175 research outputs found
MoTe2: A Type-II Weyl Topological Metal
Based on the ab initio calculations, we show that MoTe2, in its
low-temperature orthorhombic structure characterized by an X-ray diffraction
study at 100 K, realizes 4 type-II Weyl points between the N-th and N+1-th
bands, where N is the total number of valence electrons per unit cell. Other
WPs and nodal lines between different other bands also appear close to the
Fermi level due to a complex topological band structure. We predict a series of
strain-driven topological phase transitions in this compound, opening a wide
range of possible experimental realizations of different topological semimetal
phases. Crucially, with no strain, the number of observable surface Fermi arcs
in this material is 2 - the smallest number of arcs consistent with
time-reversal symmetry.Comment: Published versio
Correction of non-linearity effects in detectors for electron spectroscopy
Using photoemission intensities and a detection system employed by many
groups in the electron spectroscopy community as an example, we have
quantitatively characterized and corrected detector non-linearity effects over
the full dynamic range of the system. Non-linearity effects are found to be
important whenever measuring relative peak intensities accurately is important,
even in the low-countrate regime. This includes, for example, performing
quantitative analyses for surface contaminants or sample bulk stoichiometries,
where the peak intensities involved can differ by one or two orders of
magnitude, and thus could occupy a significant portion of the detector dynamic
range. Two successful procedures for correcting non-linearity effects are
presented. The first one yields directly the detector efficiency by measuring a
flat-background reference intensity as a function of incident x-ray flux, while
the second one determines the detector response from a least-squares analysis
of broad-scan survey spectra at different incident x-ray fluxes. Although we
have used one spectrometer and detection system as an example, these
methodologies should be useful for many other cases.Comment: 13 pages, 12 figure
Automated construction of symmetrized Wannier-like tight-binding models from ab initio calculations
Wannier tight-binding models are effective models constructed from
first-principles calculations. As such, they bridge a gap between the accuracy
of first-principles calculations and the computational simplicity of effective
models. In this work, we extend the existing methodology of creating Wannier
tight-binding models from first-principles calculations by introducing the
symmetrization post-processing step, which enables the production of
Wannier-like models that respect the symmetries of the considered crystal.
Furthermore, we implement automatic workflows, which allow for producing a
large number of tight-binding models for large classes of chemically and
structurally similar compounds, or materials subject to external influence such
as strain. As a particular illustration, these workflows are applied to
strained III-V semiconductor materials. These results can be used for further
study of topological phase transitions in III-V quantum wells
Optical tools for visualizing and controlling human GLP-1 receptor activation with high spatiotemporal resolution
The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well as of the blockbuster weight-loss drugs semaglutide and liraglutide. Despite its large clinical relevance, tools to investigate the precise activation dynamics of this receptor with high spatiotemporal resolution are limited. Here we introduce a novel genetically-encoded sensor based on the engineering of a circularly-permuted green fluorescent protein into the human GLP1R, named GLPLight1. We demonstrate that fluorescence signal from GLPLight1 accurately reports the expected receptor conformational activation in response to pharmacological ligands with high sensitivity (max ΔF/F0 = 528%) and temporal resolution (τON = 4.7 sec). We further demonstrated that GLPLight1 shows comparable responses to GLP-1 derivatives as observed for the native receptor. Using GLPLight1, we established an all-optical assay to characterize a novel photocaged GLP-1 derivative (photo-GLP1) and to demonstrate optical control of GLP1R activation. Thus, the new all-optical toolkit introduced here enhances our ability to study GLP1R activation with high spatiotemporal resolution
Dysregulation of the norepinephrine transporter sustains cortical hypodopaminergia and schizophrenia-like behaviors in neuronal rictor null mice
Abstract The mammalian target of rapamycin (mTOR) complex 2 (mTORC2) is a multimeric signaling unit that phosphorylates protein kinase B/Akt following hormonal and growth factor stimulation. Defective Akt phosphorylation at the mTORC2-catalyzed Ser473 site has been linked to schizophrenia. While human imaging and animal studies implicate a fundamental role for Akt signaling in prefrontal dopaminergic networks, the molecular mechanisms linking Akt phosphorylation to specific schizophrenia-related neurotransmission abnormalities have not yet been described. Importantly, current understanding of schizophrenia suggests that cortical decreases in DA neurotransmission and content, defined here as cortical hypodopaminergia, contribute to both the cognitive deficits and the negative symptoms characteristic of this disorder. We sought to identify a mechanism linking aberrant Akt signaling to these hallmarks of schizophrenia. We used conditional gene targeting in mice to eliminate the mTORC2 regulatory protein rictor in neurons, leading to impairments in neuronal Akt Ser473 phosphorylation. Rictor-null (KO) mice exhibit prepulse inhibition (PPI) deficits, a schizophrenia-associated behavior. In addition, they show reduced prefrontal dopamine (DA) content, elevated cortical norepinephrine (NE), unaltered cortical serotonin (5-HT), and enhanced expression of the NE transporter (NET). In the cortex, NET takes up both extracellular NE and DA. Thus, we propose that amplified NET function in rictor KO mice enhances accumulation of both NE and DA within the noradrenergic neuron. This phenomenon leads to conversion of DA to NE and ultimately supports both increased NE tissue content as well as a decrease in DA. In support of this hypothesis, NET blockade in rictor KO mice reversed cortical deficits in DA content and PPI, suggesting that dysregulation of DA homeostasis is driven by alteration in NET expression, which we show is ultimately influenced by Akt phosphorylation status. These data illuminate a molecular link, Akt regulation of NET, between the recognized association of Akt signaling deficits in schizophrenia with a specific mechanism for cortical hypodopaminergia and hypofunction. Additionally, our findings identify Akt as a novel modulator of monoamine homeostasis in the cortex
Automated construction of symmetrized Wannier-like tight-binding models from ab initio calculations
Wannier tight-binding models are effective models constructed from first-principles calculations. As such, they bridge a gap between the accuracy of first-principles calculations and the computational simplicity of effective models. In this work, we extend the existing methodology of creating Wannier tight-binding models from first-principles calculations by introducing the symmetrization post-processing step, which enables the production of Wannier-like models that respect the symmetries of the considered crystal. Furthermore, we implement automatic workflows, which allow for producing a large number of tight-binding models for large classes of chemically and structurally similar compounds or materials subject to external influence such as strain. As a particular illustration, these workflows are applied to strained III-V semiconductor materials. These results can be used for further study of topological phase transitions in III-V quantum wells
Molecular Ultrasound Imaging of Junctional Adhesion Molecule A Depicts Acute Alterations in Blood Flow and Early Endothelial Dysregulation
Objective: The junctional adhesion molecule A (JAM-A) is physiologically located in interendothelial tight junctions and focally redistributes to the luminal surface of blood vessels under abnormal shear and flow conditions accompanying atherosclerotic lesion development. Therefore, JAM-A was evaluated as a target for molecularly targeted ultrasound imaging of transient endothelial dysfunction under acute blood flow variations.
Approach and Results: Flow-dependent endothelial dysfunction was induced in apolipoprotein E-deficient mice (n=43) by carotid partial ligation. JAM-A expression was investigated by molecular ultrasound using antibody-targeted poly(n-butyl cyanoacrylate) microbubbles and validated with immunofluorescence. Flow disturbance and arterial remodeling were assessed using functional ultrasound. Partial ligation led to an immediate drop in perfusion at the ligated side and a direct compensatory increase at the contralateral side. This was accompanied by a strongly increased JAM-A expression and JAM-A-targeted microbubbles binding at the partially ligated side and by a moderate and temporary increase in the contralateral artery (approximate to 14x [P<0.001] and approximate to 5x [P<0.001] higher than control, respectively), both peaking after 2 weeks. Subsequently, although JAM-A expression and JAM-A-targeted microbubbles binding persisted at a higher level at the partially ligated side, it completely normalized within 4 weeks at the contralateral side. Conclusions: Temporary blood flow variations induce endothelial rearrangement of JAM-A, which can be visualized using JAM-A-targeted microbubbles. Thus, JAM-A may be considered as a marker of acute endothelial activation and dysfunction. Its imaging may facilitate the early detection of cardiovascular risk areas, and it enables the therapeutic prevention of their progression toward an irreversible pathological state
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