2,535 research outputs found
Highly Differentiated Human Fetal RPE Cultures Are Resistant to the Accumulation and Toxicity of Lipofuscin-Like Material
PURPOSE. The accumulation of undigestible autofluorescent material (UAM), termed lipofuscin
in vivo, is a hallmark of aged RPE. Lipofuscin derives, in part, from the incomplete degradation
of phagocytized photoreceptor outer segments (OS). Whether this accumulated waste is toxic
is unclear. We therefore investigated the effects of UAM in highly differentiated human fetal
RPE (hfRPE) cultures.
METHODS. Unmodified and photo-oxidized OS were fed daily to confluent cultures of ARPE-19
RPE or hfRPE. The emission spectrum, composition, and morphology of resulting UAM were
measured and compared to in vivo lipofuscin. Effects of UAM on multiple RPE phenotypes
were assessed.
RESULTS. Compared to ARPE-19, hfRPE were markedly less susceptible to UAM buildup.
Accumulated UAM in hfRPE initially resembled the morphology of lipofuscin from AMD eyes,
but compacted and shifted spectrum over time to resemble lipofuscin from healthy aged
human RPE. UAM accumulation mildly reduced transepithelial electrical resistance,
ketogenesis, certain RPE differentiation markers, and phagocytosis efficiency, while inducing
senescence and rare, focal pockets of epithelial-mesenchymal transition. However, it had no
effects on mitochondrial oxygen consumption rate, certain other RPE differentiation markers,
secretion of drusen components or polarity markers, nor cell death.
CONCLUSIONS. hfRPE demonstrates a remarkable resistance to UAM accumulation, suggesting
mechanisms for efficient OS processing that may be lost in other RPE culture models.
Furthermore, while UAM alters hfRPE phenotype, the effects are modest, consistent with
conflicting reports in the literature on the toxicity of lipofuscin. Our results suggest that
healthy RPE may adequately adapt to and tolerate lipofuscin accumulation
On the upstream mobility scheme for two-phase flow in porous media
When neglecting capillarity, two-phase incompressible flow in porous media is
modelled as a scalar nonlinear hyperbolic conservation law. A change in the
rock type results in a change of the flux function. Discretizing in
one-dimensional with a finite volume method, we investigate two numerical
fluxes, an extension of the Godunov flux and the upstream mobility flux, the
latter being widely used in hydrogeology and petroleum engineering. Then, in
the case of a changing rock type, one can give examples when the upstream
mobility flux does not give the right answer.Comment: A preprint to be published in Computational Geoscience
The terminology of clinical reasoning in health professions education: Implications and considerations
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits
The WWgamma triple gauge boson coupling parameters are studied using p-pbar
-> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were
collected with the DO detector from an integrated luminosity of 162 pb^{-1}
delivered by the Fermilab Tevatron Collider. The cross section times branching
fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV
and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum)
pb. The one-dimensional 95% confidence level limits on anomalous couplings are
-0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events
We present a measurement of the top quark pair ttbar production cross section
in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1}
of data collected by the DO detector at the Fermilab Tevatron Collider. We
select events with one charged lepton (electron or muon), large missing
transverse energy, and at least four jets, and extract the ttbar content of the
sample based on the kinematic characteristics of the events. For a top quark
mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1}
(syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let
Measurement of the B0_s semileptonic branching ratio to an orbitally excited D_s** state, Br(B0_s -> Ds1(2536) mu nu)
In a data sample of approximately 1.3 fb-1 collected with the D0 detector
between 2002 and 2006, the orbitally excited charm state D_s1(2536) has been
observed with a measured mass of 2535.7 +/- 0.6 (stat) +/- 0.5 (syst) MeV via
the decay mode B0_s -> D_s1(2536) mu nu X. A first measurement is made of the
branching ratio product Br(b(bar) -> D_s1(2536) mu nu X).Br(D_s1(2536)->D*
K0_S). Assuming that D_s1(2536) production in semileptonic decay is entirely
from B0_s, an extraction of the semileptonic branching ratio Br(B0_s ->
D_s1(2536) mu nu X) is made.Comment: 7 pages, 2 figures, LaTeX, version with minor changes as accepted by
Phys. Rev. Let
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging
We present a measurement of the top quark pair () production cross
section () in collisions at TeV
using 230 pb of data collected by the D0 experiment at the Fermilab
Tevatron Collider. We select events with one charged lepton (electron or muon),
missing transverse energy, and jets in the final state. We employ
lifetime-based b-jet identification techniques to further enhance the
purity of the selected sample. For a top quark mass of 175 GeV, we
measure pb, in
agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let
Simultaneous measurement of the ratio B(t->Wb)/B(t->Wq) and the top quark pair production cross section with the D0 detector at sqrt(s)=1.96 TeV
We present the first simultaneous measurement of the ratio of branching
fractions, R=B(t->Wb)/B(t->Wq), with q being a d, s, or b quark, and the top
quark pair production cross section sigma_ttbar in the lepton plus jets channel
using 0.9 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV collected with the
D0 detector. We extract R and sigma_ttbar by analyzing samples of events with
0, 1 and >= 2 identified b jets. We measure R = 0.97 +0.09-0.08 (stat+syst) and
sigma_ttbar = 8.18 +0.90-0.84 (stat+syst)} +/-0.50 (lumi) pb, in agreement with
the standard model prediction.Comment: submitted to Phys.Rev.Letter
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