1,583 research outputs found
Withaferin A Suppresses Liver Tumor Growth in a Nude Mouse Model by Downregulation of Cell Signaling Pathway Leading to Invasion and Angiogenesis
Purpose: To investigate the effect of withaferin A on tumor growth and metastasis in liver in a nude mouse model.Methods: Withaferin A was injected through a portal vein to the orthotopic liver tumor in a nude mice model. Xenogen in vivo imaging system was used to monitor tumor growth and metastasis. The effect of withaferin A on tumor volume, invasive growth pattern, expression of Pyk2, upregulation of BAX/P53, apoptotic signaling and ROCK/IP10/VEGF pathway along with cytoskeletal protein actin projection formation was studied. Tumor/non-tumor margin was examined under electron microscopy. In addition, the direct effect of withaferin A on liver cancer cells and endothelial cells was further investigated.Results: A significant inhibition of tumor growth and lower incidence of lung metastasis was observed after withaferin A treatment. Withaferin A treatment led to a decrease in the incidence of intrahepatic metastasis from 90 (9 of 10) to 10 % (1 of 10, p = 0.041). There was decrease in macrophage infiltration in the liver tumors and vessels. Western blot analysis revealed inhibition of expression of Pyk2, ROCK1 protein and VEGF. Electron microscopy showed tumor vascular endothelial cell damage and significant necrosis of tumor tissues. It also suppressed formation of cytoskeletal protein actin projection involved in cell migration.Conclusion: Withaferin A inhibits liver tumor invasion and angiogenesis by downregulation of cell signalling pathway leading to invasion and angiogenesis. Therefore, withaferin A is a promising candidate for the treatment of liver tumor invasion and angiogenesis.Keywords: Withaferin A, Macrophage, Lung metastasis, Angiogenesis, Vascular endothelial growth factor, Rho kinase, Withania somnifer
Full-commanding a network: The dictator
A network of chaotic dynamical systems may synchronize.
For some networks there is the possibility that, coupling a new node to
the network, the synchronization will be commanded by that new node.
That possibility depends on the network and on the way the new node is
coupled to the network.We consider a coupling that can provide what we
call a full-commanding and we define the corresponding full-commandwindow.
The limit situations corresponding to a completely connected
network and to a completely disconnected one provide us some understanding
about what makes a network more receptive or more resistant
to commanding
Cross-domain Transfer Learning and State Inference for Soft Robots via a Semi-supervised Sequential Variational Bayes Framework
Recently, data-driven models such as deep neural networks have shown to be
promising tools for modelling and state inference in soft robots. However,
voluminous amounts of data are necessary for deep models to perform
effectively, which requires exhaustive and quality data collection,
particularly of state labels. Consequently, obtaining labelled state data for
soft robotic systems is challenged for various reasons, including difficulty in
the sensorization of soft robots and the inconvenience of collecting data in
unstructured environments. To address this challenge, in this paper, we propose
a semi-supervised sequential variational Bayes (DSVB) framework for transfer
learning and state inference in soft robots with missing state labels on
certain robot configurations. Considering that soft robots may exhibit distinct
dynamics under different robot configurations, a feature space transfer
strategy is also incorporated to promote the adaptation of latent features
across multiple configurations. Unlike existing transfer learning approaches,
our proposed DSVB employs a recurrent neural network to model the nonlinear
dynamics and temporal coherence in soft robot data. The proposed framework is
validated on multiple setup configurations of a pneumatic-based soft robot
finger. Experimental results on four transfer scenarios demonstrate that DSVB
performs effective transfer learning and accurate state inference amidst
missing state labels. The data and code are available at
https://github.com/shageenderan/DSVB.Comment: Accepted at the International Conference on Robotics and Automation
(ICRA) 202
Anisotropic Structure of the Order Parameter in FeSe0.45Te0.55 Revealed by Angle Resolved Specific Heat
The symmetry and structure of the superconducting gap in the Fe-based
superconductors are the central issue for understanding these novel materials.
So far the experimental data and theoretical models have been highly
controversial. Some experiments favor two or more constant or nearly-constant
gaps, others indicate strong anisotropy and yet others suggest gap zeros
("nodes"). Theoretical models also vary, suggesting that the absence or
presence of the nodes depends quantitatively on the model parameters. An
opinion that has gained substantial currency is that the gap structure, unlike
all other known superconductors, including cuprates, may be different in
different compounds within the same family. A unique method for addressing this
issue, one of the very few methods that are bulk and angle-resolved, calls for
measuring the electronic specific heat in a rotating magnetic field, as a
function of field orientation with respect to the crystallographic axes. In
this Communication we present the first such measurement for an Fe-based
high-Tc superconductor (FeBSC). We observed a fourfold oscillation of the
specific heat as a function of the in-plane magnetic field direction, which
allowed us to identify the locations of the gap minima (or nodes) on the Fermi
surface. Our results are consistent with the expectations of an extended s-wave
model with a significant gap anisotropy on the electron pockets and the gap
minima along the \Gamma M (or Fe-Fe bond) direction.Comment: 32 pages, 7 figure
Integer and half-integer flux-quantum transitions in a niobium/iron-pnictide loop
The recent discovery of iron-based superconductors challenges the existing
paradigm of high-temperature superconductivity. Owing to their unusual
multi-orbital band structure, magnetism, and electron correlation, theories
propose a unique sign reversed s-wave pairing state, with the order parameter
changing sign between the electron and hole Fermi pockets. However, because of
the complex Fermi surface topology and material related issues, the predicted
sign reversal remains unconfirmed. Here we report a novel phase-sensitive
technique for probing unconventional pairing symmetry in the polycrystalline
iron-pnictides. Through the observation of both integer and half-integer
flux-quantum transitions in composite niobium/iron-pnictide loops, we provide
the first phase-sensitive evidence of the sign change of the order parameter in
NdFeAsO0.88F0.12, lending strong support for microscopic models predicting
unconventional s-wave pairing symmetry. These findings have important
implications on the mechanism of pnictide superconductivity, and lay the
groundwork for future studies of new physics arising from the exotic order in
the FeAs-based superconductors.Comment: 23 pages, including 4 figures and supplementary informatio
Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis
© 2016 by the authors; licensee MDPI, Basel, Switzerland.To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.published_or_final_versio
Analyses of Ligand Binding to IP3 Receptors Using Fluorescence Polarization.
Fluorescence polarization (FP) can be used to measure binding of a small fluorescent ligand to a larger protein because the ligand rotates more rapidly in its free form than when bound. When excited with plane polarized light, the free fluorescent ligand emits depolarized light, which can be quantified. Upon binding, its rotation is reduced and more of the emitted light remains polarized. This allows FP to be used as a nondestructive assay of ligand binding. Here we describe a fast, high-throughput FP assay to quantify the binding of fluorescently labeled inositol 1,4,5-trisphosphate (IP3) to N-terminal fragments of the IP3 receptor. The assay is fast (1-6 h), it avoids use of radioactive materials and when measurements are performed at different temperatures, it can resolve Gibbs free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) changes of ligand binding
Transverse electric field–induced deformation of armchair single-walled carbon nanotube
The deformation of armchair single-walled carbon nanotube under transverse electric field has been investigated using density functional theory. The results show that the circular cross-sections of the nanotubes are deformed to elliptic ones, in which the tube diameter along the field direction is increased, whereas the diameter perpendicular to the field direction is reduced. The electronic structures of the deformed nanotubes were also studied. The ratio of the major diameter to the minor diameter of the elliptic cross-section was used to estimate the degree of the deformation. It is found that this ratio depends on the field strength and the tube diameter. However, the field direction has little role in the deformation
Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies
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