The Effects of Ram-pressure Stripping and Supernova Winds on the Tidal Stirring of Disky Dwarfs: Enhanced Transformation into Dwarf Spheroidals

A conclusive model for the formation of dwarf spheroidal (dSph) galaxies still remains elusive. Owing to their proximity to the massive spirals Milky Way (MW) and M31, various environmental processes have been invoked to explain their origin. In this context, the tidal stirring model postulates that interactions with MW-sized hosts can transform rotationally supported dwarfs, resembling present-day dwarf irregular (dIrr) galaxies, into systems with the kinematic and structural properties of dSphs. Using N-body+SPH simulations, we investigate the dependence of this transformation mechanism on the gas fraction, fgas, in the disk of the progenitor dwarf. Our numerical experiments incorporate for the first time the combined effects of radiative cooling, ram-pressure stripping, star formation, supernova (SN) winds, and a cosmic UV background. For a given orbit inside the primary galaxy, rotationally supported dwarfs with gas fractions akin to those of observed dIrrs (fgas >= 0.5), demonstrate a substantially enhanced likelihood and efficiency of transformation into dSphs relative to their collisionless (fgas = 0) counterparts. We argue that the combination of ram-pressure stripping and SN winds causes the gas-rich dwarfs to respond more impulsively to tides, augmenting their transformation. When fgas >= 0.5, disky dwarfs on previously unfavorable low-eccentricity or large-pericenter orbits are still able to transform. On the widest orbits, the transformation is incomplete; the dwarfs retain significant rotational support, a relatively flat shape, and some gas, naturally resembling transition-type systems. We conclude that tidal stirring constitutes a prevalent evolutionary mechanism for shaping the structure of dwarf galaxies within the currently favored CDM cosmological paradigm.Comment: Accepted for publication in ApJ Letters, 8 pages, 2 figures, LaTeX (uses emulateapj.cls

Observability of Dual Active Galactic Nuclei in Merging Galaxies

Supermassive black holes (SMBHs) have been detected in the centers of most nearby massive galaxies. Galaxies today are the products of billions of years of galaxy mergers, but also billions of years of SMBH activity as active galactic nuclei (AGNs) that is connected to galaxy mergers. In this context, detection of AGN pairs should be relatively common. Observationally, however, dual AGN are scant, being just a few percent of all AGN. In this Letter we investigate the triggering of AGN activity in merging galaxies via a suite of high resolution hydrodynamical simulations. We follow the dynamics and accretion onto the SMBHs as they move from separations of tens of kiloparsecs to tens of parsecs. Our resolution, cooling and star formation implementation produce an inhomogeneous, multi-phase interstellar medium, allowing us to accurately trace star formation and accretion onto the SMBHs. We study the impact of gas content, morphology, and mass ratio, allowing us to study AGN activity and dynamics across a wide range of relevant conditions. We test when the two AGN are simultaneously detectable, for how long and at which separations. We find that strong dual AGN activity occurs during the late phases of the mergers, at small separations (<1-10 kpc) below the resolution limit of most surveys. Much of the SMBH accretion is not simultaneous, limiting the dual AGN fraction detectable through imaging and spectroscopy to a few percent, in agreement with observational samples.Comment: Published in ApJL; additional material available at http://www.astro.lsa.umich.edu/~svanwas/dualAGN.htm

Adaptive Obstacle Avoidance for a Class of Collaborative Robots

In a human–robot collaboration scenario, operator safety is the main problem and must be guaranteed under all conditions. Collision avoidance control techniques are essential to improve operator safety and robot flexibility by preventing impacts that can occur between the robot and humans or with objects inadvertently left within the operational workspace. On this basis, collision avoidance algorithms for moving obstacles are presented in this paper: inspired by algorithms already developed by the authors for planar manipulators, algorithms are adapted for the 6-DOF collaborative manipulators by Universal Robots, and some new contributions are introduced. First, in this work, the safety region wrapping each link of the manipulator assumes a cylindrical shape whose radius varies according to the speed of the colliding obstacle, so that dynamical obstacles are avoided with increased safety regions in order to reduce the risk, whereas fixed obstacles allow us to use smaller safety regions, facilitating the motion of the robot. In addition, three different modalities for the collision avoidance control law are proposed, which differ in the type of motion admitted for the perturbation of the end-effector: the general mode allows for a 6-DOF perturbation, but restrictions can be imposed on the orientation part of the avoidance motion using 4-DOF or 3-DOF modes. In order to demonstrate the effectiveness of the control strategy, simulations with dynamic and fixed obstacles are presented and discussed. Simulations are also used to estimate the required computational effort in order to verify the transferability to a real system

