Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling

BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive lipid signaling molecules implicated in tumor dissemination. Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-tethered collagenase thought to be involved in tumor invasion via extracellular matrix degradation. In this study, we investigated the molecular requirements for LPA- and S1P-regulated tumor cell migration in two dimensions (2D) and invasion of three-dimensional (3D) collagen matrices and, in particular, evaluated the role of MT1-MMP in this process. RESULTS: LPA stimulated while S1P inhibited migration of most tumor lines in Boyden chamber assays. Conversely, HT1080 fibrosarcoma cells migrated in response to both lipids. HT1080 cells also markedly invaded 3D collagen matrices (~700 μm over 48 hours) in response to either lipid. siRNA targeting of LPA(1 )and Rac1, or S1P(1), Rac1, and Cdc42 specifically inhibited LPA- or S1P-induced HT1080 invasion, respectively. Analysis of LPA-induced HT1080 motility on 2D substrates vs. 3D matrices revealed that synthetic MMP inhibitors markedly reduced the distance (~125 μm vs. ~45 μm) and velocity of invasion (~0.09 μm/min vs. ~0.03 μm/min) only when cells navigated 3D matrices signifying a role for MMPs exclusively in invasion. Additionally, tissue inhibitors of metalloproteinases (TIMPs)-2, -3, and -4, but not TIMP-1, blocked lipid agonist-induced invasion indicating a role for membrane-type (MT)-MMPs. Furthermore, MT1-MMP expression in several tumor lines directly correlated with LPA-induced invasion. HEK293s, which neither express MT1-MMP nor invade in the presence of LPA, were transfected with MT1-MMP cDNA, and subsequently invaded in response to LPA. When HT1080 cells were seeded on top of or within collagen matrices, siRNA targeting of MT1-MMP, but not other MMPs, inhibited lipid agonist-induced invasion establishing a requisite role for MT1-MMP in this process. CONCLUSION: LPA is a fundamental regulator of MT1-MMP-dependent tumor cell invasion of 3D collagen matrices. In contrast, S1P appears to act as an inhibitory stimulus in most cases, while stimulating only select tumor lines. MT1-MMP is required only when tumor cells navigate 3D barriers and not when cells migrate on 2D substrata. We demonstrate that tumor cells require coordinate regulation of LPA/S1P receptors and Rho GTPases to migrate, and additionally, require MT1-MMP in order to invade collagen matrices during neoplastic progression

Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore

10.1186/1471-2407-13-389BMC Cancer13-BCMA

Noncommutative field gas driven inflation

We investigate early time inflationary scenarios in an Universe filled with a dilute noncommutative bosonic gas at high temperature. A noncommutative bosonic gas is a gas composed of bosonic scalar field with noncommutative field space on a commutative spacetime. Such noncommutative field theories was recently introduced as a generalization of quantum mechanics on a noncommutative spacetime. As key features of these theories are Lorentz invariance violation and CPT violation. In the present study we use a noncommutative bosonic field theory that besides the noncommutative parameter $\theta$ shows up a further parameter $\sigma$. This parameter $\sigma$ controls the range of the noncommutativity and acts as a regulator for the theory. Both parameters play a key role in the modified dispersion relations of the noncommutative bosonic field, leading to possible striking consequences for phenomenology. In this work we obtain an equation of state $p=\omega(\sigma,\theta;\beta)\rho$ for the noncommutative bosonic gas relating pressure $p$ and energy density $\rho$, in the limit of high temperature. We analyse possible behaviours for this gas parameters $\sigma$, $\theta$ and $\beta$, so that $-1\leq\omega<-1/3$, which is the region where the Universe enters an accelerated phase.Comment: Reference added. Version to appear in Journal of Cosmology and Astroparticle Physics - JCA

Hamiltonian submanifolds of regular polytopes

We investigate polyhedral $2k$-manifolds as subcomplexes of the boundary complex of a regular polytope. We call such a subcomplex {\it $k$-Hamiltonian} if it contains the full $k$-skeleton of the polytope. Since the case of the cube is well known and since the case of a simplex was also previously studied (these are so-called {\it super-neighborly triangulations}) we focus on the case of the cross polytope and the sporadic regular 4-polytopes. By our results the existence of 1-Hamiltonian surfaces is now decided for all regular polytopes. Furthermore we investigate 2-Hamiltonian 4-manifolds in the $d$-dimensional cross polytope. These are the "regular cases" satisfying equality in Sparla's inequality. In particular, we present a new example with 16 vertices which is highly symmetric with an automorphism group of order 128. Topologically it is homeomorphic to a connected sum of 7 copies of $S^2 \times S^2$. By this example all regular cases of $n$ vertices with $n < 20$ or, equivalently, all cases of regular $d$-polytopes with $d\leq 9$ are now decided.Comment: 26 pages, 4 figure

Mapping localized surface plasmons within silver nanocubes using cathodoluminescence hyperspectral imaging

Localized surface plasmons within silver nanocubes less than 50 nm in size are investigated using high resolution cathodoluminescence hyperspectral imaging. Multivariate statistical analysis of the multidimensional luminescence dataset allows both the identification of distinct spectral features in the emission and the mapping of their spatial distribution. These results show a 490 nm peak emitted from the cube faces, with shorter wavelength luminescence coming from the vertices and edges; this provides direct experimental confirmation of theoretical predictions

