Biphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents

The clinical use of metallic expandable intravascular stents has resulted in imporved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-biphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine biphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular biphosphonate later on metal alloy surfaces (steel, nitinol, and cobalt-chromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the biphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ration 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P \u3c 0.01). Is is concluded that effective gene vector delivery from metallic stent surfaces can be achieved using this approach

MHD performance demonstration experiment, October 1, 1080-September 30, 1981

The Arnold Engineering Development Center (AEDC) has been under contract with the Department of Energy (DOE) since December 1973 to conduct a magnetohydrodynamic (MHD) High Performance Demonstration Experiment (HPDE). The objective of this experimental research is to demonstrate the attainment of MHD performance on a sufficiently large scale to verify that projected commercial MHD objectives are possible. This report describes the testing of the system under power-producing conditions during the period from October 1, 1980 to September 30, 1981. Experimental results have been obtained with the channel configured in the Faraday mode. Test conditions were selected to produce low supersonic velocity along the entire channel length. Tests have been conducted at magnetic fields up to 4.1 Tesla (T) (70% of design). Up to 30.5 MW of power has been produced to date (60% of design) for an enthalpy extraction of approximately 11%. The high Hall voltage transient, observed during the previous series of tests has been reduced. The reduction is mostly probably due to the fuel and seed being introduced simultaneously. The replacement of the ATJ graphite caps on the electrode walls with pyrolytic graphite caps has resulted in significantly higher surface temperature. As a result, the voltage drop is some 60% of the cold wall voltage drop during the previous series of tests. However, the absolute value of the present voltage drop is still greater than the original design predictions. Test results indicate, however, that the overall enthalpy extraction objective can be achieved

Myrinet: A Gigabit-per-Second Local Area Network

Abstract. Myrinet is a new type of local-area network (LAN) based on the technology used for packet communication and switching within "massivelyparallel processors " (MPPs). Think of Myrinet as an MPP message-passing network that can span campus dimensions, rather than as a wide-area telecommunications network that is operating in close quarters. The technical steps toward making Myrinet a reality included the development of (1) robust, 25m communication channels with flow control, packet framing, and error control; (2) self-initializing, low-latency, cut-through switches; (3) host interfaces that can map the network, select routes, and translate from network addresses to routes, as well as handle packet traffic; and (4) streamlined host software that allows direct communication between user processes and the network. Background. In order to understand how Myrinet differs from conventional LANs such as Ethernet and FDDI, it is helpful to start with Myrinet's genealogy. Myrinet is rooted in the results of two ARPA-sponsored research projects, the Caltech Mosaic, an experimental, fine-grain multicomputer [1], and the USC Information Sciences Institute (USC/ISI) ATOMIC LAN [2, 3], which was built using Mosaic components. Myricom, Inc., is a startup company founded by members of these two research projects. Multicomputer Message-Passing Networks. A multicomputer [4, 5] is an MPP architecture consisting of a collection of computing nodes, each with its own memory, connected by a message-passing network. The Caltech Mosaic was an experiment to "push the envelope " of multicomputer design and programming toward a system with up to tens of thousands of small, single-chip nodes rather than hundreds of circuit-board-size nodes. The fine-grain multicomputer places more extreme demands on the messagepassing network due to the larger number of nodes and a greater interdependence between the computing processes on different nodes. The message-passing-network technology developed for the Mosaic [6] achieved its goals so well that it was used in several other MPP systems, including th