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G-TRACE: rapid Gal4-based cell lineage analysis in Drosophila.
We combined Gal4-UAS and the FLP recombinase-FRT and fluorescent reporters to generate cell clones that provide spatial, temporal and genetic information about the origins of individual cells in Drosophila melanogaster. We named this combination the Gal4 technique for real-time and clonal expression (G-TRACE). The approach should allow for screening and the identification of real-time and lineage-traced expression patterns on a genomic scale
Quasi-Single Field Inflation with Large Mass
We study the effect of massive isocurvaton on density perturbations in
quasi-single field inflation models, when the mass of the isocurvaton M becomes
larger than the order of the Hubble parameter H. We analytically compute the
correction to the power spectrum, leading order in coupling but exact for all
values of mass. This verifies the previous numerical results for the range
0<M<3H/2 and shows that, in the large mass limit, the correction is of order
H^2/M^2.Comment: 19 pages, 6 figures; v2: minor revisio
Genetic and epigenetic analyses of MBD3 in colon and lung cancer
MBD3: is a member of the methyl-CpG-binding domain family and is located on chromosome 19p13.3, a region of loss of heterozygosity in colon and lung cancers. We therefore screened samples for abnormalities in MBD3. Our results indicate that MBD3 is not a major target of genetic and epigenetic alteration in these cancers.Publisher PDFPeer reviewe
Change in longitudinal trends in sleep quality and duration following breast cancer diagnosis: results from the Women's Health Initiative
Breast cancer survivors frequently report sleep problems, but little research has studied sleep patterns longitudinally. We examined trends in sleep quality and duration up to 15 years before and 20 years after a diagnosis of breast cancer, over time among postmenopausal women participating in the Women's Health Initiative (WHI). We included 12,098 participants who developed invasive breast cancer after study enrollment. A linear mixed-effects model was used to determine whether the time trend in sleep quality, as measured by the WHI Insomnia Rating Scale (WHIIRS), a measure of perceived insomnia symptoms from the past 4 weeks, changed following a cancer diagnosis. To examine sleep duration, we fit a logistic regression model with random effects for both short (<6 h) and long (≥9 h) sleep. In addition, we studied the association between depressive symptoms and changes in WHIIRS and sleep duration. There was a significantly slower increase in the trend of WHIIRS after diagnosis (β = 0.06; p = 0.03), but there were non-significant increases in the trend of the probability of short or long sleep after diagnosis. The probability of depressive symptoms significantly decreased, though the decrease was more pronounced after diagnosis (p < 0.01). Trends in WHIIRS worsened at a relatively slower rate following diagnosis and lower depression rates may explain the slower worsening in WHIIRS. Our findings suggest that over a long period of time, breast cancer diagnosis does not adversely affect sleep quality and duration in postmenopausal women compared to sleep pre-diagnosis, yet both sleep quality and duration continue to worsen over time.WHI - National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]; Ohio State University Susan G Komen Graduate Trainee Program [GTDR15334082]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Effective theories of single field inflation when heavy fields matter
We compute the low energy effective field theory (EFT) expansion for
single-field inflationary models that descend from a parent theory containing
multiple other scalar fields. By assuming that all other degrees of freedom in
the parent theory are sufficiently massive relative to the inflaton, it is
possible to derive an EFT valid to arbitrary order in perturbations, provided
certain generalized adiabaticity conditions are respected. These conditions
permit a consistent low energy EFT description even when the inflaton deviates
off its adiabatic minimum along its slowly rolling trajectory. By generalizing
the formalism that identifies the adiabatic mode with the Goldstone boson of
this spontaneously broken time translational symmetry prior to the integration
of the heavy fields, we show that this invariance of the parent theory dictates
the entire non-perturbative structure of the descendent EFT. The couplings of
this theory can be written entirely in terms of the reduced speed of sound of
adiabatic perturbations. The resulting operator expansion is distinguishable
from that of other scenarios, such as standard single inflation or DBI
inflation. In particular, we re-derive how certain operators can become
transiently strongly coupled along the inflaton trajectory, consistent with
slow-roll and the validity of the EFT expansion, imprinting features in the
primordial power spectrum, and we deduce the relevant cubic operators that
imply distinct signatures in the primordial bispectrum which may soon be
constrained by observations.Comment: (v1) 25 pages, 1 figure; (v2) references added and typos corrected,
