Antileishmanial High-Throughput Drug Screening Reveals Drug Candidates with New Scaffolds

Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline

QUBIC instrument for CMB polarization measurements

Measurements of cosmic microwave background (CMB) polarization may reveal the presence of a background of gravitational waves produced during cosmic inflation, providing thus a test of inflationary models. The Q&U Bolometric Interferometer for Cosmology (QUBIC) is an experiment designed to measure the CMB polarization. It is based on the novel concept of bolometric interferometry, which combines the sensitivity of bolometric detectors with the properties of beam synthesis and control of calibration offered by interferometers. To modulate and extract the input polarized signal of the CMB, QUBIC exploits Stokes polarimetry based on a rotating half-wave plate (HWP). In this work, we illustrate the design of the QUBIC instrument, focusing on the polarization modulation system, and we present preliminary results of beam calibrations and the performance of the HWP rotator at 300 K

QUBIC VI: cryogenic half wave plate rotator, design and performances

Inflation Gravity Waves B-Modes polarization detection is the ultimate goal of modern large angular scale cosmic microwave background (CMB) experiments around the world. A big effort is undergoing with the deployment of many ground-based, balloon-borne and satellite experiments using different methods to separate this faint polarized component from the incoming radiation. One of the largely used technique is the Stokes Polarimetry that uses a rotating half-wave plate (HWP) and a linear polarizer to separate and modulate the polarization components with low residual cross-polarization. This paper describes the QUBIC Stokes Polarimeter highlighting its design features and its performances. A common systematic with these devices is the generation of large spurious signals synchronous with the rotation and proportional to the emissivity of the optical elements. A key feature of the QUBIC Stokes Polarimeter is to operate at cryogenic temperature in order to minimize this unwanted component. Moving efficiently this large optical element at low temperature constitutes a big engineering challenge in order to reduce friction power dissipation. Big attention has been given during the designing phase to minimize the differential thermal contractions between parts. The rotation is driven by a stepper motor placed outside the cryostat to avoid thermal load dissipation at cryogenic temperature. The tests and the results presented in this work show that the QUBIC polarimeter can easily achieve a precision below 0.1{\deg} in positioning simply using the stepper motor precision and the optical absolute encoder. The rotation induces only few mK of extra power load on the second cryogenic stage (~ 8 K).Comment: Part of a series of 8 papers on QUBIC to be submitted to a special issue of JCA

Simulations and performance of the QUBIC optical beam combiner

QUBIC, the Q & U Bolometric Interferometer for Cosmology, is a novel ground-based instrument that aims to measure the extremely faint B-mode polarisation anisotropy of the cosmic microwave background at intermediate angular scales (multipoles o

Traité élémentaire des chemins de fer

En Espasa t. XLIII, aparecen como fecha de publicación de la obra completa 1855-185