Intelligent Financial Fraud Detection Practices: An Investigation

Financial fraud is an issue with far reaching consequences in the finance industry, government, corporate sectors, and for ordinary consumers. Increasing dependence on new technologies such as cloud and mobile computing in recent years has compounded the problem. Traditional methods of detection involve extensive use of auditing, where a trained individual manually observes reports or transactions in an attempt to discover fraudulent behaviour. This method is not only time consuming, expensive and inaccurate, but in the age of big data it is also impractical. Not surprisingly, financial institutions have turned to automated processes using statistical and computational methods. This paper presents a comprehensive investigation on financial fraud detection practices using such data mining methods, with a particular focus on computational intelligence-based techniques. Classification of the practices based on key aspects such as detection algorithm used, fraud type investigated, and success rate have been covered. Issues and challenges associated with the current practices and potential future direction of research have also been identified.Comment: Proceedings of the 10th International Conference on Security and Privacy in Communication Networks (SecureComm 2014

Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes

This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Environmental Science & Technology, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/es901612v.This study investigated operational factors influencing the removal of steroid estrogens and nonylphenolic compounds in two sewage treatment works, one a nitrifying/denitrifying activated sludge plant and the other a nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal efficiencies of >90% for steroid estrogens and for longer chain nonylphenol ethoxylates (NP4−12EO) were observed at both works, which had equal sludge ages of 13 days. However, the biological activity in terms of milligrams of estrogen removed per day per tonne of biomass was found to be 50−60% more efficient in the nitrifying/denitrifying activated sludge works compared to the works which additionally incorporated phosphorus removal. A temperature reduction of 6 °C had no impact on the removal of free estrogens, but removal of the conjugated estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp) values were greater in the nitrifying/denitrifying works than those in the nitrifying/denitrifying works with phosphorus removal for both steroid estrogens and nonylphenolic compounds possibly indicating a different cell surface structure and therefore microbial population. The difference in biological activity (mg tonne−1 d−1) identified in this study, of up to seven times, suggests that there is the potential for enhancing the removal of estrogens and nonylphenols if more detailed knowledge of the factors responsible for these differences can be identified and maximized, thus potentially improving the quality of receiving waters.Public Utilities Board (Singapore), Anglian Water Ltd, Severn Trent Water Ltd, Thames Water Utilities Ltd, United Utilities 393 Plc and Yorkshire Water Services

Kaluza-Klein Higher Derivative Induced Gravity

The existence and stability analysis of an inflationary solution in a $D+4$-dimensional anisotropic induced gravity is presented in this paper. Nontrivial conditions in the field equations are shown to be compatible with a cosmological model in which the 4-dimension external space evolves inflationary, while, the D-dimension internal one is static. In particular, only two additional constraints on the coupling constants are derived from the abundant field equations and perturbation equations. In addition, a compact formula for the non-redundant 4+D dimensional Friedmann equation is also derived for convenience. Possible implications are also discussed in this paper.Comment: 13 pages, typos/errors corrected, three additional appendices adde

Fermi surface and quasiparticle dynamics of Na(x)CoO2 {x=0.7} investigated by Angle-Resolved Photoemission Spectroscopy

We present an angle-resolved photoemission study of Na0.7CoO2, the host cobaltate of the NaxCoO2.yH2O series. Our results show a large hexagonal-like hole-type Fermi surface, an extremely narrow strongly renormalized quasiparticle band and a small Fermi velocity. Along the Gamma to M high symmetry line, the quasiparticle band crosses the Fermi level from M toward Gamma consistent with a negative sign of effective single-particle hopping (t ): t is estimated to be about 8 meV which is on the order of exchange coupling J in this system. This suggests that t ~ J ~ 10 meV is an important energy scale in the system. Quasiparticles are well defined only in the T-linear resistivity regime. Small single particle hopping and unconventional quasiparticle dynamics may have implications for understanding the unusual behavior of this new class of compounds.Comment: Revised text, Added Figs, Submitted to PR

INTEGRAL and XMM-Newton observations towards the unidentified MeV source GRO J1411-64

The COMPTEL unidentified source GRO J1411-64 was observed by INTEGRAL, and its central part, also by XMM-Newton. The data analysis shows no hint for new detections at hard X-rays. The upper limits in flux herein presented constrain the energy spectrum of whatever was producing GRO J1411-64, imposing, in the framework of earlier COMPTEL observations, the existence of a peak in power output located somewhere between 300-700 keV for the so-called low state. The Circinus Galaxy is the only source detected within the 4$\sigma$ location error of GRO J1411-64, but can be safely excluded as the possible counterpart: the extrapolation of the energy spectrum is well below the one for GRO J1411-64 at MeV energies. 22 significant sources (likelihood $> 10$) were extracted and analyzed from XMM-Newton data. Only one of these sources, XMMU J141255.6-635932, is spectrally compatible with GRO J1411-64 although the fact the soft X-ray observations do not cover the full extent of the COMPTEL source position uncertainty make an association hard to quantify and thus risky. The unique peak of the power output at high energies (hard X-rays and gamma-rays) resembles that found in the SED seen in blazars or microquasars. However, an analysis using a microquasar model consisting on a magnetized conical jet filled with relativistic electrons which radiate through synchrotron and inverse Compton scattering with star, disk, corona and synchrotron photons shows that it is hard to comply with all observational constrains. This and the non-detection at hard X-rays introduce an a-posteriori question mark upon the physical reality of this source, which is discussed in some detail