N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-β-lactamases (MBLs) and the virulence factor LasB from Pseudomonas aeruginosa

Increasing antimicrobial resistance is evolving to be one of the major threats to public health. To reduce the selection pressure and thus to avoid a fast development of resistance, novel approaches aim to target bacterial virulence instead of growth. Another strategy is to restore the activity of antibiotics already in clinical use. This can be achieved by the inhibition of resistance factors such as metallo-β-lactamases (MBLs). Since MBLs can cleave almost all β-lactam antibiotics, including the “last resort” carbapenems, their inhibition is of utmost importance. Here, we report on the synthesis and in vitro evaluation of N-aryl mercaptoacetamides as inhibitors of both clinically relevant MBLs and the virulence factor LasB from Pseudomonas aeruginosa. All tested N-aryl mercaptoacetamides showed low micromolar to submicromolar activities on the tested enzymes IMP-7, NDM-1 and VIM-1. The two most promising compounds were further examined in NDM-1 expressing Klebsiella pneumoniae isolates, where they restored the full activity of imipenem. Together with their LasB-inhibitory activity in the micromolar range, this class of compounds can now serve as a starting point for a multi-target inhibitor approach against both bacterial resistance and virulence, which is unprecedented in antibacterial drug discovery

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation

Hunting keV sterile neutrinos with KATRIN: Building the first TRISTAN module

The KATRIN (Karlsruhe Tritium Neutrino) experiment investigates the energetic endpoint of the tritium beta-decay spectrum to determine the effective mass of the electron anti-neutrino. The collaboration has reported a first mass measurement result at this TAUP-2019 conference. The TRISTAN project aims at detecting a keV-sterile neutrino signature by measuring the entire tritium beta-decay spectrum with an upgraded KATRIN system. One of the greatest challenges is to handle the high signal rates generated by the strong activity of the KATRIN tritium source while maintaining a good energy resolution. Therefore, a novel multi-pixel silicon drift detector and read-out system are being designed to handle rates of about 100 Mcps with an energy resolution better than 300 eV (FWHM). This report presents succinctly the KATRIN experiment, the TRISTAN project, then the results of the first 7-pixels prototype measurement campaign and finally describes the construction of the first TRISTAN module composed of 166 SDD-pixels as well as its implementation in KATRIN experiment

Characterization of silicon drift detectors with electrons for the TRISTAN project

Sterile neutrinos are a minimal extension of the standard model of particle physics. A promising model-independent way to search for sterile neutrinos is via high-precision β-spectroscopy. The Karlsruhe tritium neutrino (KATRIN) experiment, equipped with a novel multi-pixel silicon drift detector focal plane array and read-out system, named the TRISTAN detector, has the potential to supersede the sensitivity of previous laboratory-based searches. In this work we present the characterization of the first silicon drift detector prototypes with electrons and we investigate the impact of uncertainties of the detector\u27s response to electrons on the final sterile neutrino sensitivity

Characterization of Silicon Drift Detectors with Electrons for the TRISTAN Project

Sterile neutrinos are a minimal extension of the Standard Model of Particle Physics. A promising model-independent way to search for sterile neutrinos is via high-precision beta spectroscopy. The Karlsruhe Tritium Neutrino (KATRIN) experiment, equipped with a novel multi-pixel silicon drift detector focal plane array and read-out system, named the TRISTAN detector, has the potential to supersede the sensitivity of previous laboratory-based searches. In this work we present the characterization of the first silicon drift detector prototypes with electrons and we investigate the impact of uncertainties of the detector's response to electrons on the final sterile neutrino sensitivity.Comment: 18 pages, 8 figures. J. Phys. G: Nucl. Part. Phys. 48 01500