ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer

Androgen receptor splice variant 7 (AR-V7) is crucial for prostate cancer progression and therapeutic resistance. We show that, independent of ligand, AR-V7 binds both androgen-responsive elements (AREs) and non-canonical sites distinct from full-length AR (AR-FL) targets. Consequently, AR-V7 not only recapitulates AR-FL's partial functions but also regulates an additional gene expression program uniquely via binding to gene promoters rather than ARE enhancers. AR-V7 binding and AR-V7-mediated activation at these unique targets do not require FOXA1 but rely on ZFX and BRD4. Knockdown of ZFX or select unique targets of AR-V7/ZFX, or BRD4 inhibition, suppresses growth of castration-resistant prostate cancer cells. We also define an AR-V7 direct target gene signature that correlates with AR-V7 expression in primary tumors, differentiates metastatic prostate cancer from normal, and predicts poor prognosis. Thus, AR-V7 has both ARE/FOXA1 canonical and ZFX-directed non-canonical regulatory functions in the evolution of anti-androgen therapeutic resistance, providing information to guide effective therapeutic strategies. By cistrome profiling of endogenous androgen receptor (AR) versus an AR splice variant, AR-V7, Cai et al. uncovered non-canonical pathways uniquely targeted by AR-V7 and ZFX, a previously unknown AR-V7 partner. Targeting cofactors (ZFX or BRD4) or non-canonical downstream pathways of AR-V7 provides potential therapeutic ways for treating prostate cancer

Viscous-Inviscid Interactions in a Boundary-Layer Flow Induced by a Vortex Array

In this paper we investigate the asymptotic validity of boundary layer theory. For a flow induced by a periodic row of point-vortices, we compare Prandtl's solution to Navier-Stokes solutions at different $Re$ numbers. We show how Prandtl's solution develops a finite time separation singularity. On the other hand Navier-Stokes solution is characterized by the presence of two kinds of viscous-inviscid interactions between the boundary layer and the outer flow. These interactions can be detected by the analysis of the enstrophy and of the pressure gradient on the wall. Moreover we apply the complex singularity tracking method to Prandtl and Navier-Stokes solutions and analyze the previous interactions from a different perspective

Massive Charged Scalar Quasinormal Modes of Reissner-N\"ordstrom Black Hole Surrounded by Quintessence

We evaluate the complex frequencies of the normal modes for the massive charged scalar field perturbations around a Reissner-N\"ordstrom black hole surrounded by a static and spherically symmetric quintessence using third order WKB approximation approach. Due to the presence of quintessence, quasinormal frequencies damp more slowly. We studied the variation of quasinormal frequencies with charge of the black bole, mass and charge of perturbating scalar field and the quintessential state parameter.Comment: 9 pages, 9 figures and one tabl

Router-level community structure of the Internet Autonomous Systems

The Internet is composed of routing devices connected between them and organized into independent administrative entities: the Autonomous Systems. The existence of different types of Autonomous Systems (like large connectivity providers, Internet Service Providers or universities) together with geographical and economical constraints, turns the Internet into a complex modular and hierarchical network. This organization is reflected in many properties of the Internet topology, like its high degree of clustering and its robustness. In this work, we study the modular structure of the Internet router-level graph in order to assess to what extent the Autonomous Systems satisfy some of the known notions of community structure. We show that the modular structure of the Internet is much richer than what can be captured by the current community detection methods, which are severely affected by resolution limits and by the heterogeneity of the Autonomous Systems. Here we overcome this issue by using a multiresolution detection algorithm combined with a small sample of nodes. We also discuss recent work on community structure in the light of our results

Voyagers 1 and 2 in a Shrunken and Squashed Heliosphere

We have extended our earlier calculations of the distance to the Heliospheric Termination Shock (HTS) - which covered the period from the launch of V1 and V2 in 1977 to 2005 - to the period from 2006 to 2011. During this latter period the solar wind speed, ram pressure and magnetic field decreased to the lowest levels in recent history, related to the sunspot minimum in 2008-2009. The HTS distance has decreased correspondingly so that V1, which was crossed by the HTS at 94 AU in late 2004, would now, in early 2011, be expected to reach the HTS at a distance ~80 AU, when the HTS distance would be expected to be at its minimum. Similarly V2, which was crossed by the HTS at 84 AU in mid 2007, would, in early 2011, reach the HTS at a distance of only 74 AU. These distances, in early 2011, are ~15% less than those at which V1 and V2 initially reached the HTS. The distance to the Heliopause (HP) is more uncertain but recent calculations place its equilibrium distance at between 1.4-1.6 times the HTS distance. Allowing for an additional 1 year for the HP to reach its equilibrium minimum distance relative to the HTS would mean that, assuming this distance remains a constant fraction larger than the HTS distance, the HP distance would be at its minimum distance of (1.4-1.6) x 80 AU = 112-128 AU at V1 in early 2012. At this time V1 will be at a distance of ~120 AU so that there is a possibility that V1 could cross the HP and enter interstellar space at the time 2012.0 \pm 1 year. If the crossing does not happen during this time period, then it is unlikely that V1 will reach this defining boundary before about 2016 because of the expected outward motion of the HTS and the HP towards their more normal distances of 85-96 and ~120 -140 AU coincident with the maximum of the new sunspot cycle.Comment: 23 pages including 7 figure

Enhanced superconductivity in Hf-base metallic glasses

Systematic study of electrical resistivity of Hf_{100-x}Fe_x (x=20,25), Hf_{100-x}Cu_x (x=30,40,50), and Ti_{65}Cu_{35} metallic glasses has been done in the temperature range 0.3 K - 290 K, and in magnetic fields B <= 5 T. All Hf-base alloys are superconducting with T_c >= 0.44 K, which is well above T_c of pure crystalline Hf (0.13 K). From the initial slopes of the upper critical fields, (dH_{c2}/dT)_{T_c}, and resistivities we determined the dressed electronic densities of states, N_{\gamma}(E_F), for all alloys. Both T_c and N_{\gamma}(E_F) decrease with increasing x (Fe and Cu content). The results are compared with those for corresponding Zr-base metallic glasses and ion-implanted Hf films.Comment: 9 pages, 4 figures, 1 tabl

Retained Surgical Items and Minimally Invasive Surgery

A retained surgical item is a surgical patient safety problem. Early reports have focused on the epidemiology of retained-item cases and the identification of patient risk factors for retention. We now know that retention has very little to do with patient characteristics and everything to do with operating room culture. It is a perception that minimally invasive procedures are safer with regard to the risk of retention. Minimally invasive surgery is still an operation where an incision is made and surgical tools are placed inside of patients, so these cases are not immune to the problem of inadvertent retention. Retained surgical items occur because of problems with multi-stakeholder operating room practices and problems in communication. The prevention of retained surgical items will therefore require practice change, knowledge, and shared information between all perioperative personnel