539 research outputs found
An oncogenic role for sphingosine kinase 2
While both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an antiproliferative/ pro-apoptotic function for SK2, while others indicate it has a prosurvival role and its inhibition can have anti-cancer effects. Our analysis of gene expression data revealed that SK2 is upregulated in many human cancers, but only to a small extent (up to 2.5-fold over normal tissue). Based on these findings, we examined the effect of different levels of cellular SK2 and showed that high-level overexpression reduced cell proliferation and survival, and increased cellular ceramide levels. In contrast, however, low-level SK2 overexpression promoted cell survival and proliferation, and induced neoplastic transformation in vivo. These findings coincided with decreased nuclear localization and increased plasma membrane localization of SK2, as well as increases in extracellular S1P formation. Hence, we have shown for the first time that SK2 can have a direct role in promoting oncogenesis, supporting the use of SK2-specific inhibitors as anti-cancer agents.Heidi A. Neubauer, Duyen H. Pham, Julia R. Zebol, Paul A.B. Moretti, Amanda L. Peterson, Tamara M. Leclercq, Huasheng Chan, Jason A. Powell, Melissa R. Pitman, Michael S. Samuel, Claudine S. Bonder, Darren J. Creek, Briony L. Gliddon and Stuart M. Pitso
Evaluating potential effects of solar power facilities on wildlife from an animal behavior perspective
Solar power is a renewable energy source with great potential to help meetincreasing global energy demands and reduce our reliance on fossil fuels.However, research is scarce on how solar facilities affect wildlife. With inputfrom professionals in ecology, conservation, and energy, we conducted aresearch-prioritization process and identified key questions needed to betterunderstand impacts of solar facilities on wildlife. We focused on animalbehavior, which can be used to identify population responses before mortal-ity or other fitness consequences are documented. Behavioral studies canalso offer approaches to understand the mechanisms leading to negativeinteractions (e.g., collision, singeing, avoidance) and provide insight into mit-igating effects. Here, we review how behavioral responses to solar facilities, including perception, movement, habitat use, and interspecific interactionsare priority research areas. Addressing these themes will lead to a morecomprehensive understanding of the effects of solar power on wildlife andguide future mitigatio
The carpase-like sites of proteasomes: substrate specificity, new inhibitors and substrates, and allosteric interactions with the trypsin-like sites
Bio-Organische synthes
Harnessing plant biomass for biofuels and biomaterials
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72519/1/j.1365-313X.2008.03512.x.pd
Measuring Black Hole Spin using X-ray Reflection Spectroscopy
I review the current status of X-ray reflection (a.k.a. broad iron line)
based black hole spin measurements. This is a powerful technique that allows us
to measure robust black hole spins across the mass range, from the stellar-mass
black holes in X-ray binaries to the supermassive black holes in active
galactic nuclei. After describing the basic assumptions of this approach, I lay
out the detailed methodology focusing on "best practices" that have been found
necessary to obtain robust results. Reflecting my own biases, this review is
slanted towards a discussion of supermassive black hole (SMBH) spin in active
galactic nuclei (AGN). Pulling together all of the available XMM-Newton and
Suzaku results from the literature that satisfy objective quality control
criteria, it is clear that a large fraction of SMBHs are rapidly-spinning,
although there are tentative hints of a more slowly spinning population at high
(M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of
the spins of stellar-mass black holes in X-ray binaries. In general,
reflection-based and continuum-fitting based spin measures are in agreement,
although there remain two objects (GROJ1655-40 and 4U1543-475) for which that
is not true. I end this review by discussing the exciting frontier of
relativistic reverberation, particularly the discovery of broad iron line
reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and
MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk
reflection, this detection of reverberation demonstrates that future large-area
X-ray observatories such as LOFT will make tremendous progress in studies of
strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The
Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds
a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the
referencing of the discovery of soft lags in 1H0707-495 (which were in fact
first reported in Fabian et al. 2009
A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses
We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants
Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector
The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg
array of high purity germanium detectors housed in an ultra-low background
shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA
DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while
demonstrating the feasibility of a tonne-scale experiment. It may also carry
out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that
customized Broad Energy Germanium (BEGe) detectors produced by Canberra have
several desirable features for a neutrinoless double-beta decay experiment,
including low electronic noise, excellent pulse shape analysis capabilities,
and simple fabrication. We have deployed a customized BEGe, the MAJORANA
Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and
shield at the Kimballton Underground Research Facility in Virginia. This paper
will focus on the detector characteristics and measurements that can be
performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure
Inclusive eta' Production from the Upsilon(1S)
Using the CLEO II detector at CESR, we measure the eta' - gluon - gluon
form-factor in Y(1S) decays. This form-factor especially at large eta' energies
may provide an explanation of the large rate for B -> Xs eta'. Our data do not
support a large anomalous coupling at higher q^2 and thus the large eta' rate
remains a mystery, possibly requiring a non-Standard Model explanation.Comment: 14 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Active Galactic Nuclei at the Crossroads of Astrophysics
Over the last five decades, AGN studies have produced a number of spectacular
examples of synergies and multifaceted approaches in astrophysics. The field of
AGN research now spans the entire spectral range and covers more than twelve
orders of magnitude in the spatial and temporal domains. The next generation of
astrophysical facilities will open up new possibilities for AGN studies,
especially in the areas of high-resolution and high-fidelity imaging and
spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These
studies will address in detail a number of critical issues in AGN research such
as processes in the immediate vicinity of supermassive black holes, physical
conditions of broad-line and narrow-line regions, formation and evolution of
accretion disks and relativistic outflows, and the connection between nuclear
activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic
Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical
Symposia Serie
Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|
We report on determinations of |Vub| resulting from studies of the branching
fraction and q^2 distributions in exclusive semileptonic B decays that proceed
via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson
pairs collected at the Y(4S) resonance with the CLEO II detector. We measure
B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 ->
rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the
errors are statistical, experimental systematic, systematic due to residual
form-factor uncertainties in the signal, and systematic due to residual
form-factor uncertainties in the cross-feed modes, respectively. We also find
B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with
what is expected from the B -> pi l nu mode and quark model symmetries. We
extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and
Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals
yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu,
and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu,
where the errors are statistical, experimental systematic, theoretical, and
signal form-factor shape, respectively. Our combined value from both decay
modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
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