Implementation of the 64-meter-diameter Antennas at the Deep Space Stations in Australia and Spain

The management and construction aspects of the Overseas 64-m Antenna Project in which two 64-m antennas were constructed at the Tidbinbilla Deep Space Communications Complex in Australia, and at the Madrid Deep Space Communications Complex in Spain are described. With the completion of these antennas the Deep Space Network is equipped with three 64-m antennas spaced around the world to maintain continuous coverage of spacecraft operations. These antennas provide approximately a 7-db gain over the capabilities of the existing 26-m antenna nets. The report outlines the project organization and management, resource utilization, fabrication, quality assurance, and construction methods by which the project was successfully completed. Major problems and their solutions are described as well as recommendations for future projects

Demonstration of the Zero-Crossing Phasemeter with a LISA Test-bed Interferometer

The Laser Interferometer Space Antenna (LISA) is being designed to detect and study in detail gravitational waves from sources throughout the Universe such as massive black hole binaries. The conceptual formulation of the LISA space-borne gravitational wave detector is now well developed. The interferometric measurements between the sciencecraft remain one of the most important technological and scientific design areas for the mission. Our work has concentrated on developing the interferometric technologies to create a LISA-like optical signal and to measure the phase of that signal using commercially available instruments. One of the most important goals of this research is to demonstrate the LISA phase timing and phase reconstruction for a LISA-like fringe signal, in the case of a high fringe rate and a low signal level. We present current results of a test-bed interferometer designed to produce an optical LISA-like fringe signal previously discussed in the literature.Comment: find minor corrections in the CQG versio

Optimizing the Earth-LISA "rendez-vous"

We present a general survey of heliocentric LISA orbits, hoping it might help in the exercise of rescoping the mission. We try to semi-analytically optimize the orbital parameters in order to minimize the disturbances coming from the Earth-LISA interaction. In a set of numerical simulations we include nonautonomous perturbations and provide an estimate of Doppler shift and breathing as a function of the trailing angle.Comment: 18 pages, 16 figures. Submitted on CQ

Effects of Interplanetary Dust on the LISA drag-free Constellation

The analysis of non-radiative sources of static or time-dependent gravitational fields in the Solar System is crucial to accurately estimate the free-fall orbits of the LISA space mission. In particular, we take into account the gravitational effects of Interplanetary Dust (ID) on the spacecraft trajectories. The perturbing gravitational field has been calculated for some ID density distributions that fit the observed zodiacal light. Then we integrated the Gauss planetary equations to get the deviations from the LISA keplerian orbits around the Sun. This analysis can be eventually extended to Local Dark Matter (LDM), as gravitational fields are expected to be similar for ID and LDM distributions. Under some strong assumptions on the displacement noise at very low frequency, the Doppler data collected during the whole LISA mission could provide upper limits on ID and LDM densities.Comment: 11 pages, 6 figures, to be published on the special issue of "Celestial Mechanics and Dynamical Astronomy" on the CELMEC V conferenc

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of \u3cem\u3eFARS2\u3c/em\u3e-linked Disease

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins

Coherent interaction of laser pulses in a resonant optically dense extended medium under the regime of strong field-matter coupling

Nonstationary pump-probe interaction between short laser pulses propagating in a resonant optically dense coherent medium is considered. A special attention is paid to the case, where the density of two-level particles is high enough that a considerable part of the energy of relatively weak external laser-fields can be coherently absorbed and reemitted by the medium. Thus, the field of medium reaction plays a key role in the interaction processes, which leads to the collective behavior of an atomic ensemble in the strongly coupled light-matter system. Such behavior results in the fast excitation interchanges between the field and a medium in the form of the optical ringing, which is analogous to polariton beating in the solid-state optics. This collective oscillating response, which can be treated as successive beats between light wave-packets of different group velocities, is shown to significantly affect propagation and amplification of the probe field under its nonlinear interaction with a nearly copropagating pump pulse. Depending on the probe-pump time delay, the probe transmission spectra show the appearance of either specific doublet or coherent dip. The widths of these features are determined by the density-dependent field-matter coupling coefficient and increase during the propagation. Besides that, the widths of the coherent features, which appear close to the resonance in the broadband probe-spectrum, exceed the absorption-line width, since, under the strong-coupling regime, the frequency of the optical ringing exceeds the rate of incoherent relaxation. Contrary to the stationary strong-field effects, the density- and coordinate-dependent transmission spectra of the probe manifest the importance of the collective oscillations and cannot be obtained in the framework of the single-atom model.Comment: 10 pages, 8 figures, to be published in Phys. Rev.

Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR)

PURPOSE: The Phase 3 ENDEAVOUR study evaluated revusiran, an investigational RNA interference therapeutic targeting hepatic transthyretin (TTR) production, for treating cardiomyopathy caused by hereditary transthyretin-mediated (hATTR) amyloidosis. / METHODS: Patients with hATTR amyloidosis with cardiomyopathy were randomized 2:1 to receive subcutaneous daily revusiran 500 mg (n = 140) or placebo (n = 66) for 5 days over a week followed by weekly doses. Co-primary endpoints were 6-min walk test distance and serum TTR reduction. / RESULTS: Revusiran treatment was stopped after a median of 6.71 months; the study Sponsor prematurely discontinued dosing due to an observed mortality imbalance between treatment arms. Eighteen (12.9%) patients on revusiran and 2 (3.0%) on placebo died during the on-treatment period. Most deaths in both treatment arms were adjudicated as cardiovascular due to heart failure (HF), consistent with the natural history of the disease. A post hoc safety investigation of patients treated with revusiran found that, at baseline, a greater proportion of those who died were ≥ 75 years and showed clinical evidence of more advanced HF compared with those who were alive throughout treatment. Revusiran pharmacokinetic exposures and TTR lowering did not show meaningful differences between patients who died and who were alive. Revusiran did not deleteriously affect echocardiographic parameters, cardiac biomarkers, or frequency of cardiovascular and HF hospitalization events. / CONCLUSIONS: Causes for the observed mortality imbalance associated with revusiran were thoroughly investigated and no clear causative mechanism could be identified. Although the results suggest similar progression of cardiac parameters in both treatment arms, a role for revusiran cannot be excluded. / CLINICAL TRIAL REGISTRATION: NCT02319005