Position Control of a 3-CPU Spherical Parallel Manipulator

The paper presents the first experimental results on the control of a prototypal robot designed for the orientation of parts or tools. The innovative machine is a spherical parallel manipulator actuated by 3 linear motors; several position control schemes have been tested and compared with the final aim of designing an interaction controller. The relative simplicity of machine kinematics allowed to test algorithms requiring the closed-loop evaluation of both inverse and direct kinematics; the compensation of gravitational terms has been experimented as well

miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models

Palbociclib is in early-stage clinical testing in advanced hepatocellular carcinoma (HCC). Here, we investigated whether the anti-tumor activity of palbociclib, which prevents the CDK4/6-mediated phosphorylation of RB1 but simultaneously activates AKT signaling, could be improved by its combination with a PI3K/AKT/mTOR inhibitor in liver cancer models. The selective pan-AKT inhibitor, MK-2206, or the microRNA-199a-3p were tested in combination with palbociclib in HCC cell lines and in the TG221 HCC transgenic mouse model. The combination palbociclib/MK-2206 was highly effective, but too toxic to be tolerated by mice. Conversely, the combination miR-199a-3p mimics/palbociclib not only induced a complete or partial regression of tumor lesions, but was also well tolerated. After 3&nbsp;weeks of treatment, the combination produced a significant reduction in number and size of tumor nodules in comparison with palbociclib or miR-199a-3p mimics used as single agents. Moreover, we also reported the efficacy of this combination against sorafenib-resistant cells in&nbsp;vitro and in&nbsp;vivo. At the molecular level, the combination caused the simultaneous decrease of the phosphorylation of both RB1 and of AKT. Our findings provide pre-clinical evidence for the efficacy of the combination miR-199a-3p/palbociclib as anti-HCC treatment or as a new approach to overcome sorafenib resistance

miR-181b as a therapeutic agent for chronic lymphocytic leukemia in the Eμ-TCL1 mouse model

The involvement of microRNAs (miRNAs) in chronic lymphocytic leukemia (CLL) pathogenesis suggests the possibility of anti-CLL therapeutic approaches based on miRNAs. Here, we used the Eµ-TCL1 transgenic mouse model, which reproduces leukemia with a similar course and distinct immunophenotype as human B-CLL, to test miR-181b as a therapeutic agent.In vitro enforced expression of miR-181b mimics induced significant apoptotic effects in human B-cell lines (RAJI, EHEB), as well as in mouse Eµ-TCL1 leukemic splenocytes. Molecular analyses revealed that miR-181b not only affected the expression of TCL1, Bcl2 and Mcl1 anti-apoptotic proteins, but also reduced the levels of Akt and phospho-Erk1/2. Notably, a siRNA anti-TCL1 could similarly down-modulate TCL1, but exhibited a reduced or absent activity in other relevant proteins, as well as a reduced effect on cell apoptosis and viability. In vivo studies demonstrated the capability of miR-181b to reduce leukemic cell expansion and to increase survival of treated mice.These data indicate that miR-181b exerts a broad range of actions, affecting proliferative, survival and apoptotic pathways, both in mice and human cells, and can potentially be used to reduce expansion of B-CLL leukemic cells

miR-221 affects multiple cancer pathways by modulating the level of hundreds messenger RNAs.

microRNA miR-221 is frequently over-expressed in a variety of human neoplasms. Aim of this study was to identify new miR-221 gene targets to improve our understanding on the molecular tumor-promoting mechanisms affected by miR-221. Gene expression profiling of miR-221-transfected-SNU-398 cells was analyzed by the Sylamer algorithm to verify the enrichment of miR-221 targets among down-modulated genes. This analysis revealed that enforced expression of miR-221 in SNU-398 cells caused the down-regulation of 602 mRNAs carrying sequences homologous to miR-221 seed sequence within their 3'UTRs. Pathways analysis performed on these genes revealed their prominent involvement in cell proliferation and apoptosis. Activation of E2F, MYC, NFkB, and β-catenin pathways was experimentally proven. Some of the new miR-221 target genes, including RB1, WEE1 (cell cycle inhibitors), APAF1 (pro-apoptotic), ANXA1, CTCF (transcriptional repressor), were individually validated as miR-221 targets in SNU-398, HepG2, and HEK293 cell lines. By identifying a large set of miR-221 gene targets, this study improves our knowledge about miR-221 molecular mechanisms involved in tumorigenesis. The modulation of mRNA level of 602 genes confirms the ability of miR-221 to promote cancer by affecting multiple oncogenic pathways

Design of a miniaturized work-cell for micro-manipulation

The paper describes the design and development of a miniaturised workcell devoted to the robotized micro manipulation and assembly of extremely small components, jointly carried out by the University of Brescia, University of Bergamo, University of Ancona and the Institute of Industrial Technologies and Automation of the Italian National Research Council in the framework of the project PRIN2009 MM&A, funded by MIUR. Besides analyzing theoretical and practical aspects related to the design of the work cell components (positioning and orienting devices, grippers, vision and control systems), an automated test bed for the assembly of micro pieces whose typical dimension belongs to the submillimeter scale range has been implemented. The perspective is to contribute to the realization of general automatic production systems at the moment absent for objects of these dimensions