Identification of methotrexate as a heterochromatin-promoting drug.

Heterochromatin is a tightly packed form of DNA involved in gene silencing, chromosome segregation, and protection of genome stability. Heterochromatin is becoming more recognized in tumor suppression and may thus serve as a potential target for cancer therapy. However, to date there are no drugs that are well established to specifically promote heterochromatin formation. Here, we describe a screening method using Drosophila to identify small molecule compounds that promote heterochromatin formation, with the purpose of developing epigenetic cancer therapeutics. We took advantage of a Drosophila strain with a variegated eye color phenotype that is sensitive to heterochromatin levels, and screened a library of 97 FDA approved oncology drugs. This screen identified methotrexate as the most potent small molecule drug, among the 97 oncology drugs screened, in promoting heterochromatin formation. Interestingly, methotrexate has been identified as a JAK/STAT inhibitor in a functional screen, causing reduced phosphorylation of STAT proteins. These findings are in line with our previous observation that unphosphorylated STAT (uSTAT) promotes heterochromatin formation in both Drosophila and human cells and suppresses tumor growth in mouse xenografts. Thus, Drosophila with variegated eye color phenotypes could be an effective tool for screening heterochromatin-promoting compounds that could be candidates as cancer therapeutics

An hydrodynamic shear instability in stratified disks

We discuss the possibility that astrophysical accretion disks are dynamically unstable to non-axisymmetric disturbances with characteristic scales much smaller than the vertical scale height. The instability is studied using three methods: one based on the energy integral, which allows the determination of a sufficient condition of stability, one using a WKB approach, which allows the determination of the necessary and sufficient condition for instability and a last one by numerical solution. This linear instability occurs in any inviscid stably stratified differential rotating fluid for rigid, stress-free or periodic boundary conditions, provided the angular velocity $\Omega$ decreases outwards with radius $r$. At not too small stratification, its growth rate is a fraction of $\Omega$. The influence of viscous dissipation and thermal diffusivity on the instability is studied numerically, with emphasis on the case when $d \ln \Omega / d \ln r =-3/2$ (Keplerian case). Strong stratification and large diffusivity are found to have a stabilizing effect. The corresponding critical stratification and Reynolds number for the onset of the instability in a typical disk are derived. We propose that the spontaneous generation of these linear modes is the source of turbulence in disks, especially in weakly ionized disks.Comment: 19 pages, 13 figures, to appear in A&

Fermion Pairing Dynamics in the Relativistic Scalar Plasma

Using many-body techniques we obtain the time-dependent Gaussian approximation for interacting fermion-scalar field models. This method is applied to an uniform system of relativistic spin-1/2 fermion field coupled, through a Yukawa term, to a scalar field in 3+1 dimensions, the so-called quantum scalar plasma model. The renormalization for the resulting Gaussian mean-field equations, both static and dynamical, are examined and initial conditions discussed. We also investigate solutions for the gap equation and show that the energy density has a single minimum.Comment: 21 pages, latex, 4 postscript figures, new sections, some literary changes, notation corrections, accepted for publication in Phys. Rev

The non-dipolar magnetic fields of accreting T Tauri stars

Models of magnetospheric accretion on to classical T Tauri stars often assume that stellar magnetic fields are simple dipoles. Recently published surface magnetograms of BP Tau and V2129 Oph have shown, however, that their fields are more complex. The magnetic field of V2129 Oph was found to be predominantly octupolar. For BP Tau the magnetic energy was shared mainly between the dipole and octupole field components, with the dipole component being almost four times as strong as that of V2129 Oph. From the published surface maps of the photospheric magnetic fields we extrapolate the coronal fields of both stars, and compare the resulting field structures with that of a dipole. We consider different models where the disc is truncated at, or well-within, the Keplerian corotation radius. We find that although the structure of the surface magnetic field is particularly complex for both stars, the geometry of the larger scale field, along which accretion is occurring, is somewhat simpler. However, the larger scale field is distorted close to the star by the stronger field regions, with the net effect being that the fractional open flux through the stellar surface is less than would be expected with a dipole magnetic field model. Finally, we estimate the disc truncation radius, assuming that this occurs where the magnetic torque from the stellar magnetosphere is comparable to the viscous torque in the disc.Comment: 14 pages, 8 figures. Figures are reduced resolutio

Spectral method for matching exterior and interior elliptic problems

A spectral method is described for solving coupled elliptic problems on an interior and an exterior domain. The method is formulated and tested on the two-dimensional interior Poisson and exterior Laplace problems, whose solutions and their normal derivatives are required to be continuous across the interface. A complete basis of homogeneous solutions for the interior and exterior regions, corresponding to all possible Dirichlet boundary values at the interface, are calculated in a preprocessing step. This basis is used to construct the influence matrix which serves to transform the coupled boundary conditions into conditions on the interior problem. Chebyshev approximations are used to represent both the interior solutions and the boundary values. A standard Chebyshev spectral method is used to calculate the interior solutions. The exterior harmonic solutions are calculated as the convolution of the free-space Green's function with a surface density; this surface density is itself the solution to an integral equation which has an analytic solution when the boundary values are given as a Chebyshev expansion. Properties of Chebyshev approximations insure that the basis of exterior harmonic functions represents the external near-boundary solutions uniformly. The method is tested by calculating the electrostatic potential resulting from charge distributions in a rectangle. The resulting influence matrix is well-conditioned and solutions converge exponentially as the resolution is increased. The generalization of this approach to three-dimensional problems is discussed, in particular the magnetohydrodynamic equations in a finite cylindrical domain surrounded by a vacuum

