Bi-spectral beam extraction in combination with a focusing feeder

Bi-spectral beam extraction combines neutrons from two different kind of moderators into one beamline, expanding the spectral range and thereby the utilization of an instrument. This idea can be realized by a mirror that reflects long wavelength neutrons from an off-axis colder moderator into a neutron guide aligned with another moderator emitting neutrons with shorter wavelengths which will be transmitted through the mirror. The mirror used in such systems is typically several meters long, which is a severe disadvantage because it reduces the possible length of a focusing device in design concepts requiring a narrow beam at a short distance from the source, as used in many instruments under development for the planned European Spallation Source (ESS). We propose a shortened extraction system consisting of several mirrors, and show that such an extraction system is better suited for combination with a feeder in an eye of the needle design, illustrated here in the context of a possible ESS imaging beamline.Comment: Published in Nuclear Instruments and Methods in Physics Research, Section

Design of a horizontal neutron reflectometer for the European Spallation Source

A design study of a horizontal neutron reflectometer adapted to the general baseline of the long pulse European Spallation Source (ESS) is presented. The instrument layout comprises solutions for the neutron guide, high-resolution pulse shaping and beam bending onto a sample surface being so far unique in the field of reflectometry. The length of this instrument is roughly 55 m, enabling $\delta \lambda / \lambda$ resolutions from 0.5% to 10%. The incident beam is focussed in horizontal plane to boost measurements of sample sizes of 1*1 cm{^2} and smaller with potential beam deflection in both downward and upward direction. The range of neutron wavelengths untilized by the instrument is 2 to 7.1 (12.2, ...) {\AA}, if every (second, ...) neutron source ulse is used. Angles of incidence can be set between 0{\deg} and 9{\deg} with a total accessible q-range from 4*10^{-3} {\AA}^{-1} up to 1 {\AA}^{-1}. The instrument operates both in {\theta}/{\theta} (free liquid surfaces) and {\theta}/2{\theta} (solid/liquid, air/solid interfaces) geometry. The experimental setup will in particular enable direct studies on ultrathin films (d ~ 10 {\AA}) and buried monolayers to multilayered structures of up to 3000 {\AA} total thickness. The horizontal reflectometer will further foster investigations of hierarchical systems from nanometer to micrometer length scale, as well as their kinetics and dynamical properties, in particular under load (shear, pressure, external fields). Polarization and polarization analysis as well as the GISANS option are designed as potential modules to be implemented separately in the generic instrument layout. The instrument is highly flexible and offers a variety of different measurement modes. With respect to its mechanical components the instrument is exclusively based on current technology. Risks of failure for the chosen setup are minimum.Comment: Matched to the version submitted to Nuclear Instruments and Methods

Identification of epidermal Pdx1 expression discloses different roles of Notch1 and Notch2 in murine KrasG12D-induced skin carcinogenesis in vivo

Background The Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis. To study the role of Notch and oncogenic Kras signaling in a progenitor cell population, Pdx1-Cre mice were utilized to generate conditional oncogenic KrasG12D mice with ablation of Notch1 and/or Notch2. Methodology/Principal Findings Surprisingly, mice with activated KrasG12D and Notch1 but not Notch2 ablation developed skin papillomas progressing to squamous cell carcinoma providing evidence for Pdx1 expression in the skin. Immunostaining and lineage tracing experiments indicate that PDX1 is present predominantly in the suprabasal layers of the epidermis and rarely in the basal layer. Further analysis of keratinocytes in vitro revealed differentiation-dependent expression of PDX1 in terminally differentiated keratinocytes. PDX1 expression was also increased during wound healing. Further analysis revealed that loss of Notch1 but not Notch2 is critical for skin tumor development. Reasons for this include distinct Notch expression with Notch1 in all layers and Notch2 in the suprabasal layer as well as distinctive p21 and β-catenin signaling inhibition capabilities. Conclusions/Significance Our results provide strong evidence for epidermal expression of Pdx1 as of yet not identified function. In addition, this finding may be relevant for research using Pdx1-Cre transgenic strains. Additionally, our study confirms distinctive expression and functions of Notch1 and Notch2 in the skin supporting the importance of careful dissection of the contribution of individual Notch receptors

Algebroid Yang-Mills Theories

A framework for constructing new kinds of gauge theories is suggested. Essentially it consists in replacing Lie algebras by Lie or Courant algebroids. Besides presenting novel topological theories defined in arbitrary spacetime dimensions, we show that equipping Lie algebroids E with a fiber metric having sufficiently many E-Killing vectors leads to an astonishingly mild deformation of ordinary Yang-Mills theories: Additional fields turn out to carry no propagating modes. Instead they serve as moduli parameters gluing together in part different Yang-Mills theories. This leads to a symmetry enhancement at critical points of these fields, as is also typical for String effective field theories.Comment: 4 pages; v3: Minor rewording of v1, version to appear in Phys. Rev. Let

Transition from accelerated to decelerated regimes in JT and CGHS cosmologies

In this work we discuss the possibility of positive-acceleration regimes, and their transition to decelerated regimes, in two-dimensional (2D) cosmological models. We use general relativity and the thermodynamics in a 2D space-time, where the gas is seen as the sources of the gravitational field. An early-Universe model is analyzed where the state equation of van der Waals is used, replacing the usual barotropic equation. We show that this substitution permits the simulation of a period of inflation, followed by a negative-acceleration era. The dynamical behavior of the system follows from the solution of the Jackiw-Teitelboim equations (JT equations) and the energy-momentum conservation laws. In a second stage we focus the Callan-Giddings-Harvey-Strominger model (CGHS model); here the transition from the inflationary period to the decelerated period is also present between the solutions, although this result depend strongly on the initial conditions used for the dilaton field. The temporal evolution of the cosmic scale function, its acceleration, the energy density and the hydrostatic pressure are the physical quantities obtained in through the analysis.Comment: To appear in Europhysics Letter

The behaviour of random forest permutation-based variable importance measures under predictor correlation

<p>Abstract</p> <p>Background</p> <p>Random forests (RF) have been increasingly used in applications such as genome-wide association and microarray studies where predictor correlation is frequently observed. Recent works on permutation-based variable importance measures (VIMs) used in RF have come to apparently contradictory conclusions. We present an extended simulation study to synthesize results.</p> <p>Results</p> <p>In the case when both predictor correlation was present and predictors were associated with the outcome (H_A), the unconditional RF VIM attributed a higher share of importance to correlated predictors, while under the null hypothesis that no predictors are associated with the outcome (H₀) the unconditional RF VIM was unbiased. Conditional VIMs showed a decrease in VIM values for correlated predictors versus the unconditional VIMs under H_Aand was unbiased under H₀. Scaled VIMs were clearly biased under H_Aand H₀.</p> <p>Conclusions</p> <p>Unconditional unscaled VIMs are a computationally tractable choice for large datasets and are unbiased under the null hypothesis. Whether the observed increased VIMs for correlated predictors may be considered a "bias" - because they do not directly reflect the coefficients in the generating model - or if it is a beneficial attribute of these VIMs is dependent on the application. For example, in genetic association studies, where correlation between markers may help to localize the functionally relevant variant, the increased importance of correlated predictors may be an advantage. On the other hand, we show examples where this increased importance may result in spurious signals.</p

Exploring nucleic acid condensation and release from individual parvovirus particles with different physicochemical cues

In the infection cycle, viruses release their genome in the host cell during uncoating. Here we use a variety of physicochemical procedures to induce and monitor the in vitro uncoating of ssDNA from individual Minute Virus of Mice (MVM) particles. Our experiments revealed two pathways of genome release: i) filamentous ssDNA appearing around intact virus particles when using gradual mechanical fatigue and heating at moderate temperature (50 °C). ii) thick structures of condensed ssDNA appearing when the virus particle is disrupted by mechanical nanoindentations, denaturing agent guanidinium chloride and high temperature (70 °C). We propose that in the case of filamentous ssDNA, when the capsid integrity is conserved, the genome is externalized through one channel of the capsid pores. However, the disruption of virus particles revealed a native structure of condensed genome. The mechanical analysis of intact particles after DNA strands ejection confirm the stabilization role of ssDNA in MV

Generalized 2d dilaton gravity with matter fields

We extend the classical integrability of the CGHS model of 2d dilaton gravity [1] to a larger class of models, allowing the gravitational part of the action to depend more generally on the dilaton field and, simultaneously, adding fermion- and U(1)-gauge-fields to the scalar matter. On the other hand we provide the complete solution of the most general dilaton-dependent 2d gravity action coupled to chiral fermions. The latter analysis is generalized to a chiral fermion multiplet with a non-abelian gauge symmetry as well as to the (anti-)self-dual sector df = *df (df = -*df) of a scalar field f.Comment: 37 pages, Latex; typos and Eqs. (44,45) corrected; paragraph on p. 26, referring to a work of S. Solodukhin, reformulated; references adde

Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. METHODS: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. DISCUSSION: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS