102 research outputs found
Bayesian Networks for Max-linear Models
We study Bayesian networks based on max-linear structural equations as
introduced in Gissibl and Kl\"uppelberg [16] and provide a summary of their
independence properties. In particular we emphasize that distributions for such
networks are generally not faithful to the independence model determined by
their associated directed acyclic graph. In addition, we consider some of the
basic issues of estimation and discuss generalized maximum likelihood
estimation of the coefficients, using the concept of a generalized likelihood
ratio for non-dominated families as introduced by Kiefer and Wolfowitz [21].
Finally we argue that the structure of a minimal network asymptotically can be
identified completely from observational data.Comment: 18 page
PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex
“Disclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication inEuropean Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at https://doi.org/10.1530/EJE-17-0227 2017.
The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease
<div><h3>Background</h3><p>Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.</p> <h3>Methodology/Principal Findings</h3><p>OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.</p> <h3>Conclusion/Significance</h3><p>OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.</p> </div
Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer
Osteopontin (OPN), also known as SPP1 (secreted phosphoprotein), is an integrin binding glyco-phosphoprotein produced by a variety of tissues. In cancer patients expression of OPN has been associated with poor prognosis in several tumor types including breast, lung, and colorectal cancers. Despite wide expression in tumor cells and stroma, there is limited evidence supporting role of OPN in tumor progression and metastasis. Using phage display technology we identified a high affinity anti-OPN monoclonal antibody (hereafter AOM1). The binding site for AOM1 was identified as SVVYGLRSKS sequence which is immediately adjacent to the RGD motif and also spans the thrombin cleavage site of the human OPN. AOM1 efficiently inhibited OPNa binding to recombinant integrin αvβ3 with an IC50 of 65 nM. Due to its unique binding site, AOM1 is capable of inhibiting OPN cleavage by thrombin which has been shown to produce an OPN fragment that is biologically more active than the full length OPN. Screening of human cell lines identified tumor cells with increased expression of OPN receptors (αvβ3 and CD44v6) such as mesothelioma, hepatocellular carcinoma, breast, and non-small cell lung adenocarcinoma (NSCLC). CD44v6 and αvβ3 were also found to be highly enriched in the monocyte, but not lymphocyte, subset of human peripheral blood mononuclear cells (hPBMCs). In vitro, OPNa induced migration of both tumor and hPBMCs in a transwell migration assay. AOM1 significantly blocked cell migration further validating its specificity for the ligand. OPN was found to be enriched in mouse plasma in a number of pre-clinical tumor model of non-small cell lung cancers. To assess the role of OPN in tumor growth and metastasis and to evaluate a potential therapeutic indication for AOM1, we employed a KrasG12D-LSLp53fl/fl subcutaneously implanted in vivo model of NSCLC which possesses a high capacity to metastasize into the lung. Our data indicated that treatment of tumor bearing mice with AOM1 as a single agent or in combination with Carboplatin significantly inhibited growth of large metastatic tumors in the lung further supporting a role for OPN in tumor metastasis and progression
Osteopontin deficiency protects against obesity-induced hepatic steatosis and attenuates glucose production in mice
Conservation of energy-momentum of matter as the basis for the gauge theory of gravitation
According to Yang \& Mills (1954), a {\it conserved} current and a related
rigid (`global') symmetry lie at the foundations of gauge theory. When the
rigid symmetry is extended to a {\it local} one, a so-called gauge symmetry, a
new interaction emerges as gauge potential ; its field strength is . In gravity, the conservation of the energy-momentum current of
matter and the rigid translation symmetry in the Minkowski space of special
relativity lie at the foundations of a gravitational gauge theory. If the
translation invariance is made local, a gravitational potential
arises together with its field strength . Thereby
the Minkowski space deforms into a Weitzenb\"ock space with nonvanishing
torsion but vanishing curvature. The corresponding theory is reviewed and
its equivalence to general relativity pointed out. Since translations form a
subgroup of the Poincar\'e group, the group of motion of special relativity,
one ought to straightforwardly extend the gauging of the translations to the
gauging of full Poincar\'e group thereby also including the conservation law of
the {\it angular momentum} current. The emerging Poincar\'e gauge (theory of)
gravity, starting from the viable Einstein-Cartan theory of 1961, will be
shortly reviewed and its prospects for further developments assessed.Comment: 46 pages, 4 figures, minor corrections, references added,
contribution to "One Hundred Years of Gauge Theory" edited by S. De Bianchi
and C. Kiefe
Quantum Spacetime Phenomenology
I review the current status of phenomenological programs inspired by
quantum-spacetime research. I stress in particular the significance of results
establishing that certain data analyses provide sensitivity to effects
introduced genuinely at the Planck scale. And my main focus is on
phenomenological programs that managed to affect the directions taken by
studies of quantum-spacetime theories.Comment: 125 pages, LaTex. This V2 is updated and more detailed than the V1,
particularly for quantum-spacetime phenomenology. The main text of this V2 is
about 25% more than the main text of the V1. Reference list roughly double
Nanotechnology advances towards development of targeted-treatment for obesity
Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modifcation or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specifcity and unsustainable weight loss efects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the
drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side efects, and enhanced efcacy. These efects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbiditie
Comparison of the DeWitt metric in general relativity with the fourth-rank constitutive tensors in electrodynamics and in elasticity theory
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