ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM

The solid tumor microenvironment, pre-metastatic niche, and fibrotic environment are known to have significant biochemical and biomechanical similarities to the fibrotic environment. All have significantly increased levels of factors such as TGFβ, HIF1α, TNFα, PDGF, VEGF, FGF, interleukins and other growth factors that are known to be pro-tumorigenic. Clinical and basic science research has shown that fibrosis presents an environment that favors tumor growth, such as hepatocellular carcinoma being commonly preceded by liver cirrhosis, or bleomycin induced lung fibrosis enhancing pulmonary metastasis in mouse models of breast cancer. In addition to the evidence indicating that fibrosis enhances primary tumor growth and metastasis it is also well characterized that primary tumor metastasis has specific organotropism, for example breast cancer commonly spreads to the lungs, brain, bone, liver and lymph nodes. However, whether non-organtropic fibrosis can redirect metastasis to the damaged organ has not been investigated. To elucidate the fibrotic effect on tumor organotropism we induced fibrosis in the organotropic lungs and in the non-organotropic kidney of two mouse models of breast cancer, the 4T1 murine cancer cell line model and the genetic MMTV-Pymt model, both of which are known to metastasize. Using histopathology, microarrays, gene expression by polymerase chain reaction, ELISA, chemokine array, and in vitro experiments we demonstrate that despite the pro-tumorigenic environment, kidney fibrosis does not redirect metastasis to the non-organotropic damaged organ. However, mice with kidney fibrosis had increased metastasis to their lungs. Furthermore, we found that kidney fibrosis increases the circulating levels of the pro-angiogenic factor Angiopoietin 2 that increased vascular permeability of the lungs, but not the kidneys. In fact, while fibrotic lungs showed decreased expression of endothelial tight gap junction protein Claudin-5, the fibrotic kidneys had an elevated expression of Claudin-5. Our findings suggest that despite the similarities between fibrosis, the tumor microenvironment and the pre-metastatic niche, that while it can enhance tropic metastatic disease, it cannot redirect organotropism indicating that other factors must be involved in directing organotropism. Here we report that tumor organotropism may be a result of organ specific vascular responses to excess circulating factors and increased fibrotic factors. These findings indicate that organotropism is directly related to and as a result of organ specific vascular alterations

Buoyancy Instabilities in Weakly Magnetized Low Collisionality Plasmas

I calculate the linear stability of a stratified low collisionality plasma in the presence of a weak magnetic field. Heat is assumed to flow only along magnetic field lines. In the absence of a heat flux in the background plasma, Balbus (2000) demonstrated that plasmas in which the temperature increases in the direction of gravity are buoyantly unstable to convective-like motions (the ``magnetothermal instability''). I show that in the presence of a background heat flux, an analogous instability is present when the temperature decreases in the direction of gravity. The instability is driven by the background heat flux and the fastest growing mode has a growth time of order the local dynamical time. Thus, independent of the sign of the temperature gradient, weakly magnetized low collisionality plasmas are unstable on a dynamical time to magnetically-mediated buoyancy instabilities. The instability described in this paper is predicted to be present in clusters of galaxies at radii from ~ 0.1-100 kpc, where the observed temperature increases outwards. Possible consequences for the origin of cluster magnetic fields, ``cooling flows,'' and the thermodynamics of the intercluster medium are briefly discussed.Comment: 5 pages; 1 cartoon; ApJ in pres

Beltway: Getting Around Garbage Collection Gridlock

We present the design and implementation of a new garbage collection framework that significantly generalizes existing copying collectors. The Beltway framework exploits and separates object age and incrementality. It groups objects in one or more increments on queues called belts, collects belts independently, and collects increments on a belt in first-in-first-out order. We show that Beltway configurations, selected by command line options, act and perform the same as semi-space, generational, and older-first collectors, and encompass all previous copying collectors of which we are aware. The increasing reliance on garbage collected languages such as Java requires that the collector perform well. We show that the generality of Beltway enables us to design and implement new collectors that are robust to variations in heap size and improve total execution time over the best generational copying collectors of which we are aware by up to 40%, and on average by 5 to 10%, for small to moderate heap sizes. New garbage collection algorithms are rare, and yet we define not just one, but a new family of collectors that subsumes previous work. This generality enables us to explore a larger design space and build better collectors

Hearing the grass grow. Emotional and epistemological challenges of practice-near research

This paper discusses the concept of practice-near research in terms of the emotional and epistemological challenges that arise from the researcher coming 'near' enough to other people for psychological processes to ensue. These may give rise in the researcher to confusion, anxiety and doubt about who is who and what is what; but also to the possibility of real emotional and relational depth in the research process. Using illustrations from three social work doctoral research projects undertaken by students at the Tavistock Clinic and the University of East London the paper examines four themes that seem to the author to be central to meaningful practice-near research undertaken in a spirit of true emotional and epistemological open-mindedness: the smell of the real; losing our minds; the inevitability of personal change; and the discovery of complex particulars

Angular Momentum Transport in Particle and Fluid Disks

We examine the angular momentum transport properties of disks composed of macroscopic particles whose velocity dispersions are externally enhanced (``stirred''). Our simple Boltzmann equation model serves as an analogy for unmagnetized fluid disks in which turbulence may be driven by thermal convection. We show that interparticle collisions in particle disks play the same role as fluctuating pressure forces and viscous dissipation in turbulent disks: both transfer energy in random motions associated with one direction to those associated with another, and convert kinetic energy into heat. The direction of angular momentum transport in stirred particle and fluid disks is determined by the direction of external stirring and by the properties of the collision term in the Boltzmann equation (or its analogue in the fluid problem). In particular, our model problem yields inward transport for vertically or radially stirred disks, provided collisions are suitably inelastic; the transport is outwards in the elastic limit. Numerical simulations of hydrodynamic turbulence driven by thermal convection find inward transport; this requires that fluctuating pressure forces do little to no work, and is analogous to an externally stirred particle disk in which collisions are highly inelastic.Comment: 15 pages; final version accepted by ApJ; minor changes, some clarificatio

MAT for Opioid Use Disorder in Maine

Opioid Use Disorder (OUD) is a major problem in the state of Maine with one person dying from overdose every day. Medication Assisted Treatment (MAT) using Suboxone has been shown to be helpful in the treatment of OUD, but there is currently a great need for providers to prescribe Suboxone in this region. We looked at barriers that providers saw for obtaining a waiver to prescribe Suboxone and created a handout to educate providers on MAT and the process for getting the waiver.https://scholarworks.uvm.edu/fmclerk/1309/thumbnail.jp

The Cocktail Party (January 6-7, 1961)

Program for The Cocktail Party (January 6-7, 1961)