Hepcidin: A Critical Regulator of Iron Metabolism during Hypoxia

Iron status affects cognitive and physical performance in humans. Recent evidence indicates that iron balance is a tightly regulated process affected by a series of factors other than diet, to include hypoxia. Hypoxia has profound effects on iron absorption and results in increased iron acquisition and erythropoiesis when humans move from sea level to altitude. The effects of hypoxia on iron balance have been attributed to hepcidin, a central regulator of iron homeostasis. This paper will focus on the molecular mechanisms by which hypoxia affects hepcidin expression, to include a review of the hypoxia inducible factor (HIF)/hypoxia response element (HRE) system, as well as recent evidence indicating that localized adipose hypoxia due to obesity may affect hepcidin signaling and organismal iron metabolism

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

Non-contact technique for characterizing full-field surface deformation of shape memory polymers at elevated and room temperatures

Abstract Thermally activated shape memory polymers (SMPs) can display modulus changes of approximately three orders of magnitude in transitioning from the high modulus, "glassy" state below the glass transition temperature (Tg) to the low modulus, "rubbery" state above the Tg. In the high temperature region, SMPs can achieve strain levels well above 100%. Their complex behavior includes large modulus changes to as low as ∼1 MPa, extremely high strain levels, and path dependent properties, thus precluding the use of traditional strain gages and low-contact force extensometers. The present study presents a comparison of thermomechanical testing techniques developed to characterize the material behavior of SMPs. Specifically, the performance of strain measurements using contact methods (clip-on extensometers and adhesive strain gages) are compared to non-contact methods (laser extensometer and digital image correlation). An MTS environmental chamber with an observation window allows for non-contact optical measurements during testing. A series of tensile tests are performed on a commercial SMP (with a Tg of ∼105 °C) at 25 °C and at 130 °C. It is observed that the clip-on extensometer significantly affects the SMP behavior even in the low temperature, high modulus state. Overall, the laser extensometer provides a robust method for controlling the axial strain in the gage section of the samples at moderate strain rates. The digital image correlation allows for full field measurement of both axial and transverse strains of SMPs over a range of temperatures and strain rates

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

Circulating endothelial cells are elevated in patients with type 2 diabetes mellitus independently of HbA1c

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Vitamin D status in female military personnel during combat training

Vitamin D is an essential nutrient for maintaining bone health. Recent data suggest that vitamin D and calcium supplementation might affect stress fracture incidence in military personnel. Although stress fracture is a health risk for military personnel during training, no study has investigated changes in vitamin D status in Soldiers during United States (US) Army basic combat training (BCT). This longitudinal study aimed to determine the effects of BCT on 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) levels in female Soldiers. Serum 25(OH)D and PTH were assessed in 74 fasted Soldier volunteers before and after an 8-week BCT course conducted between August and October in Columbia, South Carolina. In the total study population, 25(OH)D levels decreased (mean ± SD) from 72.9 ± 30.0 to 63.3 ± 19.8 nmol/L (P < 0.05) and PTH levels increased from 36.2 ± 15.8 to 47.5 ± 21.2 pg/mL (P < 0.05) during BCT. Ethnicity affected changes in vitamin D status (ethnicity-by-time interaction, P < 0.05); 25(OH)D decreased (P < 0.05) in both Hispanic and non-Hispanic whites, but did not change in non-Hispanic blacks. Ethnicity did not affect BCT-induced changes in PTH. These data indicate that vitamin D status in female Soldiers may decline during military training in the late summer and early autumn months in the Southeastern US. Future studies should strive to determine the impact of military clothing and seasonality on vitamin D status, as well as the functional impact of declining vitamin D status on bone health

A pooled analysis of fall incidence from placebo‐controlled trials of denosumab

Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo‐controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo‐controlled period of each trial. A time‐to‐event analysis of first fall and exposure‐adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome

Integrated fiber-mirror ion trap for strong ion-cavity coupling

We present and characterize fiber mirrors and a miniaturized ion-trap design developed to integrate a fiber-based Fabry-Perot cavity (FFPC) with a linear Paul trap for use in cavity-QED experiments with trapped ions. Our fiber-mirror fabrication process not only enables the construction of FFPCs with small mode volumes, but also allows us to minimize the influence of the dielectric fiber mirrors on the trapped-ion pseudopotential. We discuss the effect of clipping losses for long FFPCs and the effect of angular and lateral displacements on the coupling efficiencies between cavity and fiber. Optical profilometry allows us to determine the radii of curvature and ellipticities of the fiber mirrors. From finesse measurements, we infer a single-atom cooperativity of up to 12 for FFPCs longer than 200 μm in length; comparison to cavities constructed with reference substrate mirrors produced in the same coating run indicates that our FFPCs have similar scattering losses. We characterize the birefringence of our fiber mirrors, finding that careful fiber-mirror selection enables us to construct FFPCs with degenerate polarization modes. As FFPCs are novel devices, we describe procedures developed for handling, aligning, and cleaning them. We discuss experiments to anneal fiber mirrors and explore the influence of the atmosphere under which annealing occurs on coating losses, finding that annealing under vacuum increases the losses for our reference substrate mirrors. X-ray photoelectron spectroscopy measurements indicate that these losses may be attributable to oxygen depletion in the mirror coating. Special design considerations enable us to introduce a FFPC into a trapped ion setup. Our unique linear Paul trap design provides clearance for such a cavity and is miniaturized to shield trapped ions from the dielectric fiber mirrors. We numerically calculate the trap potential in the absence of fibers. In the experiment additional electrodes can be used to compensate distortions of the potential due to the fibers. Home-built fiber feedthroughs connect the FFPC to external optics, and an integrated nanopositioning system affords the possibility of retracting or realigning the cavity without breaking vacuum