Evaluation of the Beam Coupling Impedance of New Beam Screen Designs for the LHC Injection Kicker Magnets

During the 2011 run of the LHC there was a significant measured temperature increase in the LHC Injection Kicker Magnets (MKI) during operation with 50ns bunch spacing. This was due to increased beam-induced heating of the magnet due to beam impedance. Due to concerns about future heating with the increased total intensity to nominal and ultimate luminosities a review of the impedance reduction techniques within the magnet was required. A number of new beam screen designs are proposed and their impedance evaluated. Heating estimates are also given with a particular attention paid to future intensity upgrades to ultimate parameters

Application of Magnetic Markers for Precise Measurement of Magnetic Fields in Ramped Accelerators

For precise measurements of the magnetic field in ramped machines, different magnetic markers are in use. The best known are peaking strips, Nuclear Magnetic Resonance (NMR) probes and Electron Spin Resonance (ESR) probes. Their operational principles and limitations are explained and some examples of recent and new applications are given. A fuller theoretical description is given of the lesser-known Ferrimagnetic Resonance (FMR) probe and its practical application. The essential purpose of these magnetic markers is the in situ calibration of either on-line magnetic field measurements (e.g. via a magnetic pick-up coil) or field predictions (e.g. using a magnet model)

Coaxial Wire Measurements of Ferrite Kicker Magnets

Fast kicker magnets are used to inject beam into and eject beam out of the CERN accelerator rings. These kickers are generally transmission line type magnets with a rectangular shaped aperture through which the beam passes. Unless special precautions are taken the impedance of the yoke can provoke significant beam induced heating, especially for high intensities. In addition the impedance may contribute to beam instabilities. The results of longitudinal and transverse impedance measurements, for various kicker magnets, are presented and compared with analytical calculations: in addition predictions from a numerical analysis are discussed

Investigations Of Salvinorin A: Synthetic Isolation, Quantification, And In Vivo Characteristics

While many ligands are known to interact with the opioid receptor system, most can be traced back to the common morphine scaffold. In several cases ligands have been developed that are selective for either the mu, kappa, or delta opioid receptors. Selective kappa opioid receptor agonists and antagonists have shown potential to be used to decrease cocaine self-administration and be utilized in the treatment of relapse. The emergence of salvinorin A as a novel scaffold, that selectively interacts with the kappa opioid receptor, retains therapeutic potential with a reduced side effect profile to the current treatments. Traditional mu opioid ligands, such as morphine, have life threatening side effects such as respiratory depression and constipation among other drawbacks like tolerance and dependence. To fully investigate the potential of salvinorin A as a viable alternative for therapeutic treatment it must be isolated in high purity for pharmacological evaluation. In efforts to isolate high purity salvinorin A, a reactive handle was generated that was shown to undergo cycloaddition to the furan ring of salvinorin A. This handle was developed using the reactivity limitations that were also investigated for the Diels-Alder cycloaddition of electron deficient alkenes and alkynes with the salvinorin A furan ring. In order to understand the unique mode of interaction salvinorin A imparts on the opioid receptor system, investigations into the pharmacological profile of salvinorin A were explored. Analytical methods were developed for the identification and quantification of salvinorin A from non-human primate cerebrospinal fluid and human plasma. This method was then exploited to develop a time-course graph for the measurement of in vivo concentrations of salvinorin A in various biological fluids which could be correlated to subjective and biological observations

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Bats, Bacteria, and Bat Smell V.2.0: Repeatable Sex-Specific Differences in Scent Organ Microbiota

Reproducibility is a fundamental principle in science, ensuring reliable and valid findings. However, replication studies are scarce, particularly in ecology, due to the emphasis on novelty for publication. We explored the possibility of replicating original findings in the field of microbial and chemical ecology by conducting a conceptual replication of a previous study analysing the sex-specific differences in the microbial communities inhabiting the wing sacs, a scent organ with crucial functions in olfactory communication, of greater sac-winged bat (Saccopteryx bilineata). In the original study, the skin swabs from the antebrachial wing sacs of the males and wing sac rudiments of the females were analysed using culture-dependent methods to test sex-specific differences. The authors demonstrated that males have lower microbial richness and different microbial composition than females. We attempted to reproduce these findings using 16S rRNA sequencing, which offers improved accuracy in pinpointing microbial members than culture-dependent methods because of advanced statistical methods. Our study validated the original study’s findings: Males had a lower microbial richness, and the community composition differed between the sexes. Furthermore, in the current study, males had an increased abundance of bacteria that might potentially be involved in odour production and degradation of malodorous substances and antimicrobial production. Our conceptual replication study corroborated that microbes can play a role in shaping their host’s olfactory phenotype and consequently influence sexual selection. Furthermore, the current study emphasises the importance of replication efforts and hopefully encourages a culture that values replication studies in scientific practice

Discovery of a Novel Selective Kappa-Opioid Receptor Agonist Using Crystal Structure-Based Virtual Screening

Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for non-addictive opioid therapeutics and novel chemical tools to study physiological functions regulated by the KOP receptor, we screened in silico its recently released inactive crystal structure. A selective novel KOP receptor agonist emerged as a notable result, and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain

The 2015 Annual Meeting of SETAC German Language Branch in Zurich (7-10 September, 2015): ecotoxicology and environmental chemistry-from research to application

This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1

Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A

As part of our continuing efforts toward more fully understanding the structure−activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels−Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure−activity relationships of furan-containing natural products

Possible Missing Sources of Atmospheric Glyoxal Part II: Oxidation of Toluene Derived from the Primary Production of Marine Microorganisms.

BACKGROUND: Glyoxal has been implicated as a significant contributor to the formation of secondary organic aerosols, which play a key role in our ability to estimate the impact of aerosols on climate. Elevated concentrations of glyoxal over open ocean waters suggest that there exists an additional source, different from urban and forest environments, which has yet to be identified. METHODS: Based on mass spectrometric analyses of nascent sea spray aerosols (SSAs) and gas-phase molecules generated during the course of a controlled algal bloom, the work herein suggests that marine microorganisms are capable of excreting toluene in response to environmental stimuli. Additional culture flask experiments demonstrated that pathogenic attack could also serve as a trigger for toluene formation. Using solid-phase microextraction methods, the comparison of samples collected up-channel and over the breaking wave suggests it was transferred across the air-water interface primarily through SSA formation. RESULTS: The presence and then absence of phenylacetic acid in the SSA days prior to the appearance of toluene support previous reports that proposed toluene is produced as a metabolite of phenylalanine through the Shikimate pathway. As a result, once in the atmosphere, toluene is susceptible to oxidation and subsequent degradation into glyoxal. CONCLUSIONS: This work adds to a minimal collection of literature that addresses the primary production of aromatic hydrocarbons from marine microorganisms and provides a potential missing source of glyoxal that should be considered when accounting for its origins in remote ocean regions