911 research outputs found
Methylation of Wnt7a Is Modulated by DNMT1 and Cigarette Smoke Condensate in Non-Small Cell Lung Cancer
Wnt7a is known to be a tumor suppressor that is lost in NSCLC, but no mechanism of loss has been established. Methylation of promoter regions has been established as a common mechanism of loss of tumor suppressor expression in NSCLC. We previously demonstrated that loss of Wnt7a in non-transformed lung epithelial cell lines led to increased cell growth, altered 3-D culture growth, and increased migration. The Wnt7a promoter has a higher percentage of methylation in NSCLC tumor tissue compared to matched normal lung tissue and methylation of the promoter region leads to decreased activity. We treated H157 and H1299 NSCLC cell lines with 5-Aza-2′-deoxycytidine and detected loss of Wnt7a promoter methylation, increased Wnt7a expression, and increased activity of the Wnt7a lung signaling pathway. When DNMT1 expression was knocked down by shRNA, expression of Wnt7a increased and methylation decreased. Together these data suggest that in NSCLC, Wnt7a is lost by methylation in a subset of tumors and that this methylation is maintained by DNMT1. Restoration of Wnt7a expression through demethylation could be an important therapeutic approach in the treatment of NSCLC
The pedunculopontine tegmental nucleus and the nucleus basalis magnocellularis: Do both have a role in sustained attention?
It is well established that nucleus basalis magnocellularis (NbM) lesions impair performance on tests of sustained attention. Previous work from this laboratory has also demonstrated that pedunculopontine tegmental nucleus (PPTg) lesioned rats make more omissions on a test of sustained attention, suggesting that it might also play a role in mediating this function. However, the results of the PPTg study were open to alternative interpretation. We aimed to resolve this by conducting a detailed analysis of the effects of damage to each brain region in the same sustained attention task used in our previous work. Rats were trained in the task before surgery and post-surgical testing examined performance in response to unpredictable light signals of 1500 ms and 4000 ms duration. Data for PPTg lesioned rats were compared to control rats, and rats with 192 IgG saporin infusions centred on the NbM. In addition to operant data, video data of rats' performance during the task were also analysed
Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers
We present a review of the interplay between the evolution of circumstellar
disks and the formation of planets, both from the perspective of theoretical
models and dedicated observations. Based on this, we identify and discuss
fundamental questions concerning the formation and evolution of circumstellar
disks and planets which can be addressed in the near future with optical and
infrared long-baseline interferometers. Furthermore, the importance of
complementary observations with long-baseline (sub)millimeter interferometers
and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics
Review"; The final publication is available at http://www.springerlink.co
Planetary population synthesis
In stellar astrophysics, the technique of population synthesis has been
successfully used for several decades. For planets, it is in contrast still a
young method which only became important in recent years because of the rapid
increase of the number of known extrasolar planets, and the associated growth
of statistical observational constraints. With planetary population synthesis,
the theory of planet formation and evolution can be put to the test against
these constraints. In this review of planetary population synthesis, we first
briefly list key observational constraints. Then, the work flow in the method
and its two main components are presented, namely global end-to-end models that
predict planetary system properties directly from protoplanetary disk
properties and probability distributions for these initial conditions. An
overview of various population synthesis models in the literature is given. The
sub-models for the physical processes considered in global models are
described: the evolution of the protoplanetary disk, the planets' accretion of
solids and gas, orbital migration, and N-body interactions among concurrently
growing protoplanets. Next, typical population synthesis results are
illustrated in the form of new syntheses obtained with the latest generation of
the Bern model. Planetary formation tracks, the distribution of planets in the
mass-distance and radius-distance plane, the planetary mass function, and the
distributions of planetary radii, semimajor axes, and luminosities are shown,
linked to underlying physical processes, and compared with their observational
counterparts. We finish by highlighting the most important predictions made by
population synthesis models and discuss the lessons learned from these
predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the
'Handbook of Exoplanets', planet formation section, section editor: Ralph
Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed
Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV
We use 106 \ipb of data collected with the Collider Detector at Fermilab to
search for narrow-width, vector particles decaying to a top and an anti-top
quark. Model independent upper limits on the cross section for narrow, vector
resonances decaying to \ttbar are presented. At the 95% confidence level, we
exclude the existence of a leptophobic \zpr boson in a model of
topcolor-assisted technicolor with mass M_{\zpr} 480 \gev for natural
width = 0.012 M_{\zpr}, and M_{\zpr} 780 \gev for =
0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200
Double Diffraction Dissociation at the Fermilab Tevatron Collider
We present results from a measurement of double diffraction dissociation in
collisions at the Fermilab Tevatron collider. The production cross
section for events with a central pseudorapidity gap of width
(overlapping ) is found to be [] at [630]
GeV. Our results are compared with previous measurements and with predictions
based on Regge theory and factorization.Comment: 10 pages, 4 figures, using RevTeX. Submitted to Physical Review
Letter
Search for Gluinos and Scalar Quarks in Collisions at TeV using the Missing Energy plus Multijets Signature
We have performed a search for gluinos (\gls) and squarks (\sq) in a data
sample of 84 pb of \ppb collisions at = 1.8 TeV, recorded by
the Collider Detector at Fermilab, by investigating the final state of large
missing transverse energy and 3 or more jets, a characteristic signature in
R-parity-conserving supersymmetric models. The analysis has been performed
`blind', in that the inspection of the signal region is made only after the
predictions from Standard Model backgrounds have been calculated. Comparing the
data with predictions of constrained supersymmetric models, we exclude gluino
masses below 195 \gev (95% C.L.), independent of the squark mass. For the case
\msq \approx \mgls, gluino masses below 300 \gev are excluded.Comment: 7 pages, 3 figure
Search for Kaluza-Klein Graviton Emission in Collisions at TeV using the Missing Energy Signature
We report on a search for direct Kaluza-Klein graviton production in a data
sample of 84 of \ppb collisions at = 1.8 TeV, recorded
by the Collider Detector at Fermilab. We investigate the final state of large
missing transverse energy and one or two high energy jets. We compare the data
with the predictions from a -dimensional Kaluza-Klein scenario in which
gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for
=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71
TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure
Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF
If the Technicolor omega_T particle exists, a likely decay mode is omega_T ->
gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We
have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab
Tevatron for events with a photon and two jets, where one of the jets must
contain a secondary vertex implying the presence of a b quark. We find no
excess of events above standard model expectations. We express the result of an
exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs):
http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps
FERMILAB-PUB-98/321-
Domain Swapping and Different Oligomeric States for the Complex Between Calmodulin and the Calmodulin-Binding Domain of Calcineurin A
BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that engages in regulatory interactions with a large number of cellular proteins. Previously, a unique mode of CaM target recognition has been observed in the crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A in a novel crystal form, which shows a dimeric assembly of calmodulin, as observed before in the crystal state. We note that the conformation of CaM in this complex is very similar to that of unliganded CaM, and a detailed analysis revels that the CaM-binding motif in calcineurin A is of a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show that the complex is fully monomeric in solution, and a structure of a canonically collapsed CaM-peptide complex can easily be fitted into the SAXS data. This result is also supported by size exclusion chromatography, where the addition of the ligand peptide decreases the apparent size of CaM. In addition, we studied the energetics of binding by isothermal titration calorimetry and found them to closely resemble those observed previously for ligand peptides from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2 arrangement in the crystal state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1 complexes will require domain swapping in CaM, accompanied by the characteristic bending of the central linker helix between the two lobes of CaM
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