X-shooter Observations of the Gravitational Lens System CASSOWARY 5

We confirm an eighth gravitational lens system in the CASSOWARY catalogue. Exploratory observations with the X-shooter spectrograph on the VLT show the system CSWA5 to consist of at least three images of a blue star-forming galaxy at z = 1.0686, lensed by an apparent foreground group of red galaxies one of which is at z = 0.3877. The lensed galaxy exhibits a rich spectrum with broad interstellar absorption lines and a wealth of nebular emission lines. Preliminary analysis of these features shows the galaxy to be young, with an age of 25-50 Myr. With a star-formation rate of approximately 20 solar masses/yr, the galaxy has already assembled a stellar mass of 3 x 10^9 solar masses and reached half-solar metallicity. Its blue spectral energy distribution and Balmer line ratios suggest negligible internal dust extinction. A more in-depth analysis of the properties of this system is currently hampered by the lack of a viable lensing model. However, it is already clear that CSWA5 shares many of its physical characteristics with the general population of UV-selected galaxies at redshifts z = 1-3, motivating further study of both the source and the foreground mass concentration responsible for the gravitational lensing.Comment: 12 pages; Accepted for publication in MNRA

K2: A new method for the detection of galaxy clusters based on CFHTLS multicolor images

We have developed a new method, K2, optimized for the detection of galaxy clusters in multicolor images. Based on the Red Sequence approach, K2 detects clusters using simultaneous enhancements in both colors and position. The detection significance is robustly determined through extensive Monte-Carlo simulations and through comparison with available cluster catalogs based on two different optical methods, and also on X-ray data. K2 also provides quantitative estimates of the candidate clusters' richness and photometric redshifts. Initially K2 was applied to 161 sq deg of two color gri images of the CFHTLS-Wide data. Our simulations show that the false detection rate, at our selected threshold, is only ~1%, and that the cluster catalogs are ~80% complete up to a redshift of 0.6 for Fornax-like and richer clusters and to z ~0.3 for poorer clusters. Based on Terapix T05 release gri photometric catalogs, 35 clusters/sq deg are detected, with 1-2 Fornax-like or richer clusters every two square degrees. Catalogs containing data for 6144 galaxy clusters have been prepared, of which 239 are rich clusters. These clusters, especially the latter, are being searched for gravitational lenses -- one of our chief motivations for cluster detection in CFHTLS. The K2 method can be easily extended to use additional color information and thus improve overall cluster detection to higher redshifts. The complete set of K2 cluster catalogs, along with the supplementary catalogs for the member galaxies, are available on request from the authors.Comment: Accepted in ApJ. 25 pages, including 10 figures. Latex with emulateapj v03/07/0

Theory of commensurable magnetic structures in holmium

The tendency for the period of the helically ordered moments in holmium to lock into values which are commensurable with the lattice is studied theoretically as a function of temperature and magnetic field. The commensurable effects are derived in the mean-field approximation from numerical calculations of the free energy of various commensurable structures, and the results are compared with the extensive experimental evidence collected during the last ten years on the magnetic structures in holmium. In general the stability of the different commensurable structures is found to be in accord with the experiments, except for the tau=5/18 structure observed a few degrees below T_N in a b-axis field. The trigonal coupling recently detected in holmium is found to be the interaction required to explain the increased stability of the tau=1/5 structure around 42 K, and of the tau=1/4 structure around 96 K, when a field is applied along the c-axis.Comment: REVTEX, 31 pages, 7 postscript figure

Luminosity Functions of XMM-LSS C1 Galaxy Clusters

CFHTLS optical photometry has been used to study the galaxy luminosity functions of 14 X-ray selected clusters from the XMM-LSS survey. These are mostly groups and poor clusters, with masses (M_{500}) in the range 0.6 to 19x10 ^{13} M_solar and redshifts 0.05-0.61. Hence these are some of the highest redshift X-ray selected groups to have been studied. Lower and upper colour cuts were used to determine cluster members. We derive individual luminosity functions (LFs) for all clusters as well as redshift-stacked and temperature-stacked LFs in three filters, g', r' and z', down to M=-14.5. All LFs were fitted by Schechter functions which constrained the faint-end slope, alpha, but did not always fit well to the bright end. Derived values of alpha ranged from -1.03 to as steep as -2.1. We find no evidence for upturns at faint magnitudes. Evolution in alpha was apparent in all bands: it becomes shallower with increasing redshift; for example, in the z' band it flattened from -1.75 at low redshift to -1.22 in the redshift range z=0.43-0.61. Eight of our systems lie at z~0.3, and we combine these to generate a galaxy LF in three colours for X-ray selected groups and poor clusters at redshift 0.3. We find that at z~0.3 alpha is steeper (-1.67) in the green (g') band than it is (-1.30) in the red (z') band. This colour trend disappears at low redshift, which we attribute to reddening of faint blue galaxies from z~0.3 to z~0. We also calculated the total optical luminosity and found it to correlate strongly with X-ray luminosity (L_X proportional to L_OPT^(2.1)), and also with ICM temperature (L_OPT proportional to T^(1.62)), consistent with expectations for self-similar clusters with constant mass-to-light ratio. We did not find any convincing correlation of Schechter parameters with mean cluster temperature.Comment: 23 pages, 17 figure