Quasi-classical Lie algebras and their contractions

After classifying indecomposable quasi-classical Lie algebras in low dimension, and showing the existence of non-reductive stable quasi-classical Lie algebras, we focus on the problem of obtaining sufficient conditions for a quasi-classical Lie algebras to be the contraction of another quasi-classical algebra. It is illustrated how this allows to recover the Yang-Mills equations of a contraction by a limiting process, and how the contractions of an algebra may generate a parameterized families of Lagrangians for pairwise non-isomorphic Lie algebras.Comment: 17 pages, 2 Table

A Unified Approach to Variational Derivatives of Modified Gravitational Actions

Our main aim in this paper is to promote the coframe variational method as a unified approach to derive field equations for any given gravitational action containing the algebraic functions of the scalars constructed from the Riemann curvature tensor and its contractions. We are able to derive a master equation which expresses the variational derivatives of the generalized gravitational actions in terms of the variational derivatives of its constituent curvature scalars. Using the Lagrange multiplier method relative to an orthonormal coframe, we investigate the variational procedures for modified gravitational Lagrangian densities in spacetime dimensions $n\geqslant 3$. We study well-known gravitational actions such as those involving the Gauss-Bonnet and Ricci-squared, Kretchmann scalar, Weyl-squared terms and their algebraic generalizations similar to generic $f(R)$ theories and the algebraic generalization of sixth order gravitational Lagrangians. We put forth a new model involving the gravitational Chern-Simons term and also give three dimensional New massive gravity equations in a new form in terms of the Cotton 2-form

Inflation and Transition to a Slowly Accelerating Phase from S.S.B. of Scale Invariance

We consider the effects of adding a scale invariant $R^{2}$ term to the action of the scale invariant model (SIM) studied previously by one of us (E.I.G., Mod. Phys. Lett. A14, 1043 (1999)). The SIM belongs to the general class of theories, where an integration measure independent of the metric is introduced. To implement scale invariance (S.I.), a dilaton field is introduced. The integration of the equations of motion associated with the new measure gives rise to the spontaneous symmetry breaking (S.S.B) of S.I.. After S.S.B. of S.I. in the model with the $R^{2}$ term, it is found that a non trivial potential for the dilaton is generated. This potential contains two flat regions: one associated with the Planck scale and with an inflationary phase, while the other flat region is associated to a very small vacuum energy (V.E.) and is associated to the present slowly accelerated phase of the universe (S.A.PH). The smallness of the V.E. in the S.A.PH. is understood through the see saw mechanism introduced in S.I.M.Comment: 22 pages, latex, three figures now in separate file

Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted in chromosome ten (PTEN), angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx.</p> <p>Methods</p> <p>We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD) in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored.</p> <p>Results</p> <p>The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively). While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128), there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006) and lymph node metastasis (p = 0.048) but not cartilage invasion (p = 0.129). MVD was significantly higher in high-grade tumors (p = 0.003) but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204). There was also no significant relationship between PTEN and VEGF expression (p = 0.161) and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively).</p> <p>Conclusions</p> <p>Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.</p

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

This is the author accepted manuscript.OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.German Research CouncilAustrian Science FundFaculty of Medicine, Saarland UniversityResearch Council of LithuaniaSwedish Research CouncilMedical Research Counci

N-(4-iodophenyl)-N′-(2-chloroethyl)urea as a microtubule disrupter: in vitro and in vivo profiling of antitumoral activity on CT-26 murine colon carcinoma cell line cultured and grafted to mice

The antitumoral profile of the microtubule disrupter N-(4-iodophenyl)-N′-(2-chloroethyl)urea (ICEU) was characterised in vitro and in vivo using the CT-26 colon carcinoma cell line, on the basis of the drug uptake by the cells, the modifications of cell cycle, and β-tubulin and lipid membrane profiles. N-(4-iodophenyl)-N′-(2-chloroethyl)urea exhibited a rapid and dose-dependent uptake by CT-26 cells suggesting its passive diffusion through the membranes. Intraperitoneally injected ICEU biodistributed into the grafted CT-26 tumour, resulting thus in a significant tumour growth inhibition (TGI). N-(4-iodophenyl)-N′-(2-chloroethyl)urea was also observed to accumulate within colon tissue. Tumour growth inhibition was associated with a slight increase in the number of G2 tetraploid tumour cells in vivo, whereas G2 blockage was more obvious in vitro. The phenotype of β-tubulin alkylation that was clearly demonstrated in vitro was undetectable in vivo. Nuclear magnetic resonance analysis showed that cells blocked in G2 phase underwent apoptosis, as confirmed by an increase in the methylene group resonance of mobile lipids, parallel to sub-G1 accumulation of the cells. In vivo, a decrease of the signals of both the phospholipid precursors and the products of membrane degradation occurred concomitantly with TGI. This multi-analysis established, at least partly, the ICEU activity profile, in vitro and in vivo, providing additional data in favour of ICEU as a tubulin-interacting drug accumulating within the intestinal tract. This may provide a starting point for researches for future efficacious tubulin-interacting drugs for the treatment of colorectal cancers

A Kinematical Approach to Conformal Cosmology

We present an alternative cosmology based on conformal gravity, as originally introduced by H. Weyl and recently revisited by P. Mannheim and D. Kazanas. Unlike past similar attempts our approach is a purely kinematical application of the conformal symmetry to the Universe, through a critical reanalysis of fundamental astrophysical observations, such as the cosmological redshift and others. As a result of this novel approach we obtain a closed-form expression for the cosmic scale factor R(t) and a revised interpretation of the space-time coordinates usually employed in cosmology. New fundamental cosmological parameters are introduced and evaluated. This emerging new cosmology does not seem to possess any of the controversial features of the current standard model, such as the presence of dark matter, dark energy or of a cosmological constant, the existence of the horizon problem or of an inflationary phase. Comparing our results with current conformal cosmologies in the literature, we note that our kinematic cosmology is equivalent to conformal gravity with a cosmological constant at late (or early) cosmological times. The cosmic scale factor and the evolution of the Universe are described in terms of several dimensionless quantities, among which a new cosmological variable delta emerges as a natural cosmic time. The mathematical connections between all these quantities are described in details and a relationship is established with the original kinematic cosmology by L. Infeld and A. Schild. The mathematical foundations of our kinematical conformal cosmology will need to be checked against current astrophysical experimental data, before this new model can become a viable alternative to the standard theory.Comment: Improved version, with minor changes. 58 pages, including 7 figures and one table. Accepted for publication in General Relativity and Gravitation (GERG

The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods

Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes. The EU-ToxRisk project developed a strategy to provide regulatorily valid data, and exemplified this using a panel of > 20 assays (with > 50 individual endpoints), each exposed to 19 well-known test compounds (e.g. rotenone, colchicine, mercury, paracetamol, rifampicine, paraquat, taxol). Examples of strategy implementation are provided for all aspects required to ensure data validity: (i) documentation of test methods in a publicly accessible database; (ii) deposition of standard operating procedures (SOP) at the European Union DB-ALM repository; (iii) test readiness scoring accoding to defined criteria; (iv) disclosure of the pipeline for data processing; (v) link of uncertainty measures and metadata to the data; (vi) definition of test chemicals, their handling and their behavior in test media; (vii) specification of the test purpose and overall evaluation plans. Moreover, data generation was exemplified by providing results from 25 reporter assays. A complete evaluation of the entire test battery will be described elsewhere. A major learning from the retrospective analysis of this large testing project was the need for thorough definitions of the above strategy aspects, ideally in form of a study pre-registration, to allow adequate interpretation of the data and to ensure overall scientific/toxicological validity.Toxicolog