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High glucose-induced Smad3 linker phosphorylation and CCN2 expression are inhibited by dapagliflozin in a diabetic tubule epithelial cell model.
BACKGROUND: In the kidney glucose is freely filtered by the glomerulus and, mainly, reabsorbed by sodium glucose cotransporter 2 (SGLT2) expressed in the early proximal tubule. Human proximal tubule epithelial cells (PTECs) undergo pathological and fibrotic changes seen in diabetic kidney disease (DKD) in response to elevated glucose. We developed a specific in vitro model of DKD using primary human PTECs with exposure to high D-glucose and TGF-β1 and propose a role for SGLT2 inhibition in regulating fibrosis. METHODS: Western blotting was performed to detect cellular and secreted proteins as well as phosphorylated intracellular signalling proteins. qPCR was used to detect CCN2 RNA. Gamma glutamyl transferase (GT) activity staining was performed to confirm PTEC phenotype. SGLT2 and ERK inhibition on high D-glucose, 25 mM, and TGF-β1, 0.75 ng/ml, treated cells was explored using dapagliflozin and U0126, respectively. RESULTS: Only the combination of high D-glucose and TGF-β1 treatment significantly up-regulated CCN2 RNA and protein expression. This increase was significantly ameliorated by dapagliflozin. High D-glucose treatment raised phospho ERK which was also inhibited by dapagliflozin. TGF-β1 increased cellular phospho SSXS Smad3 serine 423 and 425, with and without high D-glucose. Glucose alone had no effect. Smad3 serine 204 phosphorylation was significantly raised by a combination of high D-glucose+TGF-β1; this rise was significantly reduced by both SGLT2 and MEK inhibition. CONCLUSIONS: We show that high D-glucose and TGF-β1 are both required for CCN2 expression. This treatment also caused Smad3 linker region phosphorylation. Both outcomes were inhibited by dapagliflozin. We have identified a novel SGLT2 -ERK mediated promotion of TGF-β1/Smad3 signalling inducing a pro-fibrotic growth factor secretion. Our data evince support for substantial renoprotective benefits of SGLT2 inhibition in the diabetic kidney
Experimental demonstration of a BDCZ quantum repeater node
Quantum communication is a method that offers efficient and secure ways for
the exchange of information in a network. Large-scale quantum communication (of
the order of 100 km) has been achieved; however, serious problems occur beyond
this distance scale, mainly due to inevitable photon loss in the transmission
channel. Quantum communication eventually fails when the probability of a dark
count in the photon detectors becomes comparable to the probability that a
photon is correctly detected. To overcome this problem, Briegel, D\"{u}r, Cirac
and Zoller (BDCZ) introduced the concept of quantum repeaters, combining
entanglement swapping and quantum memory to efficiently extend the achievable
distances. Although entanglement swapping has been experimentally demonstrated,
the implementation of BDCZ quantum repeaters has proved challenging owing to
the difficulty of integrating a quantum memory. Here we realize entanglement
swapping with storage and retrieval of light, a building block of the BDCZ
quantum repeater. We follow a scheme that incorporates the strategy of BDCZ
with atomic quantum memories. Two atomic ensembles, each originally entangled
with a single emitted photon, are projected into an entangled state by
performing a joint Bell state measurement on the two single photons after they
have passed through a 300-m fibre-based communication channel. The entanglement
is stored in the atomic ensembles and later verified by converting the atomic
excitations into photons. Our method is intrinsically phase insensitive and
establishes the essential element needed to realize quantum repeaters with
stationary atomic qubits as quantum memories and flying photonic qubits as
quantum messengers.Comment: 5 pages, 4 figure
Mathematical Modelling of Optical Coherence Tomography
In this chapter a general mathematical model of Optical Coherence Tomography
(OCT) is presented on the basis of the electromagnetic theory. OCT produces
high resolution images of the inner structure of biological tissues. Images are
obtained by measuring the time delay and the intensity of the backscattered
light from the sample considering also the coherence properties of light. The
scattering problem is considered for a weakly scattering medium located far
enough from the detector. The inverse problem is to reconstruct the
susceptibility of the medium given the measurements for different positions of
the mirror. Different approaches are addressed depending on the different
assumptions made about the optical properties of the sample. This procedure is
applied to a full field OCT system and an extension to standard (time and
frequency domain) OCT is briefly presented.Comment: 28 pages, 5 figures, book chapte
An Improved ångström-type model for estimating solar radiation over the tibetan plateau
© 2017 by the authors. For estimating the annual mean of daily solar irradiation in plateau mountainous regions, observed data from 15 radiation stations were used to validate different empirical estimation methods over the Tibetan Plateau. Calibration indicates that sunshine-based site-dependent models perform better than temperature-based ones. Then, the highly rated sunshine-based Ångström model and temperature-based Bristow model were selected for regional application. The geographical models perform much better than the average models, but still not ideally. To achieve better performance, the Ångström-type model was improved using altitude and water vapor pressure as the leading factors. The improved model can accurately predict the coefficients at all the stations, and performs the best among all models with an average Nash-Sutcliffe Efficiency value of 0.856. Spatial distribution of the annual mean of daily solar irradiation was then estimated with the improved model. It is indicated that there is an increasing trend of radiation from east to west, with a great center of the annual mean of daily solar irradiation on southwest Tibetan Plateau ranging from 20 to 24 MJm2. The improved model should be further validated against observations before its applications in other plateau mountainous regions
Phytoestrogens
Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens
Converting Layered Zinc Acetate Nanobelts to One-dimensional Structured ZnO Nanoparticle Aggregates and their Photocatalytic Activity
We were successful in synthesizing periodic layered zinc acetate nanobelts through a hydrothermal solution process. One-dimensional structured ZnO nanoparticle aggregate was obtained by simple thermal annealing of the above-mentioned layered ZnO acetate nanobelts at 300 °C. The morphology, microstructure, and composition of the synthesized ZnO and its precursors were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and infrared spectroscopy, respectively. Low angle X-ray diffraction spectra reveal that as-synthesized zinc acetate has a layered structure with two interlayer d-spacings (one is 1.32 nm and the other is 1.91 nm). SEM and TEM indicate that nanobelt precursors were 100–200 nm in width and possesses length up to 30 μm. Calcination of precursor in air results in the formation of one-dimensional structured ZnO nanoparticle aggregates. In addition, the as-prepared ZnO nanoparticle aggregates exhibit high photocatalytic activity for the photocatalytic degradation of methyl orange (MO)
Nodal quasiparticle meltdown in ultra-high resolution pump-probe angle-resolved photoemission
High- cuprate superconductors are characterized by a strong
momentum-dependent anisotropy between the low energy excitations along the
Brillouin zone diagonal (nodal direction) and those along the Brillouin zone
face (antinodal direction). Most obvious is the d-wave superconducting gap,
with the largest magnitude found in the antinodal direction and no gap in the
nodal direction. Additionally, while antinodal quasiparticle excitations appear
only below , superconductivity is thought to be indifferent to nodal
excitations as they are regarded robust and insensitive to . Here we
reveal an unexpected tie between nodal quasiparticles and superconductivity
using high resolution time- and angle-resolved photoemission on optimally doped
BiSrCaCuO. We observe a suppression of the nodal
quasiparticle spectral weight following pump laser excitation and measure its
recovery dynamics. This suppression is dramatically enhanced in the
superconducting state. These results reduce the nodal-antinodal dichotomy and
challenge the conventional view of nodal excitation neutrality in
superconductivity.Comment: 7 pages, 3 figure. To be published in Nature Physic
A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry
<p>Abstract</p> <p>Background</p> <p>High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate <it>de novo </it>sequencing for identification of post-translational modifications and amino acid polymorphisms.</p> <p>Results</p> <p>In this study, a new <it>de novo </it>sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of <it>Rhodopseudomonas palustris</it>. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of <it>de novo </it>sequenced spectra and the sequencing accuracy.</p> <p>Conclusions</p> <p>Here, we improved <it>de novo </it>sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at <url>http://compbio.ornl.gov/Vonode</url>.</p
Discovery of microscopic electronic inhomogeneity in the high-Tc superconductor Bi2Sr2CaCu2O8+x
The parent compounds of the copper oxide high-Tc superconductors are unusual
insulators. Superconductivity arises when they are properly doped away from
stoichiometry1. In Bi2Sr2CaCu2O8+x, superconductivity results from doping with
excess oxygen atoms, which introduce positive charge carriers (holes) into the
CuO2 planes, where superconductivity is believed to originate. The role of
these oxygen dopants is not well understood, other than the fact that they
provide charge carriers. However, it is not even clear how these charges
distribute in the CuO2 planes. Accordingly, many models of high-Tc
superconductors simply assume that the charge carriers introduced by doping
distribute uniformly, leading to an electronically homogeneous system, as in
ordinary metals. Here we report the observation of an electronic inhomogeneity
in the high-Tc superconductor Bi2Sr2CaCu2O8+x using scanning tunnelling
microscopy/spectroscopy. This inhomogeneity is manifested as spatial variations
in both the local density of states spectrum and the superconducting energy
gap. These variations are correlated spatially and vary on a surprisingly short
length scale of ~ 14 Angs. Analysis suggests that the inhomogeneity observed is
a consequence of proximity to a Mott insulator resulting in poor screening of
the charge potentials associated with the oxygen ions left behind in the BiO
plane after doping. Hence this experiment is a direct probe of the local nature
of the superconducting state, which is not easily accessible by macroscopic
measurements.Comment: 6 pages, 4 figure
Convergence acceleration for multiobjective sparse reconstruction via knowledge transfer
© Springer Nature Switzerland AG 2019. Multiobjective sparse reconstruction (MOSR) methods can potentially obtain superior reconstruction performance. However, they suffer from high computational cost, especially in high-dimensional reconstruction. Furthermore, they are generally implemented independently without reusing prior knowledge from past experiences, leading to unnecessary computational consumption due to the re-exploration of similar search spaces. To address these problems, we propose a sparse-constraint knowledge transfer operator to accelerate the convergence of MOSR solvers by reusing the knowledge from past problem-solving experiences. Firstly, we introduce the deep nonlinear feature coding method to extract the feature mapping between the search of the current problem and a previously solved MOSR problem. Through this mapping, we learn a set of knowledge-induced solutions which contain the search experience of the past problem. Thereafter, we develop and apply a sparse-constraint strategy to refine these learned solutions to guarantee their sparse characteristics. Finally, we inject the refined solutions into the iteration of the current problem to facilitate the convergence. To validate the efficiency of the proposed operator, comprehensive studies on extensive simulated signal reconstruction are conducted
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