| 2. |
- Abazov, V. M., et al.
(author)
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Jet energy scale determination in the DO experiment
- 2014
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 763, s. 442-475
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Journal article (peer-reviewed)abstract
- The calibration of jet energy measured in the DO detector is presented, based on p (p) over bar collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider, jet energies are measured using a sampling calorimeter composed of uranium and liquid argon as the passive and active media, respectively. This paper describes the energy calibration of jets performed with gamma+jet, Z+jet and dilet events, with jet transverse momentum p(T) > 6 GeV and pseudorapidity range vertical bar eta vertical bar < 3.6, The corrections are measured separately for data and simulation, achieving a precision of 1.4-1.8% for jets in the central part of the calorimeter ancl up to 3.5% for the jets with pseudorapidity vertical bar eta vertical bar = 3.0. Specific corrections are extracted to enhance the description of jet energy in simulation and in particular of the effects due to the flavor of the parton originating the jet, correcting biases up to 3-4% in jets with low PT originating from gluons and up to 6-8% in jets from b quarks. Published by Elsevier B.V.
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| 3. |
- Coelho, Teresa, et al.
(author)
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Safety and efficacy of RNAi therapy for transthyretin amyloidosis
- 2013
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In: The New England journal of medicine. - 1533-4406. ; 369:9, s. 819-29
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Journal article (peer-reviewed)abstract
- BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).
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