Mutations and amplification of oncogenes in endometrial cancer

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer

Making waves round a structured cloak: lattices, negative refraction and fringes

Using the framework of transformation optics, this paper presents a detailed analysis of a non-singular square cloak for acoustic, out-of-plane shear elastic and electromagnetic waves. Analysis of wave propagation through the cloak is presented and accompanied by numerical illustrations. The efficacy of the regularized cloak is demonstrated and an objective numerical measure of the quality of the cloaking effect is provided. It is demonstrated that the cloaking effect persists over a wide range of frequencies. As a demonstration of the effectiveness of the regularized cloak, a Young’s double slit experiment is presented. The stability of the interference pattern is examined when a cloaked and uncloaked obstacle are successively placed in front of one of the apertures. This novel link with a well-known quantum mechanical experiment provides an additional method through which the quality of cloaks may be examined. In the second half of the paper, it is shown that an approximate cloak may be constructed using a discrete lattice structure. The efficiency of the approximate lattice cloak is analysed and a series of illustrative simulations presented. It is demonstrated that effective cloaking may be obtained by using a relatively simple lattice structure, particularly, in the low-frequency regime

Analytical Solutions to the Mass-Anisotropy Degeneracy with Higher Order Jeans Analysis: A General Method

The Jeans analysis is often used to infer the total density of a system by relating the velocity moments of an observable tracer population to the underlying gravitational potential. This technique has recently been applied in the search for Dark Matter in objects such as dwarf spheroidal galaxies where the presence of Dark Matter is inferred via stellar velocities. A precise account of the density is needed to constrain the expected gamma ray flux from DM self-annihilation and to distinguish between cold and warm dark matter models. Unfortunately the traditional method of fitting the second order Jeans equation to the tracer dispersion suffers from an unbreakable degeneracy of solutions due to the unknown velocity anisotropy of the projected system. To tackle this degeneracy one can appeal to higher moments of the Jeans equation. By introducing an analog to the Binney anisotropy parameter at fourth order, beta' we create a framework that encompasses all solutions to the fourth order Jeans equations rather than those in the literature that impose unnecessary correlations between anisotropy of second and fourth order moments. The condition beta' = f(beta) ensures that the degeneracy is lifted and we interpret the separable augmented density system as the order-independent case beta'= beta. For a generic choice of beta' we present the line of sight projection of the fourth moment and how it could be incorporated into a joint likelihood analysis of the dispersion and kurtosis. Having presented the mathematical framework, we then use it to develop a statistical method for the purpose of placing constraints on dark matter density parameters from discrete velocity data. The method is tested on simulated dwarf spheroidal data sets leading to results which motivate study of real dwarf spheroidal data sets.Comment: 21 pages, 15 figures. Accepted by MNRAS. Typo corrected in eq. 3

Alfv\'en Reflection and Reverberation in the Solar Atmosphere

Magneto-atmospheres with Alfv\'en speed [a] that increases monotonically with height are often used to model the solar atmosphere, at least out to several solar radii. A common example involves uniform vertical or inclined magnetic field in an isothermal atmosphere, for which the Alfv\'en speed is exponential. We address the issue of internal reflection in such atmospheres, both for time-harmonic and for transient waves. It is found that a mathematical boundary condition may be devised that corresponds to perfect absorption at infinity, and, using this, that many atmospheres where a(x) is analytic and unbounded present no internal reflection of harmonic Alfv\'en waves. However, except for certain special cases, such solutions are accompanied by a wake, which may be thought of as a kind of reflection. For the initial-value problem where a harmonic source is suddenly switched on (and optionally off), there is also an associated transient that normally decays with time as O(t-1) or O(t-1 ln t), depending on the phase of the driver. Unlike the steady-state harmonic solutions, the transient does reflect weakly. Alfv\'en waves in the solar corona driven by a finite-duration train of p-modes are expected to leave such transients.Comment: Accepted by Solar Physic

Astrometry with the Hubble Space Telescope: Trigonometric Parallaxes of Selected Hyads

We present absolute parallaxes and proper motions for seven members of the Hyades open cluster, pre-selected to lie in the core of the cluster. Our data come from archival astrometric data from FGS 3, and newer data for 3 Hyads from FGS 1R, both white-light interferometers on the Hubble Space Telescope (HST). We obtain member parallaxes from six individual Fine Guidance Sensor (FGS) fields and use the field containing van Altena 622 and van Altena 627 (= HIP 21138) as an example. Proper motions, spectral classifications and VJHK photometry of the stars comprising the astrometric refer- ence frames provide spectrophotometric estimates of reference star absolute parallaxes. Introducing these into our model as observations with error, we determine absolute parallaxes for each Hyad. The parallax of vA 627 is significantly improved by including a perturbation orbit for this previously known spectroscopic binary, now an astrometric binary. Compared to our original (1997) determina- tions, a combination of new data, updated calibration, and improved analysis lowered the individual parallax errors by an average factor of 4.5. Comparing parallaxes of the four stars contained in the Hipparcos catalog, we obtain an average factor of 11 times improvement with the HST . With these new results, we also have better agreement with Hipparcos for the four stars in common. These new parallaxes provide an average distance for these seven members, = 47.5 pc, for the core a \pm 1 - {\sigma} dispersion depth of 3.6 pc, and a minimum depth from individual components of 16.0 \pm 0.9 pc. Absolute magnitudes for each member are compared to established main sequences, with excellent agreement. We obtain a weighted average distance modulus for the core of the Hyades of m-M=3.376 \pm 0.01, a value close to the previous Hipparcos values, m-M=3.33\pm 0.02.Comment: 21 pages, 7 figures, Astronomical Journal, accepted 2011-3-

