74 research outputs found
A weakly correlated Fermi liquid state with a small Fermi surface in lightly doped SrIrO
We characterize the electron doping evolution of
(SrLa)IrO by means of angle-resolved photoemission.
Concomitant with the metal insulator transition around we find
the emergence of coherent quasiparticle states forming a closed small Fermi
surface of volume , where is the independently measured La
concentration. The quasiparticle weight remains large along the entire
Fermi surface, consistent with the moderate renormalization of the low-energy
dispersion. This indicates a conventional, weakly correlated Fermi liquid state
with a momentum independent residue in lightly doped
SrIrO$_7&.Comment: 5 pages, 4 figure
A laser-ARPES study of LaNiO3 thin films grown by sputter deposition
Thin films of the correlated transition-metal oxide LaNiO undergo a
metal-insulator transition when their thickness is reduced to a few unit cells.
Here, we use angle-resolved photoemission spectroscopy to study the evolution
of the electronic structure across this transition in a series of epitaxial
LaNiO films of thicknesses ranging from 19 to 2 u.c. grown in situ by RF
magnetron sputtering. Our data show a strong reduction of the electronic mean
free path as the thickness is reduced below 5 u.c. This prevents the system
from becoming electronically two-dimensional, as confirmed by the largely
unchanged Fermi surface seen in our experiments. In the insulating state we
observe a strong suppression of the coherent quasiparticle peak but no clear
gap. These features resemble previous observations of the insulating state of
NdNiO.Comment: Submitted to APL Material
Electronic structure of few-layer black phosphorus from -ARPES
Black phosphorus (BP) stands out among two-dimensional (2D) semiconductors
because of its high mobility and thickness dependent direct band gap. However,
the quasiparticle band structure of ultrathin BP has remained inaccessible to
experiment thus far. Here we use a recently developed laser-based micro-focus
angle resolved photoemission (-ARPES) system to establish the electronic
structure of 2-9 layer BP from experiment. Our measurements unveil ladders of
anisotropic, quantized subbands at energies that deviate from the scaling
observed in conventional semiconductor quantum wells. We quantify the
anisotropy of the effective masses and determine universal tight-binding
parameters which provide an accurate description of the electronic structure
for all thicknesses.Comment: Supporting Information available upon reques
Anomalous quasiparticles in the zone center electron pocket of the kagom\'e ferromagnet Fe3Sn2
One material containing kagome bilayers and featuring both exceptional
magnetism and electron transport is the ferromagnetic metal Fe3Sn2.
Notwithstanding the widespread interest in Fe3Sn2, crystal twinning,
difficulties in distinguishing surface from bulk states, and a large unit cell
have until now prevented the synchrotron-based spectroscopic observation of
sharply resolved quasiparticles near the Fermi surface which could be
responsible for the anomalous properties appearing at low temperatures for the
material. Here we report microfocused laser-based angle-resolved photoemission
spectroscopy (micro-ARPES), which offers the first look at such quasiparticles.
The high spatial resolution allows individual crystal twin domains to be
examined in isolation, resulting in the discovery of three-fold symmetric
electron pockets at the Brillouin zone (BZ) center, not predicted by early
tight-binding descriptions but in agreement with density functional theory
(DFT) calculations, which also feature Weyl nodes. The quasiparticles in these
pockets have remarkably long mean free paths, and their Fermi surface area is
consistent with reported quantum oscillations. At the same time, though, the
best-defined Fermi surface is reduced at low temperature, and the
quasiparticles generally are marginal in the sense that their wavelength
uncertainty is of order the deviation of the quasiparticle wavelength from the
Fermi vector. We attribute these manifestations of strong electron-electron
interactions to a flat band predicted by our DFT to lie just above the
dispersive bands seen in this experiment. Thus, beyond demonstrating the impact
of twin averaging for ARPES measurements of band structures, our experiments
reveal many-body physics unaccounted for by current theories of metallic kagome
ferromagnets
Observation of flat moir\'e bands in twisted bilayer WSe
The recent observation of correlated phases in transition metal
dichalcogenide moir\'e systems at integer and fractional filling promises new
insight into metal-insulator transitions and the unusual states of matter that
can emerge near such transitions. Here, we combine real- and momentum-space
mapping techniques to study moir\'e superlattice effects in 57.4
twisted WSe (tWSe). Our data reveal a split-off flat band that derives
from the monolayer states. Using advanced data analysis, we directly
quantify the moir\'e potential from our data. We further demonstrate that the
global valence band maximum in tWSe is close in energy to this flat band
but derives from the monolayer K-states which show weaker superlattice effects.
