935 research outputs found

    Doctors at Risk: A Problem As Viewed by Decision Analysis

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    The authors closely analyze a case in which a Peer Review Organization cited a physician for treatment with potential for significant adverse effect. They also critique the regulatory scheme under which peer review occurs and conclude that such regulation interferes with physicians\u27 primary obligations, fails to encourage cost-effective behavior and may decrease the quality of medical care

    A 3D in vitro model of the human breast duct:A method to unravel myoepithelial-luminal interactions in the progression of breast cancer

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    Abstract Background 3D modelling fulfils a critical role in research, allowing for complex cell behaviour and interactions to be studied in physiomimetic conditions. With tissue banks becoming established for a number of cancers, researchers now have access to primary patient cells, providing the perfect building blocks to recreate and interrogate intricate cellular systems in the laboratory. The ducts of the human breast are composed of an inner layer of luminal cells supported by an outer layer of myoepithelial cells. In early-stage ductal carcinoma in situ, cancerous luminal cells are confined to the ductal space by an intact myoepithelial layer. Understanding the relationship between myoepithelial and luminal cells in the development of cancer is critical for the development of new therapies and prognostic markers. This requires the generation of new models that allows for the manipulation of these two cell types in a physiological setting. Methods Using access to the Breast Cancer Now Tissue Bank, we isolated pure populations of myoepithelial and luminal cells from human reduction mammoplasty specimens and placed them into 2D culture. These cells were infected with lentiviral particles encoding either fluorescent proteins, to facilitate cell tracking, or an inducible human epidermal growth factor receptor 2 (HER2) expression construct. Myoepithelial and luminal cells were then recombined in collagen gels, and the resulting cellular structures were analysed by confocal microscopy. Results Myoepithelial and luminal cells isolated from reduction mammoplasty specimens can be grown separately in 2D culture and retain their differentiated state. When recombined in collagen gels, these cells reform into physiologically reflective bilayer structures. Inducible expression of HER2 in the luminal compartment, once the bilayer has formed, leads to robust luminal filling, recapitulating ductal carcinoma in situ, and can be blocked with anti-HER2 therapies. Conclusions This model allows for the interaction between myoepithelial and luminal cells to be investigated in an in-vitro environment and paves the way to study early events in breast cancer development with the potential to act as a powerful drug discovery platform

    Thrombin A-Chain: Activation Remnant or Allosteric Effector?

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    Although prothrombin is one of the most widely studied enzymes in biology, the role of the thrombin A-chain has been neglected in comparison to the other domains. This paper summarizes the current data on the prothrombin catalytic domain A-chain region and the subsequent thrombin A-chain. Attention is given to biochemical characterization of naturally occurring prothrombin A-chain mutations and alanine scanning mutants in this region. While originally considered to be simply an activation remnant with little physiologic function, the thrombin A-chain is now thought to play a role as an allosteric effector in enzymatic reactions and may also be a structural scaffold to stabilize the protease domain

    Rotating traversable wormholes

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    The general form of a stationary, axially symmetric traversable wormhole is discussed. This provides an explicit class of rotating wormholes that generalize the static, spherically symmetric ones first considered by Morris and Thorne. In agreement with general analyses, it is verified that such a wormhole generically violates the null energy condition at the throat. However, for suitable model wormholes, there can be classes of geodesics falling through it which do not encounter any energy-condition-violating matter. The possible presence of an ergoregion surrounding the throat is also noted.Comment: 15 pages, harvmac; 1 figure in PicTeX; minor changes; to appear in Phys. Rev.

    A chiral crystal in cold QCD matter at intermediate densities?

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    The analogue of Overhauser (particle-hole) pairing in electronic systems (spin-density waves with non-zero total momentum QQ) is analyzed in finite-density QCD for 3 colors and 2 flavors, and compared to the color-superconducting BCS ground state (particle-particle pairing, QQ=0). The calculations are based on effective nonperturbative four-fermion interactions acting in both the scalar diquark as well as the scalar-isoscalar quark-hole ('σ\sigma') channel. Within the Nambu-Gorkov formalism we set up the coupled channel problem including multiple chiral density wave formation, and evaluate the resulting gaps and free energies. Employing medium-modified instanton-induced 't Hooft interactions, as applicable around μq0.4\mu_q\simeq 0.4 GeV (or 4 times nuclear saturation density), we find the 'chiral crystal phase' to be competitive with the color superconductor.Comment: 14 pages ReVTeX, including 11 ps-/eps-figure

    Semiclassical Double-Pomeron Production of Glueballs and η\eta'

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    A semiclassical theory of high energy scattering based on interrupted tunneling (instantons) or QCD sphaleron production has been recently developed to describe the growing hadronic cross section and properties of the soft Pomeron. In this work we address double-pomeron processes in this framework for the first time. We specifically derive the cross section for central production of parity even and odd clusters, scalar and pseudoscalar glueballs, and η\eta' in parton-parton scattering at high energy. We show that the specific dependence of the production cross section on all its kinematical variables compares favorably with the UA8 data on inclusive cluster production, as well as the WA102 data on exclusive central production of scalar glueball and η\eta', in double-pomeron exchange pppp scattering. The magnitude of the cross section and its dependece on kinematic variables is correct, explaining in particular a large deviation from the Pomeron factorization at cluster masses in the range MX<8M_X<8 GeV reported by UA8

    Lidar measurements of ozone and aerosol distributions during the 1992 airborne Arctic stratospheric expedition

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    The NASA Langley airborne differential absorption lidar system was operated from the NASA Ames DC-8 aircraft during the 1992 Airborne Arctic Stratospheric Expedition to investigate the distribution of stratospheric aerosols and ozone (O3) across the Arctic vortex from January to March 1992. Aerosols from the Mt. Pinatubo eruption were found outside and inside the Arctic vortex with distinctly different scattering characteristics and spatial distributions in the two regions. The aerosol and O3 distributions clearly identified the edge of the vortex and provided additional information on vortex dynamics and transport processes. Few polar stratospheric clouds were observed during the AASE-2; however, those that were found had enhanced scattering and depolarization over the background Pinatubo aerosols. The distribution of aerosols inside the vortex exhibited relatively minor changes during the AASE-2. Ozone depletion inside the vortex as limited to less than or equal to 20 percent in the altitude region from 15-20 km

    Biophysical Measurements of Cells, Microtubules, and DNA with an Atomic Force Microscope

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    Atomic force microscopes (AFMs) are ubiquitous in research laboratories and have recently been priced for use in teaching laboratories. Here we review several AFM platforms (Dimension 3000 by Digital Instruments, EasyScan2 by Nanosurf, ezAFM by Nanomagnetics, and TKAFM by Thorlabs) and describe various biophysical experiments that could be done in the teaching laboratory using these instruments. In particular, we focus on experiments that image biological materials and quantify biophysical parameters: 1) imaging cells to determine membrane tension, 2) imaging microtubules to determine their persistence length, 3) imaging the random walk of DNA molecules to determine their contour length, and 4) imaging stretched DNA molecules to measure the tensional force.Comment: 29 page preprint, 7 figures, 1 tabl
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