond thermality
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 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.
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