Communication and control system for a 15-channel hermetic retinal prosthesis

A small, hermetic, wirelessly-controlled retinal prosthesis has been developed for pre-clinical studies in Yucatan minipigs. The device was attached conformally to the outside of the eye in the socket and received both power and data wirelessly from external sources. Based on the received image data, the prosthesis drove a subretinal thin-film polyimide array of sputtered iridium oxide stimulating electrodes. The implanted device included a hermetic titanium case containing a 15-channel stimulator and receiver chip and discrete circuit components. Feedthroughs in the hermetic case connected the chip to secondary power- and data-receiving coils, which coupled to corresponding external power and data coils driven by power amplifiers. Power was delivered by a 125 kHz carrier, and data were delivered by amplitude shift keying of a 15.5 MHz carrier at 100 kbps. Stimulation pulse strength, duration and frequency were programmed wirelessly from an external computer system. The final assembly was tested in vitro in physiological saline and in vivo in two minipigs for up to five and a half months by measuring stimulus artifacts generated by the implant's current drivers.United States. Dept. of Veteran AffairsUnited states. Dept. of Veterans Affairs. Boston Healthcare SystemNational Institutes of Health (U.S.)United States. Dept. of DefenseMassachusetts Lions Foundatio

A phase 3, open-label, randomized trial to evaluate the safety and efficacy of levofloxacin inhalation solution (APT-1026) versus tobramycin inhalation solution in stable cystic fibrosis patients

Background: Inhaled antibiotics are standard of care for persons with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa airway infection. APT-1026 (levofloxacin inhalation solution, LIS) is fluoroquinolone in development. We compared the safety and efficacy of LIS to tobramycin inhalation solution (TIS) in persons ≥12 years old with CF and chronic P. aeruginosa infection. Methods: This multinational, randomized (2:1), non-inferiority study compared LIS and TIS over three 28-day on/off cycles. Day 28 FEV1 % predicted change was the primary endpoint. Time to exacerbation and patient-reported quality of life superiority were among secondary endpoints. Results: Baseline demographics for 282 subjects were comparable. Non-inferiority was demonstrated (1.86% predicted mean FEV1 difference [95% CI −0.66 to 4.39%]). LIS was well-tolerated, with dysguesia (taste distortion) the most frequent adverse event. Conclusions: LIS is a safe and effective therapy for the management of CF patients with chronic P. aeruginosa

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Root-Associated Streptomyces Isolates Harboring melC Genes Demonstrate Enhanced Plant Colonization

Streptomycetaceae assemble into the internal, root endophytic compartment of a wide variety of plants grown in soils worldwide, suggesting their ability to survive during root microbiome assembly. A previous study found that among four nonpathogenic, root-isolated Streptomyces strains (303, 299, CL18, and 136), only 303 and 299 colonized endophytic root tissue of the majority of Arabidopsis thaliana roots when inoculated with 34 other bacterial isolates. Here we demonstrate that 303 and 299 also colonize significantly more in singly inoculated A. thaliana seedlings. The genomes of melanin-producing 303 and 299 each contain two copies of the gene encoding tyrosinase (melC2 and melD2), an enzyme necessary for melanin biosynthesis in Streptomyces. These genes were not found in the genomes of 136 or CL18. Tyrosinase activity was detected in 303 and 299 whole cell and supernatant protein extracts, suggesting functional intracellular and extracellular enzymes.. Because tyrosinase oxidizes phenolic compounds and Streptomyces colonization of A. thaliana appears to be influenced by the phenolic compound salicylic acid (SA), we measured direct sensitivity of Streptomyces isolates to the phenolic compounds catechol, ferulic acid (FA), and SA in vitro. While both 303 and 299 showed higher numbers of surviving colonies than CL18 and 136 in the presence of catechol, only 303 demonstrated a higher number of surviving colonies when isolates were challenges with FA and SA. Finally, when seedlings were singly inoculated with a collection of related plant-associated Streptomyces isolates, colonization was significantly higher in isolates possessing two tyrosinase gene copies than isolates with zero or one gene copy. Overall, we describe a connection between microbial tyrosinase activity and increased seedling colonization of nonpathogenic Streptomyces isolates in A. thaliana. We propose tyrosinase activity in Streptomyces partially protects against harmful plant-produced phenolic compounds as they transition into an endophytic lifestyle

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

Changes in body composition and performance with supplemental HMB-FA+ATP (Manuscript Clarification)

Additional co-authors: Matthew D. Vukovich, Colin Wilborn, and Darryn S. Willoughb

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Genomic insights into rapid speciation within the world’s largest tree genus Syzygium

Species radiations, despite immense phenotypic variation, can be difficult to resolve phylogenetically when genetic change poorly matches the rapidity of diversification. Genomic potential furnished by palaeopolyploidy, and relative roles for adaptation, random drift and hybridisation in the apportionment of genetic variation, remain poorly understood factors. Here, we study these aspects in a model radiation, Syzygium, the most species-rich tree genus worldwide. Genomes of 182 distinct species and 58 unidentified taxa are compared against a chromosome-level reference genome of the sea apple, Syzygium grande. We show that while Syzygium shares an ancient genome doubling event with other Myrtales, little evidence exists for recent polyploidy events. Phylogenomics confirms that Syzygium originated in Australia-New Guinea and diversified in multiple migrations, eastward to the Pacific and westward to India and Africa, in bursts of speciation visible as poorly resolved branches on phylogenies. Furthermore, some sublineages demonstrate genomic clines that recapitulate cladogenetic events, suggesting that stepwise geographic speciation, a neutral process, has been important in Syzygium diversification