Cell Death in the Embryonic Developing Limb

In amniote vertebrates, the development of form and structure of the limb bud is accompanied by precise patterns of massive mesodermal cell death with morphological features of apoptosis. These areas of cell death appear to eliminate undifferentiated cells which are required only for a limited time period of limb development. Predictable skeletal and morphological anomalies of the limb occur when the pattern of cell death is modified in mutant species or under experimental conditions. Most evidence points to the occurrence of local triggering mechanisms to account for the establishment of the areas of cell death and the subsequent activation of cell death genes. Modifications of the extracellular matrix and diminution in the contribution of growth factors by neighbouring tissues appear as the most likely potential candidates for triggering the cell death program. Information on the genetical basis of cell death in the developing limb is very scarce. Among the increasing number of cell death genes identified in other cell death systems, such as p-53 and the ced-3/ICE and ced-9/bcl-2 gene families, only bcl-2 has been studied in detail during limb development and yet, the information obtained is contradictory. Bcl-2 is not expressed in the areas of cell death of the developing limb, but normal limbs develop in mice with disruption of the bcl-2 gene. Obviously, the clarification of the role of the cell death genes constitute a major task in future studies of cell death in the developing limb

Recent Technological Developments on LGAD and iLGAD Detectors for Tracking and Timing Applications

This paper reports the last technological development on the Low Gain Avalanche Detector (LGAD) and introduces a new architecture of these detectors called inverse-LGAD (iLGAD). Both approaches are based on the standard Avalanche Photo Diodes (APD) concept, commonly used in optical and X-ray detection applications, including an internal multiplication of the charge generated by radiation. The multiplication is inherent to the basic n++-p+-p structure, where the doping profile of the p+ layer is optimized to achieve high field and high impact ionization at the junction. The LGAD structures are optimized for applications such as tracking or timing detectors for high energy physics experiments or medical applications where time resolution lower than 30 ps is required. Detailed TCAD device simulations together with the electrical and charge collection measurements are presented through this work.Comment: Keywords: silicon detectors, avalanche multiplication, timing detectors, tracking detectors. 8 pages. 8 Figure

The nature of domain walls in ultrathin ferromagnets revealed by scanning nanomagnetometry

The recent observation of current-induced domain wall (DW) motion with large velocity in ultrathin magnetic wires has opened new opportunities for spintronic devices. However, there is still no consensus on the underlying mechanisms of DW motion. Key to this debate is the DW structure, which can be of Bloch or N\'eel type, and dramatically affects the efficiency of the different proposed mechanisms. To date, most experiments aiming to address this question have relied on deducing the DW structure and chirality from its motion under additional in-plane applied fields, which is indirect and involves strong assumptions on its dynamics. Here we introduce a general method enabling direct, in situ, determination of the DW structure in ultrathin ferromagnets. It relies on local measurements of the stray field distribution above the DW using a scanning nanomagnetometer based on the Nitrogen-Vacancy defect in diamond. We first apply the method to a Ta/Co40Fe40B20(1 nm)/MgO magnetic wire and find clear signature of pure Bloch DWs. In contrast, we observe left-handed N\'eel DWs in a Pt/Co(0.6 nm)/AlOx wire, providing direct evidence for the presence of a sizable Dzyaloshinskii-Moriya interaction (DMI) at the Pt/Co interface. This method offers a new path for exploring interfacial DMI in ultrathin ferromagnets and elucidating the physics of DW motion under current.Comment: Main text and Supplementary Information, 33 pages and 12 figure

Cost-Utility Analysis of a Medication Review with Follow-Up Service for Older Adults with Polypharmacy in Community Pharmacies in Spain: The conSIGUE Program

© 2015, Springer International Publishing Switzerland. Background: The concept of pharmaceutical care is operationalized through pharmaceutical professional services, which are patient-oriented to optimize their pharmacotherapy and to improve clinical outcomes. Objective: The objective of this study was to estimate the incremental cost-effectiveness ratio (ICER) of a medication review with follow-up (MRF) service for older adults with polypharmacy in Spanish community pharmacies against the alternative of having their medication dispensed normally. Methods: The study was designed as a cluster randomized controlled trial, and was carried out over a time horizon of 6 months. The target population was older adults with polypharmacy, defined as individuals taking five or more medicines per day. The study was conducted in 178 community pharmacies in Spain. Cost-utility analysis adopted a health service perspective. Costs were in euros at 2014 prices and the effectiveness of the intervention was estimated as quality-adjusted life-years (QALYs). In order to analyze the uncertainty of ICER results, we performed a non-parametric bootstrapping with 5000 replications. Results: A total of 1403 older adults, aged between 65 and 94 years, were enrolled in the study: 688 in the intervention group (IG) and 715 in the control group (CG). By the end of the follow-up, both groups had reduced the mean number of prescribed medications they took, although this reduction was greater in the IG (0.28 ± 1.25 drugs; p < 0.001) than in the CG (0.07 ± 0.95 drugs; p = 0.063). Older adults in the IG saw their quality of life improved by 0.0528 ± 0.20 (p < 0.001). In contrast, the CG experienced a slight reduction in their quality of life: 0.0022 ± 0.24 (p = 0.815). The mean total cost was €977.57 ± 1455.88 for the IG and €1173.44 ± 3671.65 for the CG. In order to estimate the ICER, we used the costs adjusted for baseline medications and QALYs adjusted for baseline utility score, resulting in a mean incremental total cost of −€250.51 ± 148.61 (95 % CI −541.79 to 40.76) and a mean incremental QALY of 0.0156 ± 0.004 (95 % CI 0.008–0.023). Regarding the results from the cost-utility analysis, the MRF service emerged as the dominant strategy. Conclusion: The MRF service is an effective intervention for optimizing prescribed medication and improving quality of life in older adults with polypharmacy in community pharmacies. The results from the cost-utility analysis suggest that the MRF service is cost effective