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

The propagation of uncertainties in stellar population synthesis modeling III: model calibration, comparison, and evaluation

Stellar population synthesis (SPS) provides the link between the stellar and dust content of galaxies and their observed spectral energy distributions. In the present work we perform a comprehensive calibration of our own flexible SPS (FSPS) model against a suite of data. Several public SPS models are intercompared, including the models of Bruzual & Charlot (BC03), Maraston (M05) and FSPS. The relative strengths and weaknesses of these models are evaluated, with the following conclusions: 1) The FSPS and BC03 models compare favorably with MC data at all ages, whereas M05 colors are too red and the age-dependence is incorrect; 2) All models yield similar optical and near-IR colors for old metal-poor systems, and yet they all provide poor fits to the integrated J-K and V-K colors of both MW and M31 star clusters; 4) All models predict ugr colors too red, D4000 strengths too strong and Hdelta strengths too weak compared to massive red sequence galaxies, under the assumption that such galaxies are composed solely of old metal-rich stars; 5) FSPS and, to a lesser extent, BC03 can reproduce the optical and near-IR colors of post-starburst galaxies, while M05 cannot. Reasons for these discrepancies are explored. The failure at predicting the ugr colors, D4000, and Hdelta strengths can be explained by some combination of a minority population of metal-poor stars, young stars, blue straggler and/or blue horizontal branch stars, but not by appealing to inadequacies in either theoretical stellar atmospheres or canonical evolutionary phases (e.g., the main sequence turn-off). We emphasize that due to a lack of calibrating star cluster data in regions of the metallicity-age plane relevant for galaxies, all of these models continue to suffer from serious uncertainties that are difficult to quantify. (ABRIDGED)Comment: 26 pages, 16 figures, submitted to ApJ. The FSPS code can be downloaded at http://www.astro.princeton.edu/~cconroy/SPS

The MOND Fundamental Plane

Modified Newtonian Dynamics (MOND) has been shown to be able to fit spiral galaxy rotation curves as well as giving a theoretical foundation for empirically determined scaling relations, such as the Tully - Fisher law, without the need for a dark matter halo. As a complementary analysis, one should investigate whether MOND can also reproduce the dynamics of early - type galaxies (ETGs) without dark matter. As a first step, we here show that MOND can indeed fit the observed central velocity dispersion $\sigma_0$ of a large sample of ETGs assuming a simple MOND interpolating functions and constant anisotropy. We also show that, under some assumptions on the luminosity dependence of the Sersic n parameter and the stellar M/L ratio, MOND predicts a fundamental plane for ETGs : a log - linear relation among the effective radius $R_{eff}$, $\sigma_0$ and the mean effective intensity $\langle I_e \rangle$. However, we predict a tilt between the observed and the MOND fundamental planes.Comment: 16 pages, 2 figures, 2 tables, accepted for publication on MNRA

Role of the Endogenous Antioxidant System in the Protection of Schistosoma mansoni Primary Sporocysts against Exogenous Oxidative Stress

Antioxidants produced by the parasite Schistosoma mansoni are believed to be involved in the maintenance of cellular redox balance, thus contributing to larval survival in their intermediate snail host, Biomphalaria glabrata. Here, we focused on specific antioxidant enzymes, including glutathione-S-transferases 26 and 28 (GST26 and 28), glutathione peroxidase (GPx), peroxiredoxin 1 and 2 (Prx1 and 2) and Cu/Zn superoxide dismutase (SOD), known to be involved in cellular redox reactions, in an attempt to evaluate their endogenous antioxidant function in the early-developing primary sporocyst stage of S. mansoni. Previously we demonstrated a specific and consistent RNA interference (RNAi)-mediated knockdown of GST26 and 28, Prx1 and 2, and GPx transcripts, and an unexpected elevation of SOD transcripts in sporocysts treated with gene-specific double-stranded (ds)RNA. In the present followup study, in vitro transforming sporocysts were exposed to dsRNAs for GST26 and 28, combined Prx1/2, GPx, SOD or green-fluorescent protein (GFP, control) for 7 days in culture, followed by assessment of the effects of specific dsRNA treatments on protein levels using semi-quantitative Western blot analysis (GST26, Prx1/2 only), and larval susceptibility to exogenous oxidative stress in in vitro killing assays. Significant decreases (80% and 50%) in immunoreactive GST26 and Prx1/2, respectively, were observed in sporocysts treated with specific dsRNA, compared to control larvae treated with GFP dsRNA. Sporocysts cultured with dsRNAs for GST26, GST28, Prx1/2 and GPx, but not SOD dsRNA, were significantly increased in their susceptibility to H2O2 oxidative stress (60–80% mortalities at 48 hr) compared to GFP dsRNA controls (∼18% mortality). H2O2-mediated killing was abrogated by bovine catalase, further supporting a protective role for endogenous sporocyst antioxidants. Finally, in vitro killing of S. mansoni sporocysts by hemocytes of susceptible NMRI B. glabrata snails was increased in larvae treated with Prx1/2, GST26 and GST28 dsRNA, compared to those treated with GFP or SOD dsRNAs. Results of these experiments strongly support the hypothesis that endogenous expression and regulation of larval antioxidant enzymes serve a direct role in protection against external oxidative stress, including immune-mediated cytotoxic reactions. Moreover, these findings illustrate the efficacy of a RNAi-type approach in investigating gene function in larval schistosomes