Faster chiral versus collinear magnetic order recovery after optical excitation revealed by femtosecond XUV scattering

While chiral spin structures stabilized by Dzyaloshinskii-Moriya interaction (DMI) are candidates as novel information carriers, their dynamics on the fs-ps timescale is little known. Since with the bulk Heisenberg exchange and the interfacial DMI two distinct exchange mechanisms are at play, the ultra-fast dynamics of the chiral order needs to be ascertained and compared to the dynamics of the conventional collinear order. Using an XUV free-electron laser we determine the fs-ps temporal evolution of the chiral order in domain walls in a magnetic thin film sample by an IR pump - X-ray magnetic scattering probe experiment. Upon demagnetisation we observe that the dichroic (CL-CR) signal connected with the chiral order correlator $m_z m_x$ in the domain walls recovers significantly faster than the (CL+CR) sum signal representing the average collinear domain magnetisation $m_z^2 + m_x^2$. We explore possible explanations based on spin structure dynamics and reduced transversal magnetisation fluctuations inside the domain walls and find that the latter can explain the experimental data leading to different dynamics for collinear magnetic order and chiral magnetic order.Comment: 28 pages, 14 figure

Generalized Brewster-Kerker effect in dielectric metasurfaces

Polarization is one of the key properties defining the state of light. It was discovered in the early 19th century by Brewster, among others, while studying light reflected from materials at different angles. These studies led to the first polarizers, based on Brewster's effect. One of the most active trends in photonics now is devoted to the study of miniaturized, sub-wavelength devices exhibiting similar, or even improved, functionalities compared to those achieved with bulk optical elements. In the present work, it is theoretically predicted that a properly designed all-dielectric metasurface exhibits a generalized Brewster effect potentially for any angle, wavelength and polarization of choice. The effect is experimentally demonstrated for an array of silicon nanodisks at visible wavelengths. The underlying physics of this effect can be understood in terms of the suppressed scattering at certain angles that results from the interference between the electric and magnetic dipole resonances excited in the nanoparticles, predicted by Kerker in early 80s. This reveals deep connection of Kerker's and Brewster's legacies and opens doors for Brewster phenomenon to new applications in photonics, which are not bonded to a specific polarization or angle of incidence.Comment: 12 pages, 5 figures, and supplementary information (22 pages

Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice

RNA alternative splicing (AS) expands the regulatory potential of eukaryotic genomes. The mechanisms regulating liver-specific AS profiles and their contribution to liver function are poorly understood. Here, we identify a key role for the splicing factor RNA-binding Fox protein 2 (RBFOX2) in maintaining cholesterol homeostasis in a lipogenic environment in the liver. Using enhanced individual-nucleotide-resolution ultra-violet cross-linking and immunoprecipitation, we identify physiologically relevant targets of RBFOX2 in mouse liver, including the scavenger receptor class B type I (Scarb1). RBFOX2 function is decreased in the liver in diet-induced obesity, causing a Scarb1 isoform switch and alteration of hepatocyte lipid homeostasis. Our findings demonstrate that specific AS programmes actively maintain liver physiology, and underlie the lipotoxic effects of obesogenic diets when dysregulated. Splice-switching oligonucleotides targeting this network alleviate obesity-induced inflammation in the liver and promote an anti-atherogenic lipoprotein profile in the blood, underscoring the potential of isoform-specific RNA therapeutics for treating metabolism-associated diseases

A global database for metacommunity ecology, integrating species, traits, environment and space

The use of functional information in the form of species traits plays an important role in explaining biodiversity patterns and responses to environmental changes. Although relationships between species composition, their traits, and the environment have been extensively studied on a case-by-case basis, results are variable, and it remains unclear how generalizable these relationships are across ecosystems, taxa and spatial scales. To address this gap, we collated 80 datasets from trait-based studies into a global database for metaCommunity Ecology: Species, Traits, Environment and Space; “CESTES”. Each dataset includes four matrices: species community abundances or presences/absences across multiple sites, species trait information, environmental variables and spatial coordinates of the sampling sites. The CESTES database is a live database: it will be maintained and expanded in the future as new datasets become available. By its harmonized structure, and the diversity of ecosystem types, taxonomic groups, and spatial scales it covers, the CESTES database provides an important opportunity for synthetic trait-based research in community ecology

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Structures topologiques de spin dans des couches minces d’alliages ferrimagnétiques

In these times of ecological concerns, the impact of our lifestyles on our environment is essential to analyze. Since energy is the main source of greenhouse gas emissions in the world, it is necessary to look for other ways to reduce our consumption.One of the major sources of energy consumption is data storage, with storage increasing significantly each year. A new technological solution has been proposed allowing the storage of these data at a lower energy cost and in a more efficient way by using magnetic skyrmions instead of magnetic domains. A magnetic skyrmion is a quasi-particle of size that can goes down to few atoms while a magnetic domain is of the order of a micrometer. Therefore, it is possible to imagine a data storage system based on the absence or the presence of this quasi-particle, representing the "0" or the "1" of a data bit. Thus, this thesis will focus on the nucleation and manipulation of magnetic skyrmions.These quasi-particles have been stabilized in various materials at room temperature, a condition for the use by all. The ability to nucleate, annihilate, and even move them using electric currents has also been shown. Nevertheless, the displacement of these magnetic structures generates several problems. Firstly, these structures seem to be particularly affected by structural defects in matter, the so-called "pinning". Indeed, magnetic skyrmions are so small that they can be trapped or even destroyed when passing through a defect in the material from which they come. Secondly, it appeared that the skyrmions did not move in linearly with the applied current but possess a perpendicular component causing them to deviate from the path of the electrons, an effect known as the "skyrmion Hall angle". This can be a problem as they may encounter the wall of a lithographed structure causing the non-homogeneity of the dynamics and implying a possible loss of the stored information. The use of a ferrimagnetic material has been proposed to solve partially these problems. Theoretically, it is possible to annihilate this "skyrmion Hall angle" in a ferrimagnetic material having a very weak magnetization at a very precise temperature. Thus, the experiments carried out in this thesis aim to nucleate magnetic skyrmions in ferrimagnetic materials while studying their dynamics.In this thesis, the nucleation of spin structures in ferrimagnetic materials based on GdFeCo has been reported. The structures were mapped using a "SEMPA" microscope where the in-plane magnetic configuration was revealed indicating the chiral character of the quasi-particles. The precise measurement of the domain walls, domain that separates two opposite magnetic domains in direction, also made it possible to deduct the value of the exchange constant, an important parameter in the physics of condensed matter but difficult to measure. Finally, it was highlighted the dynamics of magnetic skyrmions showing a deterministic character in CoDy alloys.En ces temps de préoccupations écologiques, l'impact de nos modes de vie sur notre environnement est essentiel à analyser. L'énergie étant la principale source d'émissions de gaz à effet de serre dans le monde, il est nécessaire de chercher des moyens pour réduire notre consommation. Une des sources importantes de consommation d'énergie est le stockage des données, stockage augmentant chaque année de manière significative. Il a été proposé une nouvelle solution technologique permettant le stockage de ces données à moindre coût énergétique et de manières plus efficace en utilisant des skyrmions magnétiques en lieu et place des domaines magnétiques. Un skyrmion magnétique est une quasi-particule magnétique de taille pouvant être réduite à quelques atomes alors qu'un domaine magnétique est de l'ordre du micromètre. Il est donc possible d'imaginer un système de stockage de l'information reposant sur l'absence ou la présence de cette quasi-particule, représentant le "0" ou le "1" d'un bit de donnée. Ainsi, cette thèse se focalisera sur la nucléation et la manipulation de skyrmions magnétiques. Ces quasi-particules ont récemment été stabilisé dans de divers matériaux à température ambiante, condition sine qua non à une utilisation par tous. Il a également été montré la possibilité de les nucléer, de les annihiler et même de les déplacer à l'aide de courants électriques. Néanmoins, le déplacement de ces structures magnétiques, à l'heure d'aujourd'hui pose problème. Premièrement, ces structures semblent être particulièrement affectées par les défauts structurels de la matière, ce qu'on appelle le "pinning". En effet, les skyrmions magnétiques sont si petits qu'ils peuvent être piégés voir détruits au passage d'un défaut dans le matériau d'où ils proviennent. Deuxièmement, il est apparu que les skyrmions ne se déplaçaient pas de manières linéaires avec le courant appliqué mais possédaient une composante perpendiculaire les faisant dévier du chemin des électrons, effet connu sous le nom de "skyrmion Hall angle". Ceci peut être un problème dans la mesure où ils peuvent rencontrer la paroi d'une structure lithographiée provoquant la non-homogénéité de la dynamique et impliquer une possible perte de l'information stockée. Pour remédier au moins en partie à ces problèmes, l'utilisation d'un matériau ferrimagnétique a été proposé. Théoriquement, il est possible d'annihiler ce "skyrmion Hall angle" dans un matériau ferrimagnétique possédant une très faible aimantation à une température bien précise. Ainsi, les expériences menées dans cette thèse ont pour but de nucléer des skyrmions magnétiques dans des matériaux ferrimagnétiques tout en étudiant leur dynamique. Dans cette thèse, la nucléation de structures de spin dans des matériaux ferrimagnétiques à base de GdFeCo a été relaté. Les structures ont été cartographié à l'aide d'un microscope "SEMPA" où la configuration magnétique dans le plan a été révélé, indiquant le caractère chiral des quasi-particules. La mesure précise des parois de domaines séparant deux domaines magnétiques opposés en direction a également permis de déduire la valeur de la constante d'échange, paramètre important dans la physique de la matière condensée mais difficile à mesurer. Enfin, il a été mis en évidence la dynamique de skyrmions magnétiques montrant un caractère déterministe dans des alliages de CoDy

Topological Spin Structures in Ferrimagnetic Thin Film Alloys

En ces temps de préoccupations écologiques, l'impact de nos modes de vie sur notre environnement est essentiel à analyser. L'énergie étant la principale source d'émissions de gaz à effet de serre dans le monde, il est nécessaire de chercher des moyens pour réduire notre consommation. Une des sources importantes de consommation d'énergie est le stockage des données, stockage augmentant chaque année de manière significative. Il a été proposé une nouvelle solution technologique permettant le stockage de ces données à moindre coût énergétique et de manières plus efficace en utilisant des skyrmions magnétiques en lieu et place des domaines magnétiques. Un skyrmion magnétique est une quasi-particule magnétique de taille pouvant être réduite à quelques atomes alors qu'un domaine magnétique est de l'ordre du micromètre. Il est donc possible d'imaginer un système de stockage de l'information reposant sur l'absence ou la présence de cette quasi-particule, représentant le "0" ou le "1" d'un bit de donnée. Ainsi, cette thèse se focalisera sur la nucléation et la manipulation de skyrmions magnétiques. Ces quasi-particules ont récemment été stabilisé dans de divers matériaux à température ambiante, condition sine qua non à une utilisation par tous. Il a également été montré la possibilité de les nucléer, de les annihiler et même de les déplacer à l'aide de courants électriques. Néanmoins, le déplacement de ces structures magnétiques, à l'heure d'aujourd'hui pose problème. Premièrement, ces structures semblent être particulièrement affectées par les défauts structurels de la matière, ce qu'on appelle le "pinning". En effet, les skyrmions magnétiques sont si petits qu'ils peuvent être piégés voir détruits au passage d'un défaut dans le matériau d'où ils proviennent. Deuxièmement, il est apparu que les skyrmions ne se déplaçaient pas de manières linéaires avec le courant appliqué mais possédaient une composante perpendiculaire les faisant dévier du chemin des électrons, effet connu sous le nom de "skyrmion Hall angle". Ceci peut être un problème dans la mesure où ils peuvent rencontrer la paroi d'une structure lithographiée provoquant la non-homogénéité de la dynamique et impliquer une possible perte de l'information stockée. Pour remédier au moins en partie à ces problèmes, l'utilisation d'un matériau ferrimagnétique a été proposé. Théoriquement, il est possible d'annihiler ce "skyrmion Hall angle" dans un matériau ferrimagnétique possédant une très faible aimantation à une température bien précise. Ainsi, les expériences menées dans cette thèse ont pour but de nucléer des skyrmions magnétiques dans des matériaux ferrimagnétiques tout en étudiant leur dynamique. Dans cette thèse, la nucléation de structures de spin dans des matériaux ferrimagnétiques à base de GdFeCo a été relaté. Les structures ont été cartographié à l'aide d'un microscope "SEMPA" où la configuration magnétique dans le plan a été révélé, indiquant le caractère chiral des quasi-particules. La mesure précise des parois de domaines séparant deux domaines magnétiques opposés en direction a également permis de déduire la valeur de la constante d'échange, paramètre important dans la physique de la matière condensée mais difficile à mesurer. Enfin, il a été mis en évidence la dynamique de skyrmions magnétiques montrant un caractère déterministe dans des alliages de CoDy.In these times of ecological concerns, the impact of our lifestyles on our environment is essential to analyze. Since energy is the main source of greenhouse gas emissions in the world, it is necessary to look for other ways to reduce our consumption.One of the major sources of energy consumption is data storage, with storage increasing significantly each year. A new technological solution has been proposed allowing the storage of these data at a lower energy cost and in a more efficient way by using magnetic skyrmions instead of magnetic domains. A magnetic skyrmion is a quasi-particle of size that can goes down to few atoms while a magnetic domain is of the order of a micrometer. Therefore, it is possible to imagine a data storage system based on the absence or the presence of this quasi-particle, representing the "0" or the "1" of a data bit. Thus, this thesis will focus on the nucleation and manipulation of magnetic skyrmions.These quasi-particles have been stabilized in various materials at room temperature, a condition for the use by all. The ability to nucleate, annihilate, and even move them using electric currents has also been shown. Nevertheless, the displacement of these magnetic structures generates several problems. Firstly, these structures seem to be particularly affected by structural defects in matter, the so-called "pinning". Indeed, magnetic skyrmions are so small that they can be trapped or even destroyed when passing through a defect in the material from which they come. Secondly, it appeared that the skyrmions did not move in linearly with the applied current but possess a perpendicular component causing them to deviate from the path of the electrons, an effect known as the "skyrmion Hall angle". This can be a problem as they may encounter the wall of a lithographed structure causing the non-homogeneity of the dynamics and implying a possible loss of the stored information. The use of a ferrimagnetic material has been proposed to solve partially these problems. Theoretically, it is possible to annihilate this "skyrmion Hall angle" in a ferrimagnetic material having a very weak magnetization at a very precise temperature. Thus, the experiments carried out in this thesis aim to nucleate magnetic skyrmions in ferrimagnetic materials while studying their dynamics.In this thesis, the nucleation of spin structures in ferrimagnetic materials based on GdFeCo has been reported. The structures were mapped using a "SEMPA" microscope where the in-plane magnetic configuration was revealed indicating the chiral character of the quasi-particles. The precise measurement of the domain walls, domain that separates two opposite magnetic domains in direction, also made it possible to deduct the value of the exchange constant, an important parameter in the physics of condensed matter but difficult to measure. Finally, it was highlighted the dynamics of magnetic skyrmions showing a deterministic character in CoDy alloys

A systematic review of predicted pathogenic PALB2 variants: an analysis of mutational overlap between epithelial cancers.

Partner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous DNA recombination. Germline loss-of-function variants in the PALB2 gene may confer an increased lifetime risk of breast, pancreatic, ovarian and other cancers. However, the complete spectrum of predicted pathogenic PALB2 variants associated with each tissue type of cancer remains unknown. A systematic review is performed with the aim of cataloguing predicted pathogenic PALB2 variants in breast, ovary and pancreas cancers. All catalogued predicted pathogenic variants are analysed to assess for overlap and mutational "hotspots" within gene exons. Our results showed that 911 (92.5%) cases were described in breast cancer patients, 49 (5.0%) cases were described in ovarian cancer patients, and 24 (2.4%) cases were described in pancreatic cancer patients. The top five most frequently reported predicted pathogenic PALB2 variants were c.509_510delGA, c.3113G > A, c.1592delT, c.172_175delTTGT, and c.1240C > T, accounting for 57.3% of all cases. Breast and pancreatic cancers share five variants while breast and ovarian cancers share 12 variants. Breast, ovarian and pancreatic cancers share eight common variants. Exons with the highest mutation rates were exons 2 (6.7%), 1 (6.3%) and 3 (5.8%). This systematic review provides a quantitative catalogue of predicted pathogenic PALB2 variants described in cancers. This comprehensive analysis of the PALB2 mutational spectrum represents a useful resource for clinicians overseeing PALB2-related cancer surveillance and provides a valuable resource for future PALB2-specific research