Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus

BACKGROUND: Worldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARα, β, γ, and RXRα, β, γ) expression is considered to play an important role in development of squamous-cell carcinoma (SCC), which is the most common esophageal cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor levels, have been identified as key risk factors in the development of carcinoma in the aero-digestive tract. Therefore, the aim of the present study was to evaluate protein levels of retinoic acid receptors (i.e. RARα, β, γ, and RXRβ) in esophageal SCC and surrounding normal tissue of patients with untreated SCC and controls. METHODS: All study participants completed a questionnaire concerning smoking and alcohol drinking habits as well as anthropometrical parameters. Protein levels of RARα, β, γ, and RXRβ were determined by Western Blot in normal esophageal tissue and tissue obtained from SCC of 21 patients with newly diagnosed esophageal SCC and normal esophageal tissue of 10 controls. RESULTS: Protein levels of RARγ were significantly lower by ~68% in SCC compared to normal surrounding tissue in patients with SCC that smoked and/or consumed elevated amounts of alcohol. Furthermore, RARα protein levels were significantly lower (~- 45%) in SCC in comparison to normal esophageal mucosa in patients with elevated alcohol intake. When comparing protein levels of retinoic acid receptors between normal tissue of patients with SCC and controls, RARγ protein levels were found to be significantly higher (~2.7-fold) in normal esophageal tissue of SCC patients than in esophageal tissue obtained from controls. No differences were found for RARα, β, and RXRβ protein levels between normal esophageal tissue of patients and that of controls. CONCLUSION: In conclusion, results of the present study suggest that alterations of retinoic acid receptors protein may contribute in the development of SCC in esophagus and that in some patients life style (e.g. smoking and alcohol consumption) may be a critical component in the alteration of retinoic acid receptor levels in esophagus

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

Electrical detection of magnetic skyrmions by non-collinear magnetoresistance

Magnetic skyrmions are localised non-collinear spin textures with high potential for future spintronic applications. Skyrmion phases have been discovered in a number of materials and a focus of current research is the preparation, detection, and manipulation of individual skyrmions for an implementation in devices. Local experimental characterization of skyrmions has been performed by, e.g., Lorentz microscopy or atomic-scale tunnel magnetoresistance measurements using spin-polarised scanning tunneling microscopy. Here, we report on a drastic change of the differential tunnel conductance for magnetic skyrmions arising from their non-collinearity: mixing between the spin channels locally alters the electronic structure, making a skyrmion electronically distinct from its ferromagnetic environment. We propose this non-collinear magnetoresistance (NCMR) as a reliable all-electrical detection scheme for skyrmions with an easy implementation into device architectures

Increased costs reduce reciprocal helping behaviour of humans in a virtual evacuation experiment

Altruistic behaviour is widespread and highly developed in humans and can also be found in some animal species. It has been suggested that altruistic tendencies can depend on costs, benefits and context. Here, we investigate the changes in the occurrence of helping behaviour in a computer-based experiment that simulates an evacuation from a building exploring the effect of varying the cost to help. Our findings illuminate a number of key mechanistic aspects of human decision-making about whether to help or not. In a novel situation where it is difficult to assess the risks associated with higher costs, we reproduce the finding that increasing costs reduce helping and find that the reduction in the frequency of helping behaviour is gradual rather than a sudden transition for a threshold cost level. Interestingly, younger and male participants were more likely to help. We provide potential explanations for this result relating to the nature of our experiment. Finally, we find no evidence that participants in our experiment plan ahead over two consecutive, inter-dependent helping opportunities when conducting cost-benefit trade-offs in spontaneous decisions. We discuss potential applications of our findings to research into decision-making during evacuations

