AWAKE: A Proton-Driven Plasma Wakefield Acceleration Experiment at CERN

The AWAKE Collaboration has been formed in order to demonstrate proton-driven plasma wakefield acceleration for the first time. This acceleration technique could lead to future colliders of high energy but of a much reduced length when compared to proposed linear accelerators. The CERN SPS proton beam in the CNGS facility will be injected into a 10 m plasma cell where the long proton bunches will be modulated into significantly shorter micro-bunches. These micro-bunches will then initiate a strong wakefield in the plasma with peak fields above 1 GV/m that will be harnessed to accelerate a bunch of electrons from about 20 MeV to the GeV scale within a few meters. The experimental program is based on detailed numerical simulations of beam and plasma interactions. The main accelerator components, the experimental area and infrastructure required as well as the plasma cell and the diagnostic equipment are discussed in detail. First protons to the experiment are expected at the end of 2016 and this will be followed by an initial three-four years experimental program. The experiment will inform future larger-scale tests of proton-driven plasma wakefield acceleration and applications to high energy colliders

The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme

Validating continuum lowering models via multi-wavelength measurements of integrated x-ray emission

X-ray emission spectroscopy is a well-established technique used to study continuum lowering in dense plasmas. It relies on accurate atomic physics models to robustly reproduce high-resolution emission spectra, and depends on our ability to identify spectroscopic signatures such as emission lines or ionization edges of individual charge states within the plasma. Here we describe a method that forgoes these requirements, enabling the validation of different continuum lowering models based solely on the total intensity of plasma emission in systems driven by narrow-bandwidth x-ray pulses across a range of wavelengths. The method is tested on published Al spectroscopy data and applied to the new case of solid-density partially-ionized Fe plasmas, where extracting ionization edges directly is precluded by the significant overlap of emission from a wide range of charge states

Inverse problem instabilities in large-scale modelling of matter in extreme conditions

Our understanding of physical systems often depends on our ability to match complex computational modeling with the measured experimental outcomes. However, simulations with large parameter spaces suffer from inverse problem instabilities, where similar simulated outputs can map back to very different sets of input parameters. While of fundamental importance, such instabilities are seldom resolved due to the intractably large number of simulations required to comprehensively explore parameter space. Here, we show how Bayesian inference can be used to address inverse problem instabilities in the interpretation of x-ray emission spectroscopy and inelastic x-ray scattering diagnostics. We find that the extraction of information from measurements on the basis of agreement with simulations alone is unreliable and leads to a significant underestimation of uncertainties. We describe how to statistically quantify the effect of unstable inverse models and describe an approach to experimental design that mitigates its impact

Inverse problem instabilities in large-scale modelling of matter in extreme conditions

Our understanding of physical systems often depends on our ability to match complex computational modeling with the measured experimental outcomes. However, simulations with large parameter spaces suffer from inverse problem instabilities, where similar simulated outputs can map back to very different sets of input parameters. While of fundamental importance, such instabilities are seldom resolved due to the intractably large number of simulations required to comprehensively explore parameter space. Here, we show how Bayesian inference can be used to address inverse problem instabilities in the interpretation of x-ray emission spectroscopy and inelastic x-ray scattering diagnostics. We find that the extraction of information from measurements on the basis of agreement with simulations alone is unreliable and leads to a significant underestimation of uncertainties. We describe how to statistically quantify the effect of unstable inverse models and describe an approach to experimental design that mitigates its impact

Etiology of upper eyelid retraction in thyroid eye disease

In this study upper eyelid retraction was evaluated in relation to lid lag. The significance of proptosis and limitation on upgaze was also investigated. It was observed that only moderate to severe limitation on upgaze enhanced the upper eyelid retraction. Proptosis did not correlate with upper eyelid retraction hut did correlate well with lower eyelid retraction. It was concluded that limitation on upgaze has some role in upper eyelid retraction whereas proptosis does not have a significant effect

Time-resolved XUV opacity measurements of warm-dense aluminium

The free-free opacity in plasmas is fundamental to our understanding of energy transport in stellar interiors and for inertial confinement fusion research. However, theoretical predictions in the challenging dense plasma regime are conflicting and there is a dearth of accurate experimental data to allow for direct model validation. Here we present time-resolved transmission measurements in solid-density Al heated by an XUV free-electron laser. We use a novel functional optimization approach to extract the temperature-dependent absorption coefficient directly from an oversampled pool of single-shot measurements, and find a pronounced enhancement of the opacity as the plasma is heated to temperatures of order of the Fermi energy. Plasma heating and opacity enhancement are observed on ultrafast timescales, within the duration of the femtosecond XUV pulse. We attribute further rises in the opacity on ps timescales to melt and the formation of warm dense matter