These results constrain theoretical models and open the perspective that
-valley flat bands might be involved in the correlated physics of
twisted WSe
Direct evidence for flat bands in twisted bilayer graphene from nano-ARPES
Transport experiments in twisted bilayer graphene revealed multiple
superconducting domes separated by correlated insulating states. These
properties are generally associated with strongly correlated states in a flat
mini-band of the hexagonal moir\'e superlattice as it was predicted by band
structure calculations. Evidence for such a flat band comes from local
tunneling spectroscopy and electronic compressibility measurements, reporting
two or more sharp peaks in the density of states that may be associated with
closely spaced van Hove singularities. Direct momentum resolved measurements
proved difficult though. Here, we combine different imaging techniques and
angle resolved photoemission with simultaneous real and momentum space
resolution (nano-ARPES) to directly map the band dispersion in twisted bilayer
graphene devices near charge neutrality. Our experiments reveal large areas
with homogeneous twist angle that support a flat band with spectral weight that
is highly localized in momentum space. The flat band is separated from the
dispersive Dirac bands which show multiple moir\'e hybridization gaps. These
data establish the salient features of the twisted bilayer graphene band
structure.Comment: Submitted to Nature Materials. Nat. Phys. (2020
Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders
Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26), a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv) antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID) syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action.Conclusions: Although further studies will be necessary to validate the effect of the antibody in vivo, the methodology described here can be extended to select antibodies against hemichannels composed by other connexin isoforms and, consequently, to target other pathologies associated with hyperactive hemichannels. Our study highlights the potential of this approach and identifies connexins as therapeutic targets addressable by screening phage display libraries expressing human randomized antibodies
A Comparative Analysis of Extra-Embryonic Endoderm Cell Lines
Prior to gastrulation in the mouse, all endodermal cells arise from the primitive
endoderm of the blastocyst stage embryo. Primitive endoderm and its derivatives
are generally referred to as extra-embryonic endoderm (ExEn) because the
majority of these cells contribute to extra-embryonic lineages encompassing the
visceral endoderm (VE) and the parietal endoderm (PE). During gastrulation, the
definitive endoderm (DE) forms by ingression of cells from the epiblast. The DE
comprises most of the cells of the gut and its accessory organs. Despite their
different origins and fates, there is a surprising amount of overlap in marker
expression between the ExEn and DE, making it difficult to distinguish between
these cell types by marker analysis. This is significant for two main reasons.
First, because endodermal organs, such as the liver and pancreas, play important
physiological roles in adult animals, much experimental effort has been directed
in recent years toward the establishment of protocols for the efficient
derivation of endodermal cell types in vitro. Conversely,
factors secreted by the VE play pivotal roles that cannot be attributed to the
DE in early axis formation, heart formation and the patterning of the anterior
nervous system. Thus, efforts in both of these areas have been hampered by a
lack of markers that clearly distinguish between ExEn and DE. To further
understand the ExEn we have undertaken a comparative analysis of three ExEn-like
cell lines (END2, PYS2 and XEN). PYS2 cells are derived from embryonal
carcinomas (EC) of 129 strain mice and have been characterized as parietal
endoderm-like [1], END2 cells are derived from P19 ECs and
described as visceral endoderm-like, while XEN cells are derived from blastocyst
stage embryos and are described as primitive endoderm-like. Our analysis
suggests that none of these cell lines represent a bona fide
single in vivo lineage. Both PYS2 and XEN cells represent mixed
populations expressing markers for several ExEn lineages. Conversely END2 cells,
which were previously characterized as VE-like, fail to express many markers
that are widely expressed in the VE, but instead express markers for only a
subset of the VE, the anterior visceral endoderm. In addition END2 cells also
express markers for the PE. We extended these observations with microarray
analysis which was used to probe and refine previously published data sets of
genes proposed to distinguish between DE and VE. Finally, genome-wide pathway
analysis revealed that SMAD-independent TGFbeta signaling through a TAK1/p38/JNK
or TAK1/NLK pathway may represent one mode of intracellular signaling shared by
all three of these lines, and suggests that factors downstream of these pathways
may mediate some functions of the ExEn. These studies represent the first step
in the development of XEN cells as a powerful molecular genetic tool to study
the endodermal signals that mediate the important developmental functions of the
extra-embryonic endoderm. Our data refine our current knowledge of markers that
distinguish various subtypes of endoderm. In addition, pathway analysis suggests
that the ExEn may mediate some of its functions through a non-classical MAP
Kinase signaling pathway downstream of TAK1
Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions
ABSTRACT: The hepatic organic anion transporting poly-peptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug−drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors
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