61 research outputs found

    Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif

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    Optimization of the sulfonamide-based kappa opioid receptor (KOR) antagonist probe molecule ML140 through constraint of the sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure-activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo tool to investigate the therapeutic potential of KOR antagonists

    Langevin equations for interacting fermions and Cooper-like pairing in trapped one-dimensional fermions

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    Momentum correlations in a one-dimensional equilibrium ensemble of trapped fermions, with a point interaction between particles of opposite spin have been studied. In the degenerate regime correlations were observed between fermions with opposite spins and momenta, similar to Cooper pairing. These correlations appear as soon as the temperature is below the Fermi energy, which is a much less stringent condition than that of the BCS transition proper. Calculations are carried out in both perturbative and non-perturbative regimes. To achieve the latter. it is shown that interacting fermionic dynamics may be solved as a stochastic linear transformation of Grassmann algebra generators, much in the way random c-number paths are introduced in the conventional quantum stochastics of bosons. Importantly, the method thus emerging is inherently free of the sign problem

    The design, construction, and commissioning of the KATRIN experiment

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    The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [1] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [2]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns
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