Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium ...by Ang2 is believed to potentiate the actions of proangiogenic growth factors. To investigate the specific role of Ang2 in the adult vasculature, we generated a nuclease-resistant RNA aptamer that binds and inhibits Ang2 but not the related Tie2 agonist, angiopoietin-1. Local delivery of this aptamer but not a partially scrambled mutant aptamer inhibited basic fibroblast growth factor-mediated neovascularization in the rat corneal micropocket angiogenesis assay. These in vivo data directly demonstrate that a specific inhibitor of Ang2 can act as an antiangiogenic agent.
Developing aptamers into therapeutics White, R R; Sullenger, B A; Rusconi, C P
The Journal of clinical investigation,
10/2000, Letnik:
106, Številka:
8
Journal Article
The tissue factor/factor VIIa complex is thought to be the primary initiator of most physiologic blood coagulation events. Because of its proximal role in this process, we sought to generate new ...inhibitors of tissue factor/factor VIIa activity by targeting factor VIIa. We employed a combinatorial RNA library and in vitro selection methods to isolate a high affinity, nuclease-resistant RNA ligand that binds specifically to coagulation factor VII/VIIa. This RNA inhibits the tissue factor-dependent activation of factor X by factor VIIa. Kinetic analyses of the mechanism of action of this RNA suggest that it antagonizes factor VIIa activity by preventing formation of a functional factor VII/tissue factor complex. Furthermore, this RNA significantly prolongs the prothrombin time of human plasma in a dose dependent manner, and has an in vitro half-life of approximately 15 h in human plasma. Thus, this RNA ligand represents a novel class of anticoagulant agents directed against factor VIIa.
The Cryogenic Underground Observatory for Rare Events (CUORE) will search for the 0vββ decay in 130Te using a cryogenic array of TeO2 bolometers, operated at a base temperature of ~10mK. CUORE will ...consist of a closely packed array of 19 towers each containing 52 crystals, for a total mass of 741kg. The detector assembly is hosted in one of the largest cryostats ever constructed and will be cooled down to base temperature using a custom-built cryogen free dilution refrigerator. The CUORE cryostat along with the pulse tube based dilution refrigerator has been already commissioned at Laboratori Nazionali del Gran Sasso (LNGS) and a record base temperature, on a cubic meter scale, of ~6mK was achieved during one of the integration runs. We present the results from integration runs, characterizing the system and the cooling performance of the dilution refrigerator, effectively showcasing its stability at base temperature for the expected thermal load.
Luminescent bolometers are double-readout devices able to measure simultaneously the phonon and the light yields after a particle interaction in the detector. This operation allows in some cases to ...tag the type of the interacting quantum, crucial issue for background control in rare event experiments such as the search for neutrinoless double beta decay and for interactions of particle dark matter candidates. The light detectors used in the LUCIFER and LUMINEU searches (projects aiming at the study of the double beta interesting candidates 82Se and 100Mo using ZnSe and ZnMoO4 scintillating bolometers) consist of hyper-pure Ge thin slabs equipped with NTD thermistors. A substantial sensitivity improvement of the Ge light detectors can be obtained applying a proper anti-reflective coatings on the Ge side exposed to the luminescent bolometer. The present paper deals with the investigation of this aspect, proving and quantifying the positive effect of a SiO2 and a SiO coating and setting the experimental bases for future tests of other coating materials. The results confirm that an appropriate coating procedure helps in improving the sensitivity of bolometric light detectors by an important factor (in the range 20% – 35%) and needs to be included in the recipe for the development of an optimized radio-pure scintillating bolometer.
As quantum coherence times of superconducting circuits have increased from nanoseconds to hundreds of microseconds, they are currently one of the leading platforms for quantum information processing. ...However, coherence needs to further improve by orders of magnitude to reduce the prohibitive hardware overhead of current error correction schemes. Reaching this goal hinges on reducing the density of broken Cooper pairs, so-called quasiparticles. Here, we show that environmental radioactivity is a significant source of nonequilibrium quasiparticles. Moreover, ionizing radiation introduces time-correlated quasiparticle bursts in resonators on the same chip, further complicating quantum error correction. Operating in a deep-underground lead-shielded cryostat decreases the quasiparticle burst rate by a factor thirty and reduces dissipation up to a factor four, showcasing the importance of radiation abatement in future solid-state quantum hardware.
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