to appear in Journal of High Energy Physic
Large non-Gaussian Halo Bias from Single Field Inflation
We calculate Large Scale Structure observables for non-Gaussianity arising
from non-Bunch-Davies initial states in single field inflation. These scenarios
can have substantial primordial non-Gaussianity from squeezed (but observable)
momentum configurations. They generate a term in the halo bias that may be more
strongly scale-dependent than the contribution from the local ansatz. We also
discuss theoretical considerations required to generate an observable
signature.Comment: 30 pages, 14 figures, typos corrected and minor changes to match
published version JCAP09(2012)00
Stochastic Gravity: A Primer with Applications
Stochastic semiclassical gravity of the 90's is a theory naturally evolved
from semiclassical gravity of the 70's and 80's. It improves on the
semiclassical Einstein equation with source given by the expectation value of
the stress-energy tensor of quantum matter fields in curved spacetimes by
incorporating an additional source due to their fluctuations. In stochastic
semiclassical gravity the main object of interest is the noise kernel, the
vacuum expectation value of the (operator-valued) stress-energy bi-tensor, and
the centerpiece is the (stochastic) Einstein-Langevin equation. We describe
this new theory via two approaches: the axiomatic and the functional. The
axiomatic approach is useful to see the structure of the theory from the
framework of semiclassical gravity. The functional approach uses the
Feynman-Vernon influence functional and the Schwinger-Keldysh close-time-path
effective action methods which are convenient for computations. It also brings
out the open systems concepts and the statistical and stochastic contents of
the theory such as dissipation, fluctuations, noise and decoherence. We then
describe the application of stochastic gravity to the backreaction problems in
cosmology and black hole physics. Intended as a first introduction to this
subject, this article places more emphasis on pedagogy than completeness.Comment: 46 pages Latex. Intended as a review in {\it Classical and Quantum
Gravity
Data to support study of The Spin States of Diastereomeric Iron(II)/Bis[2,6-Di(thiazolin-2-yl)-pyridine] (ThioPyBox) Complexes, and a Comparison with the Corresponding PyBox Derivatives
Diastereomeric [Fe(L1R)2][ClO4]2 (R = Ph, iPr) iron(II)/ThioPyBox derivatives show a larger discrimination of their spin states than the corresponding [Fe(L2R)2][ClO4]2 PyBox complexe
Data to support study of Heteroleptic Iron(II) Complexes of Chiral 2,6-Bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-Bis(thiazolin-2-yl)pyridine Ligands ‒ the Interplay of Two Different Ligands on the Metal Ion Spin State
The spin-crossover properties of [Fe(LR)L][ClO4]2 (LR = a chiral PyBox {L1R} or ThioPyBox {L2R} derivative) show subtle differences depending on the tridentate ‘L’ co-ligand
Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EGFR-mutant tumors.
The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs).
We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs.
In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR, and ERBB2), we discovered novel fusions and recurrently mutated genes, including ATF7IP, a regulator of gene expression, that was inactivated in 5% of primary LuAD cases. We also found germline mutations at dominant familiar-cancer genes, highlighting the importance of genetic predisposition in the origin of a subset of NSK-LuADs. Furthermore, there was an over-representation of inactivating alterations at RB1, mostly through complex intragenic rearrangements, in treatment-naive EGFR-mutant LuADs. Three EGFR-mutant and one EGFR-wild-type tumors acquired resistance to EGFR-TKIs and chemotherapy, respectively, and histology on re-biopsies revealed the development of small-cell lung cancer/squamous cell carcinoma (SCLC/LuSCC) transformation. These features were consistent with RB1 inactivation and acquired EGFR-T790M mutation or FGFR3-TACC3 fusion in EGFR-mutant tumors.
We found recurrent alterations in LuADs that deserve further exploration. Our work also demonstrates that a subset of NSK-LuADs arises within cancer-predisposition syndromes. The preferential occurrence of RB1 inactivation, via complex rearrangements, found in EGFR-mutant tumors appears to favor SCLC/LuSCC transformation under growth-inhibition pressures. Thus RB1 inactivation may predict the risk of LuAD transformation to a more aggressive type of lung cancer, and may need to be considered as a part of the clinical management of NSK-LuADs patients.This work was supported by the Fundacion Cientifica Asociacion Española Contra el Cancer-AECC (grant number GCB14142170MONT) to LMM, MS-C, and EF; the Spanish Ministry of Economy and Competitivity-MINECO (grant number SAF-2017-82186R to MS-C; Rio Hortega-CM17/00180 to MS; PROYBAR17005NADA to EN); the Health Institute Carlos III-ISCIII, Fondo Europeo de Desarrollo Regional-FEDER (grant Number PT13/0001/0044, PT17/0009/0019, PI16 01821); the Government of Navarra (grant number DIANA project); and the Ramon Areces Foundation (no grant number is applicable) to LMM and RP.S
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