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

Limits on additional planetary companions to OGLE-2005-BLG-390L

We investigate constraints on additional planets orbiting the distant M-dwarf star OGLE-2005-BLG-390L, around which photometric microlensing data has revealed the existence of the sub-Neptune-mass planet OGLE-2005-BLG-390Lb. We specifically aim to study potential Jovian companions and compare our findings with predictions from core-accretion and disc-instability models of planet formation. We also obtain an estimate of the detection probability for sub-Neptune mass planets similar to OGLE-2005-BLG-390Lb using a simplified simulation of a microlensing experiment. We compute the efficiency of our photometric data for detecting additional planets around OGLE-2005-BLG-390L, as a function of the microlensing model parameters and convert it into a function of the orbital axis and planet mass by means of an adopted model of the Milky Way. We find that more than 50 % of potential planets with a mass in excess of 1 M_J between 1.1 and 2.3 AU around OGLE-2005-BLG-390L would have revealed their existence, whereas for gas giants above 3 M_J in orbits between 1.5 and 2.2 AU, the detection efficiency reaches 70 %; however, no such companion was observed. Our photometric microlensing data therefore do not contradict the existence of gas giant planets at any separation orbiting OGLE-2005-BLG-390L. Furthermore we find a detection probability for an OGLE-2005-BLG-390Lb-like planet of around 2-5 %. In agreement with current planet formation theories, this quantitatively supports the prediction that sub-Neptune mass planets are common around low-mass stars.Comment: 10 pages, 4 figures, accepted by A&

A systematic fitting scheme for caustic-crossing microlensing events

We outline a method for fitting binary-lens caustic-crossing microlensing events based on the alternative model parameterisation proposed and detailed in Cassan (2008). As an illustration of our methodology, we present an analysis of OGLE-2007-BLG-472, a double-peaked Galactic microlensing event with a source crossing the whole caustic structure in less than three days. In order to identify all possible models we conduct an extensive search of the parameter space, followed by a refinement of the parameters with a Markov Chain-Monte Carlo algorithm. We find a number of low-chi2 regions in the parameter space, which lead to several distinct competitive best models. We examine the parameters for each of them, and estimate their physical properties. We find that our fitting strategy locates several minima that are difficult to find with other modelling strategies and is therefore a more appropriate method to fit this type of events.Comment: 12 pages, 11 figure

OGLE-2005-BLG-018: Characterization of Full Physical and Orbital Parameters of a Gravitational Binary Lens

We present the analysis result of a gravitational binary-lensing event OGLE-2005-BLG-018. The light curve of the event is characterized by 2 adjacent strong features and a single weak feature separated from the strong features. The light curve exhibits noticeable deviations from the best-fit model based on standard binary parameters. To explain the deviation, we test models including various higher-order effects of the motions of the observer, source, and lens. From this, we find that it is necessary to account for the orbital motion of the lens in describing the light curve. From modeling of the light curve considering the parallax effect and Keplerian orbital motion, we are able to measure not only the physical parameters but also a complete orbital solution of the lens system. It is found that the event was produced by a binary lens located in the Galactic bulge with a distance $6.7\pm 0.3$ kpc from the Earth. The individual lens components with masses $0.9\pm 0.3\ M_\odot$ and $0.5\pm 0.1\ M_\odot$ are separated with a semi-major axis of $a=2.5 \pm 1.0$ AU and orbiting each other with a period $P=3.1 \pm 1.3$ yr. The event demonstrates that it is possible to extract detailed information about binary lens systems from well-resolved lensing light curves.Comment: 19 pages, 6 figure

Emergent Phenomena Induced by Spin-Orbit Coupling at Surfaces and Interfaces

Spin-orbit coupling (SOC) describes the relativistic interaction between the spin and momentum degrees of freedom of electrons, and is central to the rich phenomena observed in condensed matter systems. In recent years, new phases of matter have emerged from the interplay between SOC and low dimensionality, such as chiral spin textures and spin-polarized surface and interface states. These low-dimensional SOC-based realizations are typically robust and can be exploited at room temperature. Here we discuss SOC as a means of producing such fundamentally new physical phenomena in thin films and heterostructures. We put into context the technological promise of these material classes for developing spin-based device applications at room temperature