Optimal dose calibration in radiotherapy

In this paper, the tools provided by the theory of Optimal Experimental Design are applied to a nonlinear calibration model. This is motivated by the need of estimating radiation doses using radiochromic films for radiotherapy purposes. The calibration model is in this case nonlinear and the explanatory variable cannot be worked out explicitly from the model. In this case an experimental design has to be found on the dependent variable. For that, the inverse function theorem will be used to obtain an information matrix to be optimized. Optimal designs on the response variable are computed from two different perspectives, first for fitting the model and estimating each of the parameters and then for predicting the proper dose. While the first is a common point of view in a general context of the Optimal Experimental Design, the latter is actually the main objective of the calibration problem for the practitioners and algorithms for computing these optimal designs are also provided. The optimal designs obtained have just three different points in their support, but practitioners usually demand for more support points. Thus, a methodology for computing space-filling designs is also provided when the support points are forced to follow some mathematical rule, such as arithmetic or geometric sequences. Cross efficiencies of all these designs are computed in order to show their ability for different goals

Wide range group delay tuning in lossy fiber ring resonators

22nd International Conference on Optical Fiber Sensors, OFS 2012, Beijing, China, 15-19 Oct. 2012We demonstrate theoretically and experimentally that a wide-range tuning of group delay values can be achieved in a\ud lossy fiber ring resonator. The tuning mechanism relies simply on varying the loss/coupling ratio in the resonator. This\ud simple structure may be used advantageously in different regimes for many sensing configurations, both for achieving\ud extremely high sensitivity enhancements (by working close to critical coupling, where the group index becomes\ud extremely large) or suppression of undesired refractive index effects (e.g. Kerr effect), by working in the under-coupled\ud regime

Turning a low Q fiber resonator into a high-sensitivity displacement sensor using slow light concepts

High-Q resonators have been widely used for sensing purposes. High Q factors normally lead to sharp spectral peaks which accordingly provide a strong sensitivity in spectral interrogation methods. In this work we employ a low-Q ring resonator to develop a high sensitivity sub-micrometric resolution displacement sensor. We use the slow-light effects occurring close to the critical coupling regime to achieve high sensitivity in the device. By tuning the losses in the cavity close to the critical coupling, extremely high group delay variations can be achieved, which in turn introduce strong enhancements of the absorption of the structure. We first validate the concept using an Optical Vector Analyzer (OVA) and then we propose a simple functional scheme for achieving a low-cost interrogation of this kind of sensors.European CommissionMinisterio de Ciencia e InnovaciónComunidad de Madri

A Nickase Cas9 Gene-Drive System Promotes Super-Mendelian inheritance in Drosophila

CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (\u3e50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a gene-drive that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that generating 5\u27 overhangs in the system yields efficient allelic conversion. The nickase gene-drive arrangement produces large, stereotyped deletions that are advantageous to eliminate viable animals carrying small mutations when targeting essential genes. Our nickase approach should expand the repertoire for gene-drive arrangements aimed at applications in mosquitoes and beyond

Spatiotemporal characteristics of motor actions by blind long jump athletes

Background Blind people depend on spatial and temporal representations to perform activities of daily living and compete in sport. Objective The aim of this study is to determine the spatiotemporal characteristics of long jumps performed by blind athletes and compare findings with those reported for sighted athletes. Methods We analysed a sample of 12 male athletes competing in the F11 Long Jump Finals at the Paralympic Games in London 2012. Performances were recorded using four high-speed cameras, and speeds were measured using a radar speed gun. The images were processed using validated image analysis software. Results The long jump run-up is shorter in blind athletes than in sighted athletes. We observed statistically significant differences for body centre of mass velocity and an increase in speed over the last three strides prior to take-off, contrasting with reports for sighted athletes and athletes with less severe visual impairment, who maintain or reduce their speed during the last stride. Stride length for the last three strides was the only spatial characteristic that was not significantly associated with effective jump distance. Blind long jumpers extend rather than shorten their last stride. Contact time with the take-off board is longer than that reported for sighted athletes. Conclusion The actions of blind long jumpers, unlike those without disabilities, do not vary their leg actions during the final runway approach for optimal placement on the take-off board

Next-Generation Crispr Gene-Drive Systems Using Cas12A Nuclease

One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. to address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests