Phase structure and monopoles in U(1) gauge theory

We investigate the phase structure of pure compact U(1) lattice gauge theory in 4 dimensions with the Wilson action supplemented by a monopole term. To overcome the suppression of transitions between the phases in the simulations we make the monopole coupling a dynamical variable. We determine the phase diagram and find that the strength of the first order transition decreases with increasing weight of the monopole term, the transition thus ultimately getting of second order. After outlining the appropriate topological characterization of networks of currents lines, we present an analysis of the occurring monopole currents which shows that the phases are related to topological properties.Comment: 22 pages (latex), 14 figures (available upon request), BU-HEP 94-

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Celecoxib (Celebrex®) was developed as a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of chronic pain. However, it now appears that this compound harbours additional pharmacologic activities that are entirely independent of its COX-2-inhibitory activity. This review presents the recently emerged direct non-COX-2 targets of celecoxib and their proposed role in mediating this drug's antitumour effects

Scaling analysis of the magnetic monopole mass and condensate in the pure U(1) lattice gauge theory

We observe the power law scaling behavior of the monopole mass and condensate in the pure compact U(1) gauge theory with the Villain action. In the Coulomb phase the monopole mass scales with the exponent \nu_m=0.49(4). In the confinement phase the behavior of the monopole condensate is described with remarkable accuracy by the exponent \beta_{exp}=0.197(3). Possible implications of these phenomena for a construction of a strongly coupled continuum U(1) gauge theory are discussed.Comment: Added references [1

Four-dimensional pure compact U(1) gauge theory on a spherical lattice

We investigate the confinement-Coulomb phase transition in the four-dimensional (4D) pure compact U(1) gauge theory on spherical lattices. The action contains the Wilson coupling beta and the double charge coupling gamma. The lattice is obtained from the 4D surface of the 5D cubic lattice by its radial projection onto a 4D sphere, and made homogeneous by means of appropriate weight factors for individual plaquette contributions to the action. On such lattices the two-state signal, impeding the studies of this theory on toroidal lattices, is absent for gamma le 0. Furthermore, here a consistent finite-size scaling behavior of several bulk observables is found, with the correlation length exponent nu in the range nu = 0.35 - 40. These observables include Fisher zeros, specific-heat and cumulant extrema as well as pseudocritical values of beta at fixed gamma. The most reliable determination of nu by means of the Fisher zeros gives nu = 0.365(8). The phase transition at gamma le 0 is thus very probably of 2nd order and belongs to the universality class of a non-Gaussian fixed point.Comment: 40 pages, LaTeX, 12 figure

Renal function during rofecoxib therapy in patients with metastatic cancer: retrospective analysis of a prospective phase II trial

German Clinical Trials Register DRKS: DRKS0000011

Tetanus toxin Hc fragment induces the formation of ceramide platforms and protects neuronal cells against oxidative stress

Tetanus toxin (TeTx) is the protein, synthesized by the anaerobic bacteria Clostridium tetani, which causes tetanus disease. TeTx gains entry into target cells by means of its interaction with lipid rafts, which are membrane domains enriched in sphingomyelin and cholesterol. However, the exact mechanism of host membrane binding remains to be fully established. In the present study we used the recombinant carboxyl terminal fragment from TeTx (Hc-TeTx), the domain responsible for target neuron binding, showing that Hc-TeTx induces a moderate but rapid and sustained increase in the ceramide/sphingomyelin ratio in primary cultures of cerebellar granule neurons and in NGF-differentiated PC12 cells, as well as induces the formation of ceramide platforms in the plasma membrane. The mentioned increase is due to the promotion of neutral sphingomyelinase activity and not to the de novo synthesis, since GW4869, a specific neutral sphingomyelinase inhibitor, prevents neutral sphingomyelinase activity increase and formation of ceramide platforms. Moreover, neutral sphingomyelinase inhibition with GW4869 prevents Hc-TeTx-triggered signaling (Akt phosphorylation), as well as the protective effect of Hc-TeTx on PC12 cells subjected to oxidative stress, while siRNA directed against nSM2 prevents protection by Hc-TeTx of NSC-34 cells against oxidative insult. Finally, neutral sphingomyelinase activity seems not to be related with the internalization of Hc-TeTx into PC12 cells. Thus, the presented data shed light on the mechanisms triggered by TeTx after membrane binding, which could be related with the events leading to the neuroprotective action exerted by the Hc-TeTx fragment

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemoprevention, although the precise molecular mechanisms that link levels of AA, and its metabolites, with cancer progression have still to be elucidated. This article provides an overview of the AA cascade and focuses on the roles of its inhibitors and their implication in cancer treatment. In particular, emphasis is placed on the inhibition of cell proliferation and neo-angiogenesis through inhibition of the enzymes COX-2, 5-LOX and CYP450. Downstream effects of inhibition of AA metabolites are analysed and the molecular mechanisms of action of a selected number of inhibitors of catalytic pathways reviewed. Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention