Endometriosis : involvement of stem cells and clinical impact

Introduction: Endometriosis is a common gynaecological disease affecting up to 10% of women of reproductive age. The women suffer from severe abdominal pain and infertility as a consequence of the chronic inflammation. The disease has also been associated with an increased risk of cancer, in particular endometrial and ovarian cancer. Endometriosis represents an important socioeconomic burden as the condition is associated with productivity loss, medical and surgical treatments including assisted reproduction, and a compromised quality of life. The pathophysiology of endometriosis is not fully understood, and as of today we are unable to identify women at risk for cancer development and offer them a tailor-made prophylactic treatment. Aims: The overall aim of this thesis is to explore some of the mechanisms that have an important influence on clinical impact, in particular infertility and the risk of developing endometriosis-associated cancer. The mechanisms enabling endometriotic lesion establishment are explored in an in vitro experimental model and the methylation profile of the fertility-regulating gene HOXA10 is investigated in eutopic and ectopic endometrium. This study also attempts to identify the molecular link between endometriotic stem cells and the development of ovarian cancer by exploring CSC-specific markers and their molecular signatures, and gene expression profile of cancer-correlated molecules in different endometrial compartments. Results: Significant changes were found in the endometrium of women with endometriosis compared to healthy controls. The first study demonstrated the expression of ApoE, ITGB2, ITGB7, LAMC1, CD24, and JAM-1 in women with and without endometriosis. Also, some of the molecules showed a significant altered expression upon comparing endometrium from women with and without endometriosis, as well as eutopic and ectopic endometrium of women with endometriosis. ApoE and JAM-1 were decreased in both proliferative and secretory phase in endometrium from women with endometriosis, and mRNA expression of LAMC1 was reduced in endometrium from endometriosis patients compared with controls in the proliferative phase. CD24 expression was significantly expressed in eutopic and ectopic endometrium in women with endometriosis. In the second study, we found a significant hypermethylation of the HOXA10 gene in eutopic secretory endometrium in women with endometriosis compared with controls. When comparing the methylation profile in patients suffering from ovarian endometriosis with patients presenting extra-ovarian disease, we could not demonstrate any significant correlation between methylation status and stage of disease. The third study demonstrated that mesenchymal endometrial stem cells from women with endometriosis showed an active S-phase as well as an up-regulation of PTEN, VEGF-α, and decreased BCL2 gene-expression compared to controls. A subset of potentially ‘high-risk’ patients could be identified showing a significant up-regulation of genes involved in reprogramming SOX2, NANOG; cancer metabolism TP53, K-ras; and epithelial- mesenchymal transition genes TGF-α and SNAI1. TP53 turned out to play the role of a master regulator. When comparing monolayer to 3D spheroid cultures, an increased coexpression of CSC surface markers CD44 and CD133 was seen, and the chemo-sensitivity assay performed in a 3D-tumour microenvironment revealed increased tumour invasion in the ‘high-risk’ group. In the fourth study, we found a significant difference in the expression of genes that correlated with endometrial malignant transformation in both endometrial stromal and glandular compartments in endometriosis patients compared with controls. Conclusions: Our results shed light on the molecular linkage to the etiology of endometriosis and malignant transformation of endometriosis, as well as providing useful information relevant to endometriosis-associated infertility and pathogenesis

Understanding European Integration with Bipartite Networks of Comparative Advantage

Core objectives of European common market integration are convergence and economic growth, but these are hampered by redundancy, and value chain asymmetries. The challenge is how to harmonize labor division to reach global competitiveness, meanwhile bridging productivity differences across the EU. We develop a bipartite network approach to trace pairwise co-specialization, by applying the Revealed Comparative Advantage method, within and between EU15 and Central and Eastern European (CEE). This approach assesses redundancies and division of labor in the EU at the level of industries and countries. We find significant co-specialization among CEE countries but a diverging specialization between EU15 and CEE. Productivity increases in those CEE industries that have co-specialized with other CEE countries after EU accession, while co-specialization across CEE and EU15 countries is less related to productivity growth. These results show that a division of sectoral specialization can lead to productivity convergence between EU15 and CEE countries.Comment: 17 pages, 4 figures, 6 table

Are rotating strange quark stars good sources of gravitational waves?

We study the viscosity driven (Jacobi-like) bar mode instability of rapidly rotating strange stars in general relativity. A triaxial, "bar shaped" compact star could be an efficient source of continuous wave gravitational radiation in the frequency range of the forthcoming interferometric detectors. We locate the secular instability point along several constant baryon mass sequences of uniformly rotating strange stars described by the MIT bag model. Contrary to neutron stars, strange stars with T/|W| (the ratio of the rotational kinetic energy to the absolute value of the gravitational potential energy) much lower than the corresponding value for the mass-shed limit can be secularly unstable to bar mode formation if shear viscosity is high enough to damp out any deviation from uniform rotation. The instability develops for a broad range of gravitational masses and rotational frequencies of strange quark stars. It imposes strong constraints on the lower limit of the frequency at the innermost stable circular orbit around rapidly rotating strange stars. The above results are robust for all linear self-bound equations of state assuming the growth time of the instability is faster than the damping timescale. We discuss astrophysical scenarios where triaxial instabilities (r-mode and viscosity driven instability) could be relevant in strange stars described by the standard MIT bag model of normal quark matter. Taking into account actual values of viscosities in strange quark matter and neglecting the magnetic field we show that Jacobi-like instability cannot develop in any astrophysicaly interesting temperature windows. The main result is that strange quark stars described by the MIT bag model can be accelerated to very high frequency in Low Mass X-ray binaries if the strange quark mass is ~ 200 MeV or higher.Comment: 15 pages, 10 figures, to appear in Astronomy and Astrophysic

Dynamical charge density fluctuations pervading the phase diagram of a Cu-based high-Tc superconductor

Charge density waves are a common occurrence in all families of high critical temperature superconducting cuprates. Although consistently observed in the underdoped region of the phase diagram and at relatively low temperatures, it is still unclear to what extent they influence the unusual properties of these systems. Using resonant x-ray scattering we carefully determined the temperature dependence of charge density modulations in (Y,Nd)Ba$_2$Cu$_3$O$_{7-{\delta}}$ for three doping levels. We discovered short-range dynamical charge density fluctuations besides the previously known quasi-critical charge density waves. They persist up to well above the pseudogap temperature T*, are characterized by energies of few meV and pervade a large area of the phase diagram, so that they can play a key role in shaping the peculiar normal-state properties of cuprates.Comment: 34 pages, 4 figures, 11 supplementary figure

A simple variance estimator of change for rotating repeated surveys: an application to the EU-SILC household surveys

A common problem is to compare two cross-sectional estimates for the same study variable taken on two different waves or occasions, and to judge whether the change observed is statistically significant. This involves the estimation of the sampling variance of the estimator of change. The estimation of this variance would be relatively straightforward if cross-sectional estimates were based on the same sample. Unfortunately, samples are not completely overlapping, because of rotations used in repeated surveys. We propose a simple approach based on a multivariate (general) linear regression model. The variance estimator proposed is not a model-based estimator. We show that the estimator proposed is design consistent when the sampling fractions are negligible. It can accommodate stratified and two-stage sampling designs. The main advantage of the approach proposed is its simplicity and flexibility. It can be applied to a wide class of sampling designs and can be implemented with standard statistical regression techniques. Because of its flexibility, the approach proposed is well suited for the estimation of variance for the European Union Statistics on Income and Living Conditions surveys. It allows us to use a common approach for variance estimation for the different types of design. The approach proposed is a useful tool, because it involves only modelling skills and requires limited knowledge of survey sampling theory

Hadron attenuation in deep inelastic lepton-nucleus scattering

We present a detailed theoretical investigation of hadron attenuation in deep inelastic scattering (DIS) off complex nuclei in the kinematic regime of the HERMES experiment. The analysis is carried out in the framework of a probabilistic coupled-channel transport model based on the Boltzmann-Uehling-Uhlenbeck (BUU) equation, which allows for a treatment of the final-state interactions (FSI) beyond simple absorption mechanisms. Furthermore, our event-by-event simulations account for the kinematic cuts of the experiments as well as the geometrical acceptance of the detectors. We calculate the multiplicity ratios of charged hadrons for various nuclear targets relative to deuterium as a function of the photon energy nu, the hadron energy fraction z_h=E_h/nu and the transverse momentum p_T. We also confront our model results on double-hadron attenuation with recent experimental data. Separately, we compare the attenuation of identified hadrons (pi^\pm, \pi^0, K^\pm, p and pbar) on Ne and Kr targets with the data from the HERMES Collaboration and make predictions for a Xe target. At the end we turn towards hadron attenuation on Cu nuclei at EMC energies. Our studies demonstrate that (pre-)hadronic final-state interactions play a dominant role in the kinematic regime of the HERMES experiment while our present approach overestimates the attenuation at EMC energies.Comment: 61 pages, 19 figures, version accepted for publication in Phys. Rev.

Efficient red electroluminescence from diketopyrrolopyrrole copolymerised with a polyfluorene

We thank the EC Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 212311 (ONE-P), the RTN THREADMILL (EU-Contract No.: MRTN-CT-2006-036040), the ITNs SUPERIOR (PITN-CT-2009-238177), and CONTEST (PITN-CT-2012-317488) as well as the Royal Society, and EPSRC for funding

The role of motion analysis in elite soccer

The optimal physical preparation of elite soccer (association football) players has become an indispensable part of the professional game especially due to the increased physical demands of match-play. The monitoring of players’ work-rate profiles during competition is now feasible through computer-aided motion analysis. Traditional methods of motion analysis were extremely labour intensive and were largely restricted to university- based research projects. Recent technological developments have meant that sophisticated systems, capable of quickly recording and processing the data of all players’ physical contributions throughout an entire match, are now being used in elite club environments. In recognition of the important role motion analysis now plays as a tool for measuring the physical performance of soccer players, this review critically appraises various motion analysis methods currently employed in elite soccer and explores research conducted using these methods. This review therefore aims to increase the awareness of both practitioners and researchers of the various motion analysis systems available, identify practical implications of the established body of knowledge, while highlighting areas that require further exploration

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio