DARC : Data Anonymization and Re-identification Challenge

National audienc

Strongly aligned gas-phase molecules at Free-Electron Lasers

We demonstrate a novel experimental implementation to strongly align molecules at full repetition rates of free-electron lasers. We utilized the available in-house laser system at the coherent x-ray imaging beamline at the Linac Coherent Light Source. Chirped laser pulses, i. e., the direct output from the regenerative amplifier of the Ti:Sa chirped pulse amplification laser system, were used to strongly align 2,5-diiodothiophene molecules in a molecular beam. The alignment laser pulses had pulse energies of a few mJ and a pulse duration of 94 ps. A degree of alignment of \left = 0.85 was measured, limited by the intrinsic temperature of the molecular beam rather than by the available laser system. With the general availability of synchronized chirped-pulse-amplified near-infrared laser systems at short-wavelength laser facilities, our approach allows for the universal preparation of molecules tightly fixed in space for experiments with x-ray pulses.Comment: 10 pages, 5 figure

Brain alterations associated with overweight evaluated by body mass index or body fat index in an elderly population: the PROOF study

Background/objectivesObesity is a complex health issue in which the brain plays a role yet to be determined, especially in the elderly. Indeed, in the ageing population, the balance between fat and lean mass is different; thus, the co-influence between the brain and obesity may differ between the elderly and younger subjects. Our main goal is thus to explore the relationship between the brain and obesity using two different approaches to measure obesity: body mass index (BMI) and an index centred on fat mass, the body fat index (BFI).Subjects/methodsAmong the 1,011 subjects of the PROOF population, 273 subjects aged 75 years underwent 3D magnetic resonance imaging as well as dual-energy X-ray absorptiometry to assess fat mass. Voxel-based morphometry was used to explore the local differences in brain volume with obesity.ResultsHigher BMI and BFI were associated with higher grey matter (GM) volume in the left cerebellum. Higher BMI and BFI were mainly associated with higher white matter volume in the left and right cerebellum and near the right medial orbital gyrus. Higher BMI was also associated with higher GM volume in the brainstem, whereas higher BFI was associated with higher GM volume in the left middle temporal gyrus. No decrease in white matter was associated with BMI or BFI.ConclusionIn the elderly, the relationship between the brain and obesity does not depend on the marker of obesity. Supra-tentorial brain structures seem to be slightly associated with obesity, whereas the cerebellum seems to be one of the key structures related to obesity

Resolving Length Scale Dependent Transient Disorder Through an Ultrafast Phase Transition

Material functionality can be strongly determined by structure extending only over nanoscale distances. The pair distribution function presents an opportunity to shift structural studies beyond idealized crystal models and investigate structure over varying length scales. Applying this method with ultrafast time resolution has the potential to similarly disrupt the study of structural dynamics and phase transitions. Here, we demonstrate such a measurement of CuIr$_{2}$S$_{4}$ optically pumped from its low temperature Ir-dimerized phase. Dimers are optically removed without spatial correlation, generating a structure whose level of disorder depends strongly on length scale. The re-development of structural ordering over tens of picoseconds is directly tracked over both space and time as a non-equilibrium state is approached. This measurement demonstrates both the crucial role of local structure and disorder in non-equilibrium processes and the feasibility of accessing this information with state-of-the-art XFEL facilities.Comment: 14 page manuscript with 5 figures. 6 page Supplementary with 8 figures. 20 pages and 11 figures in tota

Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules:Synthesis, electrochemical and SAR study

International audienceTo study the antiparasitic 8-nitroquinolin-2(1H)-one pharmacophore, a series of 31 derivatives was synthesized in 1-5 steps and evaluated in vitro against both Leishmania infantum and Trypanosoma brucei brucei. In parallel, the reduction potential of all molecules was measured by cyclic voltammetry. Structure-activity relationships first indicated that antileishmanial activity depends on an intramolecular hydrogen bond (described by X-ray diffraction) between the lactam function and the nitro group, which is responsible for an important shift of the redox potential (+0.3 V in comparison with 8-nitroquinoline). With the assistance of computational chemistry, a set of derivatives presenting a large range of redox potentials (from -1.1 to -0.45 V) was designed and provided a list of suitable molecules to be synthesized and tested. This approach highlighted that, in this series, only substrates with a redox potential above -0.6 V display activity toward L. infantum. Nevertheless, such relation between redox potentials and in vitro antiparasitic activities was not observed in T. b. brucei. Compound 22 is a new hit compound in the series, displaying both antileishmanial and antitrypanosomal activity along with a low cytotoxicity on the human HepG2 cell line. Compound 22 is selectively bioactivated by the type 1 nitroreductases (NTR1) of L. donovani and T. brucei brucei. Moreover, despite being mutagenic in the Ames test, as most of nitroaromatic derivatives, compound 22 was not genotoxic in the comet assay. Preliminary in vitro pharmacokinetic parameters were finally determined and pointed out a good in vitro microsomal stability (half-life > 40 min) and a 92% binding to human albumin