Spin-orbit torques for current parallel and perpendicular to a domain wall

We report field- and current-induced domain wall (DW) depinning experiments in Ta/Co20Fe60B20/MgO nanowires through a Hall cross geometry. While purely field-induced depinning shows no angular dependence on in-plane fields, the effect of the current depends crucially on the internal DW structure, which we manipulate by an external magnetic in-plane field. We show for the first time depinning measurements for a current sent parallel to the DW and compare its depinning efficiency with the conventional case of current flowing perpendicularly to the DW. We find that the maximum efficiency is similar for both current directions within the error bars, which is in line with a dominating damping-like spin-orbit torque (SOT) and indicates that no large additional torques arise for currents parallel to the DW. Finally, we find a varying dependence of the maximum depinning efficiency angle for different DWs and pinning levels. This emphasizes the importance of our full angular scans compared to previously used measurements for just two field directions (parallel and perpendicular to the DW) and shows the sensitivity of the spin-orbit torque to the precise DW structure and pinning sites.Comment: 11 pages, 3 figure

Ultrasound assisted one-pot synthesis of benzo-fused indole-4, 9-dinones from 1,4-naphthoquinone and α-aminoacetals

A one-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinone with α-aminoacetals has been developed. This method provides a straightforward synthesis of benzo[f]indole-4,9-diones via intramolecular nucleophilic attack of aminoquinones to aldehydes under mild reaction conditions. The detailed mechanism was also investigated

The Green Bank Northern Celestial Cap Pulsar Survey - I: Survey Description, Data Analysis, and Initial Results

We describe an ongoing search for pulsars and dispersed pulses of radio emission, such as those from rotating radio transients (RRATs) and fast radio bursts (FRBs), at 350 MHz using the Green Bank Telescope. With the Green Bank Ultimate Pulsar Processing Instrument, we record 100 MHz of bandwidth divided into 4,096 channels every 81.92 $\mu s$. This survey will cover the entire sky visible to the Green Bank Telescope ($\delta > -40^\circ$, or 82% of the sky) and outside of the Galactic Plane will be sensitive enough to detect slow pulsars and low dispersion measure ($<$30 $\mathrm{pc\,cm^{-3}}$) millisecond pulsars (MSPs) with a 0.08 duty cycle down to 1.1 mJy. For pulsars with a spectral index of $-$1.6, we will be 2.5 times more sensitive than previous and ongoing surveys over much of our survey region. Here we describe the survey, the data analysis pipeline, initial discovery parameters for 62 pulsars, and timing solutions for 5 new pulsars. PSR J0214$+$5222 is an MSP in a long-period (512 days) orbit and has an optical counterpart identified in archival data. PSR J0636$+$5129 is an MSP in a very short-period (96 minutes) orbit with a very low mass companion (8 $M_\mathrm{J}$). PSR J0645$+$5158 is an isolated MSP with a timing residual RMS of 500 ns and has been added to pulsar timing array experiments. PSR J1434$+$7257 is an isolated, intermediate-period pulsar that has been partially recycled. PSR J1816$+$4510 is an eclipsing MSP in a short-period orbit (8.7 hours) and may have recently completed its spin-up phase.Comment: 18 pages, 10 figures, 5 tables, accepted by Ap

Mass hierarchy, 2-3 mixing and CP-phase with Huge Atmospheric Neutrino Detectors

We explore the physics potential of multi-megaton scale ice or water Cherenkov detectors with low ($\sim 1$ GeV) threshold. Using some proposed characteristics of the PINGU detector setup we compute the distributions of events versus neutrino energy $E_\nu$ and zenith angle $\theta_z$, and study their dependence on yet unknown neutrino parameters. The $(E_\nu - \theta_z)$ regions are identified where the distributions have the highest sensitivity to the neutrino mass hierarchy, to the deviation of the 2-3 mixing from the maximal one and to the CP-phase. We evaluate significance of the measurements of the neutrino parameters and explore dependence of this significance on the accuracy of reconstruction of the neutrino energy and direction. The effect of degeneracy of the parameters on the sensitivities is also discussed. We estimate the characteristics of future detectors (energy and angle resolution, volume, etc.) required for establishing the neutrino mass hierarchy with high confidence level. We find that the hierarchy can be identified at $3\sigma$ -- $10\sigma$ level (depending on the reconstruction accuracies) after 5 years of PINGU operation.Comment: 39 pages, 21 figures. Description of Fig.3 correcte

Mass hierarchy discrimination with atmospheric neutrinos in large volume ice/water Cherenkov detectors

Large mass ice/water Cherenkov experiments, optimized to detect low energy (1-20 GeV) atmospheric neutrinos, have the potential to discriminate between normal and inverted neutrino mass hierarchies. The sensitivity depends on several model and detector parameters, such as the neutrino flux profile and normalization, the Earth density profile, the oscillation parameter uncertainties, and the detector effective mass and resolution. A proper evaluation of the mass hierarchy discrimination power requires a robust statistical approach. In this work, the Toy Monte Carlo, based on an extended unbinned likelihood ratio test statistic, was used. The effect of each model and detector parameter, as well as the required detector exposure, was then studied. While uncertainties on the Earth density and atmospheric neutrino flux profiles were found to have a minor impact on the mass hierarchy discrimination, the flux normalization, as well as some of the oscillation parameter (\Delta m^2_{31}, \theta_{13}, \theta_{23}, and \delta_{CP}) uncertainties and correlations resulted critical. Finally, the minimum required detector exposure, the optimization of the low energy threshold, and the detector resolutions were also investigated.Comment: 23 pages, 16 figure