Clocked Atom Delivery to a Photonic Crystal Waveguide

Experiments and numerical simulations are described that develop quantitative understanding of atomic motion near the surfaces of nanoscopic photonic crystal waveguides (PCWs). Ultracold atoms are delivered from a moving optical lattice into the PCW. Synchronous with the moving lattice, transmission spectra for a guided-mode probe field are recorded as functions of lattice transport time and frequency detuning of the probe beam. By way of measurements such as these, we have been able to validate quantitatively our numerical simulations, which are based upon detailed understanding of atomic trajectories that pass around and through nanoscopic regions of the PCW under the influence of optical and surface forces. The resolution for mapping atomic motion is roughly 50 nm in space and 100 ns in time. By introducing auxiliary guided mode (GM) fields that provide spatially varying AC-Stark shifts, we have, to some degree, begun to control atomic trajectories, such as to enhance the flux into to the central vacuum gap of the PCW at predetermined times and with known AC-Stark shifts. Applications of these capabilities include enabling high fractional filling of optical trap sites within PCWs, calibration of optical fields within PCWs, and utilization of the time-dependent, optically dense atomic medium for novel nonlinear optical experiments

A comparison of single-cycle versus multiple-cycle proof testing strategies

An evaluation of single-cycle and multiple-cycle proof testing (MCPT) strategies for SSME components is described. Data for initial sizes and shapes of actual SSME hardware defects are analyzed statistically. Closed-form estimates of the J-integral for surface flaws are derived with a modified reference stress method. The results of load- and displacement-controlled stable crack growth tests on thin IN-718 plates with deep surface flaws are summarized. A J-resistance curve for the surface-cracked configuration is developed and compared with data from thick compact tension specimens. The potential for further crack growth during large unload/reload cycles is discussed, highlighting conflicting data in the literature. A simple model for ductile crack growth during MCPT based on the J-resistance curve is used to study the potential effects of key variables. The projected changes in the crack size distribution during MCPT depend on the interactions between several key parameters, including the number of proof cycles, the nature of the resistance curve, the initial crack size distribution, the component boundary conditions (load vs. displacement control), and the magnitude of the applied load or displacement. The relative advantages of single-cycle and multiple-cycle proof testing appear to be specific, therefore, to individual component geometry, material, and loading

Cellular-Automata model for dense-snow avalanches

This paper introduces a three-dimensional model for simulating dense-snow avalanches, based on the numerical method of cellular automata. This method allows one to study the complex behavior of the avalanche by dividing it into small elements, whose interaction is described by simple laws, obtaining a reduction of the computational power needed to perform a three-dimensional simulation. Similar models by several authors have been used to model rock avalanches, mud and lava flows, and debris avalanches. A peculiar aspect of avalanche dynamics, i.e., the mechanisms of erosion of the snowpack and deposition of material from the avalanche is taken into account in the model. The capability of the proposed approach has been illustrated by modeling three documented avalanches that occurred in Susa Valley (Western Italian Alps). Despite the qualitative observations used for calibration, the proposed method is able to reproduce the correct three-dimensional avalanche path, using a digital terrain model, and the order of magnitude of the avalanche deposit volume

Analysis of small crack behavior for airframe applications

The small fatigue crack problem is critically reviewed from the perspective of airframe applications. Different types of small cracks-microstructural, mechanical, and chemical-are carefully defined and relevant mechanisms identified. Appropriate analysis techniques, including both rigorous scientific and practical engineering treatments, are briefly described. Important materials data issues are addressed, including increased scatter in small crack data and recommended small crack test methods. Key problems requiring further study are highlighted

The role of osteoanabolic agents in the management of patients with osteoporosis

Reducing fracture risk is the objective of osteoporosis treatment. Bone-forming osteoporosis drugs increase bone mass, restore bone microarchitecture, and reduce fracture risk more effectively than oral bisphosphonates, providing strong justification for the use of these agents as the initial therapy or after anti-remodeling agents in patients at very high risk of fracture. At the end of a 12-to-24-month course of osteoanabolic therapy, transitioning to a potent anti-remodeling agent maintains and enhances the treatment benefit. This review describes the clinical applications of osteoanabolic therapy for osteoporosis

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet

Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy

Odanacatib for the treatment of postmenopausal osteoporosis: Development history and design and participant characteristics of LoFT, the Long-term odanacatib Fracture Trial

Summary: Odanacatib is a cathepsin K inhibitor investigated for the treatment of postmenopausal osteoporosis. Phase 2 data indicate that 50 mg once weekly inhibits bone resorption and increases bone mineral density, with only a transient decrease in bone formation. We describe the background, design and participant characteristics for the phase 3 registration trial. Introduction: Odanacatib (ODN) is a selective cathepsin K inhibitor being evaluated for the treatment of osteoporosis. In a phase 2 trial, ODN 50 mg once weekly reduced bone resorption while preserving bone formation and progressively increased BMD over 5 years. We describe the phase III Long-Term ODN Fracture Trial (LOFT), an event-driven, randomized, blinded placebo-controlled trial, with preplanned interim analyses to permit early termination if significant fracture risk reduction was demonstrated. An extension was planned, with participants remaining on their randomized treatment for up to 5 years, then transitioning to open-label ODN. Methods: The three primary outcomes were radiologically determined vertebral, hip, and clinical non-vertebral fractures. Secondary end points included clinical vertebral fractures, BMD, bone turnover markers, and safety and tolerability, including bone histology. Participants were women, 65 years or older, with a BMD T-score ≤−2.5 at the total hip (TH) or femoral neck (FN) or with a prior radiographic vertebral fracture and a T-score ≤−1.5 at the TH or FN. They were randomized to ODN or placebo tablets. All received weekly vitamin D3 (5600 international units (IU)) and daily calcium supplements as needed to ensure a daily intake of approximately 1200 mg. Results: Altogether, 16,713 participants were randomized at 387 centers. After a planned interim analysis, an independent data monitoring committee recommended that the study be stopped early due to robust efficacy and a favorable benefit/risk profile. Following the base study closeout, 8256 participants entered the study extension. Conclusions: This report details the background and study design of this fracture end point trial and describes the baseline characteristics of its participants

Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss.

INTRODUCTION: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies. Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of-the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects. Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk