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Several recent studies have examined the steady-state welfare implications of mortality differentials within unfunded Social Security systems, concluding that these differentials undermine the progressivity of the system and make society worse-off relative to alternative public pension schemes. This study is the first to systematically investigate the long-run implications of mortality inequality within the U.S. Social Security system. Utilizing an OLG endogenous growth model of the U.S. economy, I compare the current pay-as-you-go (PAYG) system to versions of the model without either mortality differentials or income inequality. I find that the assumption of mortality homogeneity biases the equilibrium growth rate and welfare analysis. The PAYG system is also compared to a fully funded system based on capital subsidies. The model predicts that PAYG suppresses growth and that, for a given range of subsidy rates, the fully funded system Pareto dominates PAYG in both the medium-run and the long-run. [ABSTRACT FROM AUTHOR]

This paper examines the absorption of foreign aid in the presence of formal and informal production. Calibrating a two‐sector open economy model to 67 aid‐recipient countries for 1990–2019, we show that an increase in foreign aid drives resources into the informal sector, and away from the formal sector. With untied aid, the expansion of the informal sector can lead to an economic contraction through the Dutch Disease effect. An economic expansion with an increase in the share of formal production can be attained by re‐allocating existing aid to public investment rather than an increase in the aggregate level of aid. [ABSTRACT FROM AUTHOR]

A coupledwind‐wave modeling system is used to simulate 23 years of storms and estimate offshore extreme wind statistics. In this system, the atmospheric Weather Research and Forecasting (WRF) model and Spectral Wave model for Near shore (SWAN) are coupled, through a wave boundary layer model (WBLM) that is implemented in SWAN. The WBLM calculates momentum and turbulence kinetic energy budgets, using them to transfer wave‐induced stress to the atmospheric modeling. While such coupling has a trivial impact on the wind modeling for 10‐m wind speeds less than 20 ms−1, the effect becomes appreciable for stronger winds—both compared with uncoupled WRF modeling and with standard parameterization schemes for roughness length. The coupled modeling output is shown to be satisfactory compared with measurements, in terms of the distribution of surface‐drag coefficient with wind speed. The coupling is also shown to be important for estimation of extreme winds offshore, where the WBLM‐coupled results match observations better than results from noncoupled modeling, as supported by measurements from a number of stations. [ABSTRACT FROM AUTHOR]

We define and demonstrate a procedure for quick assessment of site-specific lifetime fatigue loads using simplified load mapping functions (surrogate models), trained by means of a database with high-fidelity load simulations. The performance of five surrogate models is assessed by comparing site-specific lifetime fatigue load predictions at 10 sites using an aeroelastic model of the DTU 10MW reference wind turbine. The surrogate methods are polynomial chaos expansion, quadratic response surface, universal Kriging, importance sampling, and nearest-neighbor interpolation. Practical bounds for the database and calibration are defined via nine environmental variables, and their relative effects on the fatigue loads are evaluated by means of Sobol sensitivity indices. Of the surrogate-model methods, polynomial chaos expansion provides an accurate and robust performance in prediction of the different site-specific loads. Although the Kriging approach showed slightly better accuracy, it also demanded more computational resources. [ABSTRACT FROM AUTHOR]

Study Question: What are the characteristics of progesterone-induced (CatSper-mediated) single cell [Ca2+]i signals in spermatozoa from sub-fertile men and how do they relate to fertilizing ability?Summary Answer: Single cell analysis of progesterone-induced (CatSper-mediated) [Ca2+]i showed that reduced progesterone-sensitivity is a common feature of sperm from sub-fertile patients and is correlated with fertilization rate.What Is Known Already: Stimulation with progesterone is a widely used method for assessing [Ca2+]i mobilization by activation of CatSper in human spermatozoa. Although data are limited, sperm population studies have indicated an association of poor [Ca2+]i response to progesterone with reduced fertilization ability.Study Design, Size, Duration: This was a cohort study using semen samples from 21 donors and 101 patients attending the assisted conception unit at Ninewells Hospital Dundee who were undergoing ART treatment. Patients were recruited from January 2016 to June 2017.Participants/materials, Setting, Methods: Semen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service (EoSRES) REC1. [Ca2+]i responses were examined by single cell imaging and motility parameters assessed by computer-assisted sperm analysis (CASA).Main Results and the Role Of Chance: For analysis, patient samples were divided into three groups IVF(+ve) (successful fertilization; 62 samples), IVF-FF (failed fertilization; eight samples) and ICSI (21 samples). A further 10 IVF samples showed large, spontaneous [Ca2+]i oscillations and responses to progesterone could not be analysed. All patient samples loaded with the [Ca2+]i-indicator fluo4 responded to progesterone stimulation with a biphasic increase in fluorescence (transient followed by plateau) which resembled that seen in progesterone-stimulated donor samples. The mean normalized response (progesterone-induced increase in fluorescence normalized to resting level) was significantly smaller in IVF-FF and ICSI patient groups than in donors. All samples were further analysed by plotting, for each cell, the relationship between resting fluorescence intensity and the progesterone-induced fluorescence increment. In donor samples these plots overlaid closely and had a gradient of ≈ 2 and plots for most IVF(+ve) samples closely resembled the donor distribution. However, in a subset (≈ 10%) of IVF(+ve) samples, 3/8 IVF-FF samples and one-third of ICSI samples the gradient of the plot was significantly lower, indicating that the response to progesterone of the cells in these samples was abnormally small. Examination of the relationship between gradient (regression coefficient of the plot) in IVF samples and fertilization rate showed a positive correlation. In IVF-FF and ICSI groups, the proportion of cells in which a response to progesterone could be detected was significantly lower than in donors and IVF (+ve) patients. Approximately 20% of cells in donor, IVF(+ve) and ICSI samples generated [Ca2+]i oscillations when challenged with progesterone but in IVF-FF samples only ≈ 10% of cells generated oscillations and there was a significantly greater proportion of samples where no oscillations were observed. Levels of hyperactivated motility were lower in IVF(+ve) and IVF-FF groups compared to controls, IVF-FF also having lower levels than IVF(+ve).Limitations, Reasons For Caution: This is an in vitro study and caution must be taken when extrapolating these results in vivo.Wider Implications Of the Findings: This study reveals important details of impaired [Ca2+]i signalling in sperm from sub-fertile men that cannot be detected in population studies.Study Funding/competing Interest(s): This study was funded by a MRC project grant (MR/M012492/1; MR/K013343/1). Additional funding was provided by Chief Scientist Office/NHS research Scotland. [ABSTRACT FROM AUTHOR]

Study Question: Does progesterone in human follicular fluid (hFF) activate CatSper and do other components of hFF modulate this effect and/or contribute separately to hFF-induced Ca2+ signaling?Summary Answer: hFF potently stimulates CatSper and increases [Ca2+]i, primarily due to high concentrations of progesterone, however, other components of hFF also contribute to [Ca2+]i signaling, including modulation of CatSper channel activity and inhibition of [Ca2+]i oscillations.What Is Known Already: CatSper, the principal Ca2+ channel in spermatozoa, is progesterone-sensitive and essential for fertility. Both hFF and progesterone, which is present in hFF, influence sperm function and increase their [Ca2+]i.Study Design, Size, Duration: This basic medical research study used semen samples from >40 donors and hFF from >50 patients who were undergoing surgical oocyte retrieval for IVF/ICSI.Participants/materials, Setting, Methods: Semen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service REC1. Activities of CatSper and KSper were assessed by patch clamp electrophysiology. Sperm [Ca2+]i responses were examined in sperm populations and single cells. Computer-assisted sperm analysis (CASA) parameters and penetration into viscous media were used to assess functional effects.Main Results and the Role Of Chance: hFF and progesterone significantly potentiated CatSper currents. Under quasi-physiological conditions, hFF (up to 50%) failed to alter membrane K+ conductance or current reversal potential. hFF and progesterone (at an equivalent concentration) stimulated similar biphasic [Ca2+]i signals both in sperm populations and single cells. At a high hFF concentration (10%), the sustained (plateau) component of the [Ca2+]i signal was consistently greater than that induced by progesterone alone. In single cell recordings, 1% hFF-induced [Ca2+]i oscillations similarly to progesterone but with 10% hFF generation of [Ca2+]i oscillations was suppressed. After treatment to 'strip' lipid-derived mediators, hFF failed to significantly stimulate CatSper currents but induced small [Ca2+]i responses that were greater than those induced by the equivalent concentration of progesterone after stripping. Similar [Ca2+]i responses were observed when sperm pretreated with 3 μM progesterone (to desensitize progesterone responses) were stimulated with hFF or stripped hFF. hFF stimulated viscous media penetration and was more effective than the equivalent does of progesterone.Large Scale Data: N/A.Limitations, Reasons For Caution: This was an in vitro study. Caution must be taken when extrapolating these results in vivo.Wider Implications Of the Findings: This study directly demonstrates that hFF activates CatSper and establishes that the biologically important effects of hFF reflect, at least in part, action on this channel, primarily via progesterone. However, these experiments also demonstrate that other components of hFF both contribute to the [Ca2+]i signal and modulate the activation of CatSper. Simple in vitro experiments performed out of the context of the complex in vivo environment need to be interpreted with caution.Study Funding/competing Interest(s): Funding was provided by MRC (MR/K013343/1, MR/012492/1) (S.G.B., S.J.P., C.L.R.B.) and University of Abertay (sabbatical for S.G.B.). Additional funding was provided by TENOVUS SCOTLAND (S.M.D.S.), Chief Scientist Office/NHS Research Scotland (S.M.D.S). C.L.R.B. is EIC of MHR and Chair of the WHO ESG on Diagnosis of Male infertility. The remaining authors have no conlicts of interest. [ABSTRACT FROM AUTHOR]

Study Question: Can pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility?Summary Answer: High-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility.What Is Known Already: There is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform.Study Design, Size, Duration: Spermatozoa were obtained from healthy volunteer research donors and subfertile patients undergoing IVF/ICSI at a hospital-assisted reproductive techniques clinic between January 2012 and November 2016.Participants/materials, Setting, Methods: A HTS assay was developed and validated using intracellular calcium ([Ca2+]i) as a surrogate for motility in human spermatozoa. Calcium fluorescence was detected using a Flexstation microplate reader (384-well platform) and compared with responses evoked by progesterone, a compound known to modify a number of biologically relevant behaviours in human spermatozoa. Hit compounds identified following single point drug screen (10 μM) of an ion channel-focussed library assembled by the University of Dundee Drug Discovery Unit were rescreened to ensure potency using standard 10 point half-logarithm concentration curves, and tested for purity and integrity using liquid chromatography and mass spectrometry. Hit compounds were grouped by structure activity relationships and five representative compounds then further investigated for direct effects on spermatozoa, using computer-assisted sperm assessment, sperm penetration assay and whole-cell patch clamping.Main Results and the Role Of Chance: Of the 3242 ion channel library ligands screened, 384 compounds (11.8%) elicited a statistically significant increase in calcium fluorescence, with greater than 3× median absolute deviation above the baseline. Seventy-four compounds eliciting ≥50% increase in fluorescence in the primary screen were rescreened and evaluated further, resulting in 48 hit compounds that produced a concentration-dependent increase in [Ca2+]i. Sperm penetration studies confirmed in vitro exposure to two hit compounds (A and B) resulted in significant improvement in functional motility in spermatozoa from healthy volunteer donors (A: 1 cm penetration index 2.54, 2 cm penetration index 2.49; P < 0.005 and B: 1 cm penetration index 2.1, 2 cm penetration index 2.6; P < 0.005), but crucially, also in patient samples from those undergoing fertility treatment (A: 1 cm penetration index 2.4; P = 0.009, 2 cm penetration index 3.6; P = 0.02 and B: 1 cm penetration index 2.2; P = 0.0004, 2 cm penetration index 3.6; P = 0.002). This was primarily as a result of direct or indirect CatSper channel action, supported by evidence from electrophysiology studies of individual sperm.Limitations, Reasons For Caution: Increase and fluxes in [Ca2+]i are fundamental to the regulation of sperm motility and function, including acrosome reaction. The use of calcium signalling as a surrogate for sperm motility is acknowledged as a potential limitation in this study.Wider Implications Of the Findings: We conclude that HTS can robustly, efficiently, identify novel compounds that increase [Ca2+]i in human spermatozoa and functionally modify motility, and propose its use as a cornerstone to build and transform much-needed drug discovery for male infertility.Study Funding/competing Interest(s): The majority of the data were obtained using funding from TENOVUS Scotland and Chief Scientist Office NRS Fellowship. Additional funding was provided by NHS Tayside, MRC project grants (MR/K013343/1, MR/012492/1) and University of Abertay. The authors declare that there is no conflict of interest.Trail Registration Number: N/A. [ABSTRACT FROM AUTHOR]

A new k- ϵ model is introduced that is consistent with Monin-Obukhov similarity theory (MOST). The proposed k- ϵ model is compared with another k- ϵ model that was developed in an attempt to maintain inlet profiles compatible with MOST. It is shown that the previous k- ϵ model is not consistent with MOST for unstable conditions, while the proposed k- ϵ model can maintain MOST inlet profiles over distances of 50km. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this paper, the impact of atmospheric stability on a wind turbine wake is studied experimentally and numerically. The experimental approach is based on full-scale (nacelle based) pulsed lidar measurements of the wake flow field of a stall-regulated 500 kW turbine at the DTU Wind Energy, Risø campus test site. Wake measurements are averaged within a mean wind speed bin of 1 m s−1 and classified according to atmospheric stability using three different metrics: the Obukhov length, the Bulk-Richardson number and the Froude number. Three test cases are subsequently defined covering various atmospheric conditions. Simulations are carried out using large eddy simulation and actuator disk rotor modeling. The turbulence properties of the incoming wind are adapted to the thermal stratification using a newly developed spectral tensor model that includes buoyancy effects. Discrepancies are discussed, as basis for future model development and improvement. Finally, the impact of atmospheric stability on large-scale and small-scale wake flow characteristics is presently investigated. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The newly developed k- ε- f P eddy viscosity model is applied to double wind turbine wake configurations in a neutral atmospheric boundary layer, using a Reynolds-Averaged Navier-Stokes solver. The wind turbines are represented by actuator disks. A proposed variable actuator disk force method is employed to estimate the power production of the interacting wind turbines, and the results are compared with two existing methods: a method based on tabulated airfoil data and a method based on the axial induction from 1D momentum theory. The proposed method calculates the correct power, while the other two methods overpredict it. The results of the k- ε- f P eddy viscosity model are also compared with the original k- ε eddy viscosity model and large-eddy simulations. Compared to the large-eddy simulations-predicted velocity and power deficits, the k- ε- f P is superior to the original k- ε model. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The recently developed k- ϵ- f P eddy-viscosity model is applied to one on-shore and two off-shore wind farms. The results are compared with power measurements and results of the standard k- ϵ eddy-viscosity model. In addition, the wind direction uncertainty of the measurements is used to correct the model results with a Gaussian filter. The standard k- ϵ eddy-viscosity model underpredicts the power deficit of the first downstream wind turbines, whereas the k- ϵ- f P eddy-viscosity model shows a good agreement with the measurements. However, the difference in the power deficit predicted by the turbulence models becomes smaller for wind turbines that are located further downstream. Moreover, the difference between the capability of the turbulence models to estimate the wind farm efficiency reduces with increasing wind farm size and wind turbine spacing. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An improved k- ϵ turbulence model is developed and applied to a single wind turbine wake in a neutral atmospheric boundary layer using a Reynolds averaged Navier-Stokes solver. The proposed model includes a flow-dependent C μ that is sensitive to high velocity gradients, e.g., at the edge of a wind turbine wake. The modified k- ϵ model is compared with the original k- ϵ eddy viscosity model, Large-Eddy Simulations and field measurements using eight test cases. The comparison shows that the velocity wake deficits, predicted by the proposed model are much closer to the ones calculated by the Large-Eddy Simulation and those observed in the measurements, than predicted by the original k- ϵ model. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]