Total Syntheses of Amphidinolide H and G

Eureka! The first conquest of the exceptionally potent cytotoxic agent amphidinolide H, which exhibits activity in the picomolar range against human epidermoid cancer cells, was long overdue. The successful route critically hinges upon the scrupulous optimization of the fragment-coupling events (see picture; RCM=ring-closing metathesis) and on the careful adjustment of the peripheral protecting-group pattern

CARIOQA: Definition of a Quantum Pathfinder Mission

A strong potential gain for space applications is expected from the anticipated performances of inertial sensors based on cold atom interferometry (CAI) that measure the acceleration of freely falling independent atoms by manipulating them with laser light. In this context, CNES and its partners initiated a phase 0 study, called CARIOQA, in order to develop a Quantum Pathfinder Mission unlocking key features of atom interferometry for space and paving the way for future ambitious space missions utilizing this technology. As a cornerstone for the implementation of quantum sensors in space, the CARIOQA phase 0 aimed at defining the Quantum Pathfinder Mission's scenario and associated performance objectives. To comply with these objectives, the payload architecture has been designed to achieve long interrogation time and active rotation compensation on a BEC-based atom interferometer. A study of the satellite architecture, including all the subsystems, has been conducted. Several technical solutions for propulsion and attitude control have been investigated in order to guarantee optimal operating conditions (limitation of micro-vibrations, maximization of measurement time). A preliminary design of the satellite platform was performed.Comment: Proceedings of International Conference on Space Optics (ICSO) 2022; 3-7 October 2022; Dubrovnik; Croati

Tunneling control and localization for Bose-Einstein condensates in a frequency modulated optical lattice

The similarity between matter waves in periodic potential and solid-state physics processes has triggered the interest in quantum simulation using Bose-Fermi ultracold gases in optical lattices. The present work evidences the similarity between electrons moving under the application of oscillating electromagnetic fields and matter waves experiencing an optical lattice modulated by a frequency difference, equivalent to a spatially shaken periodic potential. We demonstrate that the tunneling properties of a Bose-Einstein condensate in shaken periodic potentials can be precisely controlled. We take additional crucial steps towards future applications of this method by proving that the strong shaking of the optical lattice preserves the coherence of the matter wavefunction and that the shaking parameters can be changed adiabatically, even in the presence of interactions. We induce reversibly the quantum phase transition to the Mott insulator in a driven periodic potential.Comment: Laser Physics (in press

Complex lithium ion dynamics in simulated LiPO3 glass studied by means of multi-time correlation functions

Molecular dynamics simulations are performed to study the lithium jumps in LiPO3 glass. In particular, we calculate higher-order correlation functions that probe the positions of single lithium ions at several times. Three-time correlation functions show that the non-exponential relaxation of the lithium ions results from both correlated back-and-forth jumps and the existence of dynamical heterogeneities, i.e., the presence of a broad distribution of jump rates. A quantitative analysis yields that the contribution of the dynamical heterogeneities to the non-exponential depopulation of the lithium sites increases upon cooling. Further, correlated back-and-forth jumps between neighboring sites are observed for the fast ions of the distribution, but not for the slow ions and, hence, the back-jump probability depends on the dynamical state. Four-time correlation functions indicate that an exchange between fast and slow ions takes place on the timescale of the jumps themselves, i.e., the dynamical heterogeneities are short-lived. Hence, sites featuring fast and slow lithium dynamics, respectively, are intimately mixed. In addition, a backward correlation beyond the first neighbor shell for highly mobile ions and the presence of long-range dynamical heterogeneities suggest that fast ion migration occurs along preferential pathways in the glassy matrix. In the melt, we find no evidence for correlated back-and-forth motions and dynamical heterogeneities on the length scale of the next-neighbor distance.Comment: 12 pages, 13 figure

J Clin Med

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children's stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQL(TM) and the Quality of Life Pediatric Inventory 4.0-PedsQL(TM). Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, "Heart Burn Reflux", "Nausea and Vomiting", and "Gas and Bloating"). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

ELGAR - A European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of 3.3 x 10 [hoch]-20 / [Wurzel] Hz at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology