223 research outputs found
Causal inference for continuous-time processes when covariates are observed only at discrete times
Most of the work on the structural nested model and g-estimation for causal
inference in longitudinal data assumes a discrete-time underlying data
generating process. However, in some observational studies, it is more
reasonable to assume that the data are generated from a continuous-time process
and are only observable at discrete time points. When these circumstances
arise, the sequential randomization assumption in the observed discrete-time
data, which is essential in justifying discrete-time g-estimation, may not be
reasonable. Under a deterministic model, we discuss other useful assumptions
that guarantee the consistency of discrete-time g-estimation. In more general
cases, when those assumptions are violated, we propose a controlling-the-future
method that performs at least as well as g-estimation in most scenarios and
which provides consistent estimation in some cases where g-estimation is
severely inconsistent. We apply the methods discussed in this paper to
simulated data, as well as to a data set collected following a massive flood in
Bangladesh, estimating the effect of diarrhea on children's height. Results
from different methods are compared in both simulation and the real
application.Comment: Published in at http://dx.doi.org/10.1214/10-AOS830 the Annals of
Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical
Statistics (http://www.imstat.org
Electronic, optical and transport properties of van der Waals Transition-metal Dichalcogenides Heterostructures: A First-principle Study
Two-dimensional (2D) transition-metal dichalcogenide (TMD) MX (M = Mo, W;
X= S, Se, Te) possess unique properties and novel applications. In this work,
we perform first-principles calculations on the van der Waals (vdW) stacked
MX heterostructures to investigate their electronic, optical and transport
properties systematically. We perform the so-called Anderson's rule to classify
the heterostructures by providing the scheme of the construction of energy band
diagrams for the heterostructure consisting of two semiconductor materials. For
most of the MX heterostructures, the conduction band maximum (CBM) and
valence band minimum (VBM) reside in two separate semiconductors, forming type
II band structure, thus the electron-holes pairs are spatially separated. We
also find strong interlayer coupling at point after forming MX
heterostructures, even leading to the indirect band gap. While the band
structure near point remain as the independent monolayer. The carrier
mobilities of MX heterostructures depend on three decisive factors, elastic
modulus, effective mass and deformation potential constant, which are discussed
and contrasted with those of monolayer MX, respectively.Comment: 7 figure
Strongly interacting Bose-Fermi mixture: mediated interaction, phase diagram and sound propagation
Motivated by recent surprising experimental findings, we develop a
strong-coupling theory for Bose-Fermi mixtures capable of treating resonant
inter-species interactions while satisfying the compressibility sum rule. We
show that the mixture can be stable at large interaction strengths close to
resonance, in agreement with the experiment but at odds with the widely used
perturbation theory. We also calculate the sound velocity of the Bose gas in
the Cs-Li mixture, again finding good agreement with the
experimental observations both at weak and strong interactions. A central
ingredient of our theory is the generalization of a fermion mediated
interaction to strong Bose-Fermi scatterings and to finite frequencies. This
further leads to a predicted hybridization of the sound modes of the Bose and
Fermi gases, which can be directly observed using Bragg spectroscopy.Comment: 13 pages, 10 figure
Knockdown of Brm and Baf170, Components of Chromatin Remodeling Complex, Facilitates Reprogramming of Somatic Cells
© Copyright 2015, Mary Ann Liebert, Inc. 2015. The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells, esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. In this study, we sought to determine whether Brm and Baf170 play any roles in induced pluripotent stem cell (iPSC) reprogramming by using shRNA-mediated knockdown studies in the mouse model. We found that knocking down Brm during early, mid, and late stages (days 3, 6, and 9 after initial iPSC induction) and knocking down Baf170 during late-stage (day 9) reprogramming improve the numbers of iPSC colonies formed. We further showed that inhibition of these somatic BAF components also promotes complete reprogramming of partially reprogrammed somatic cells (pre-iPSCs). Finally, we found that the expression of Brm and Baf170 during reprogramming was regulated by Jak/Stat3 activity. Taken together, these data suggest that inhibiting somatic BAF improves complete reprogramming by facilitating the activation of the pluripotency circuitry
Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells.
When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate whether such SP cells had features associated with epithelial stem cells. Human and rabbit limbal-corneal and conjunctival epithelial cells were incubated with Hoechst 33342, and analyzed and sorted by flow cytometry. Sorted cells were subjected to several tests to determine whether the isolated SP cells displayed features consistent with the stem cell phenotype. Side populations amounting to \u3c1% of total cells, which were sensitive to the ABCG2-inhibitor fumitremorgin C, were found in the conjunctival and limbal epithelia, but were absent from the stem cell-free corneal epithelium. Immunohistochemistry was used to establish the spatial expression pattern of ABCG2. The antigen was detected in clusters of conjunctival and limbal epithelia basal cells but was not present in the corneal epithelium. SP cells were characterized by extremely low light side scattering and contained a high percentage of cells that: showed slow cycling prior to tissue collection; exhibited an initial delay in proliferation after culturing; and displayed clonogenic capacity and resistance to phorbol-induced differentiation; all features that are consistent with a stem cell phenotype
Apoptosis induction by oxidized glycated LDL in human retinal capillary pericytes is independent of activation of MAPK signaling pathways
Survival or death: a dual role of autophagy in stress-induced pericyte loss in diabetic retinopathy
AIMS/HYPOTHESIS: Intra-retinal extravasation and modification of LDL have been implicated in diabetic retinopathy: autophagy may mediate these effects. METHODS: Immunohistochemistry was used to detect autophagy marker LC3B in human and murine diabetic and non-diabetic retinas. Cultured human retinal capillary pericytes (HRCPs) were treated with in vitro-modified heavily-oxidised glycated LDL (HOG-LDL) vs native LDL (N-LDL) with or without autophagy modulators: green fluorescent protein–LC3 transfection; small interfering RNAs against Beclin-1, c-Jun NH(2)-terminal kinase (JNK) and C/EBP-homologous protein (CHOP); autophagy inhibitor 3-MA (5 mmol/l) and/or caspase inhibitor Z-VAD-fmk (100 μmol/l). Autophagy, cell viability, oxidative stress, endoplasmic reticulum stress, JNK activation, apoptosis and CHOP expression were assessed by western blots, CCK-8 assay and TUNEL assay. Finally, HOG-LDL vs N-LDL were injected intravitreally to STZ-induced diabetic vs control rats (yielding 50 and 200 mg protein/l intravitreal concentration) and, after 7 days, retinas were analysed for ER stress, autophagy and apoptosis. RESULTS: Intra-retinal autophagy (LC3B staining) was increased in diabetic vs non-diabetic humans and mice. In HRCPs, 50 mg/l HOG-LDL elicited autophagy without altering cell viability, and inhibition of autophagy decreased survival. At 100–200 mg/l, HOG-LDL caused significant cell death, and inhibition of either autophagy or apoptosis improved survival. Further, 25–200 mg/l HOG-LDL dose-dependently induced oxidative and ER stress. JNK activation was implicated in autophagy but not in apoptosis. In diabetic rat retina, 50 mg/l intravitreal HOG-LDL elicited autophagy and ER stress but not apoptosis; 200 mg/l elicited greater ER stress and apoptosis. CONCLUSIONS: Autophagy has a dual role in diabetic retinopathy: under mild stress (50 mg/l HOG-LDL) it is protective; under more severe stress (200 mg/l HOG-LDL) it promotes cell death. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-016-4058-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users
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