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International audience; We present the commissioning of the FAB10 beamline (Femtosecond to Attosecond Beamline at 10 kHz repetition rate) that has been developped and operated in the last few years at the ATTOLab facility of Paris-Saclay University. Based on the high harmonic generation process, the beamline is dedicated to investigations of ultrafast dynamics in a broad variety of systems ranging from gas phase to condensed matter in pump-probe arrangements. Its design and operation has been strongly influenced by both the laser and the large scale instruments communities, which makes it unique in several aspects. In particular, it is possible to tune the extreme ultraviolet (XUV, 10–100 eV) bandwidth from 0.2 to 20 eV – with corresponding pulse duration from 30 to 0.3 femtoseconds (fs) – thanks to an original and fully automated XUV spectral filter with three operation modes. After a general overview of the beamline features, each of those operation modes is described, characterized and illustrated with commissioning experiments.

Two-dimensional (2D) van der Waals (vdW) ferromagnetic metals FexGeTe2 with x = 3-5 have raised significant interest in the scientific community. Fe5GeTe2 shows prospects for spintronic applications since the Curie temperature Tc has been reported near or higher than 300 K. In the present work, epitaxial Fe5-dGeTe2 (FGT) heterostructures were grown by Molecular Beam Epitaxy (MBE) on insulating crystalline substrates. The FGT films were combined with Bi2Te3 topological insulator (TI) aiming to investigate the possible beneficial effect of the TI on the magnetic properties of FGT. FGT/Bi2Te3 films were compared to FGT capped only with AlOx to prevent oxidation. SQUID and MOKE measurements revealed that the growth of Bi2Te3 TI on FGT films significantly enhances the saturation magnetization of FGT as well as the Tc well above room temperature (RT) reaching record values of 570 K. First-principles calculations predict a shift of the Fermi level and an associated enhancement of the majority spin ( primarily) as well as the total density of states at the Fermi level suggesting that effective doping of FGT from Bi2Te3 could explain the enhancement of ferromagnetism in FGT. It is also predicted that strain induced stabilization of a high magnetic moment phase in FGT/Bi2Te3 could be an alternative explanation of magnetization and Tc enhancement. Ferromagnetic resonance measurements evidence an enhanced broadening in the FGT/ Bi2Te3 heterostructure when compared to FGT. We obtain a large spin mixing conductance of g"# eff = 4.4 x 1020 m-2, which demonstrates the great potential of FGT/Bi2Te3 systems for spin-charge conversion applications at room temperature.

KEAP1 mutations have been associated with reduced survival in lung adenocarcinoma (LUAD) patients treated with immune checkpoint inhibitors (ICIs), particularly in the presence of STK11/KRAS alterations. We hypothesized that, beyond co-occurring genomic events, clonality prediction may help identify deleterious KEAP1 mutations and their counterparts with retained sensitivity to ICIs.Beta-binomial modelling of sequencing read counts was used to infer KEAP1 clonal inactivation by combined somatic mutation and loss of heterozygosity (KEAP1 C-LOH) versus partial inactivation (KEAP1 clonal diploid-subclonal, KEAP1 CD-SC) in the MSK MetTropism cohort (N=2,550). Clonality/LOH prediction was compared to a streamlined clinical classifier that relies on variant allele frequencies (VAFs) and tumor purity (TP) (VAF/TP ratio). The impact of this classification on survival outcomes was tested in two independent cohorts of LUAD patients treated with immunotherapy (MSK/Rome N=237; DFCI N=461). Immune-related features were studied by exploiting RNA-sequencing data (TCGA) and multiplexed immunofluorescence (DFCI mIF cohort).Clonality/LOH inference in the MSK MetTropism cohort overlapped with a clinical classification model defined by the VAF/TP ratio. In the ICI-treated MSK/Rome discovery cohort, predicted KEAP1 C-LOH mutations were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAP1 wild-type cases (PFS log-rank P=0.001; OS log-rank P0.001). Similar results were obtained in the DFCI validation cohort (PFS log-rank P=0.006; OS log-rank P=0.014). In both cohorts, we did not observe any significant difference in survival outcomes when comparing KEAP1 CD-SC and wild-type tumors. Immune deconvolution and multiplexed immunofluorescence revealed that KEAP1 C-LOH and KEAP1 CD-SC differed for immune-related features.KEAP1 C-LOH mutations are associated with an immune-excluded phenotype and worse clinical outcomes among advanced LUAD patients treated with ICIs. By contrast, survival outcomes of patients whose tumors harbored KEAP1 CD-SC mutations were similar to those with KEAP1 wild-type LUADs.

Growing evidence report that non-genetic-driven events such as enhancer reprogramming promote neoplastic transformation and strongly contribute to the phenotypical heterogeneity of cancers as much as genetic variation. In this context, we investigated the role of enhancers in sustaining oncogenic transformation in B-Cell Acute Lymphoblastic leukemia in children (BCP-ALL), a type of cancer caused by the accumulation of lymphoid progenitor cells in the bone marrow and a leading cause of cancer-related mortality in children. Using next-generation sequencing (ATAC-seq), we built the most up-to-date map of chromatin accessibility in pediatric BCP-ALL. We observed that enhancer activity dynamically changes during cancer progression and represents principal phenomena underlying phenotypic–functional characteristics of BCP-ALL progression. BCP-ALL patients are dominated by a regulatory repertoire (N=∼11k) originally represented at diagnosis that shrinks under treatments and subsequently re-expands, driving the relapse. We then deployed a wide range of in-vivo, in-vitro assays, and in-silico analyses to demonstrate the impact of enhancer activity in determining the phenotypical complexity. CRISPR-Cas-9-mediated validation of selected productive enhancers demonstrated a high capability of these regions to control MYB and DCTD oncogenic activities. Taken together, these findings provide direct support to the notion that enhancer plasticity is a crucial determinant of the BCP-ALL phenotype.

Ion implantation provides a precise method of incorporating dopant atoms in semiconductors, provided lattice damage due to the implantation process can be annealed and the dopant atoms located on regular lattice sites. We have undertaken 57Fe emission Mössbauer spectroscopy measurements on GaAs and GaP single crystals following implantation of radioactive 57Mn + ions, to study the lattice sites of the implanted ions, the annealing of implantation induced damage and impurity-vacancy complexes formed. The Mössbauer spectra were analyzed with four spectral components: an asymmetric doublet (D1) attributed to Fe atoms in distorted environments due to implantation damage, two single lines, S1 assigned to Fe on substitutional Ga sites, and S2 to Fe on interstitial sites, and a low intensity symmetric doublet (D2) assigned to impurity-vacancy complexes. The variations in the extracted hyperfine parameters of D1 for both materials at high temperatures (T > 400 K) suggests changes in the immediate environment of the Fe impurity atoms and different bonding mechanism to the Mössbauer probe atom. The results show that the annealing of the radiation induced damage is more prominent in GaAs compared to GaP.

Variation in gene copy number is increasingly recognized as a common, heritable source of inter-individual differences in genomic sequence. The role of copy number variation is well established in the pathogenesis of rare genomic disorders. More recently, germline and somatic copy number variation have been shown to be important pathogenic factors in a range of common diseases, including infectious, autoimmune and neuropsychiatric diseases and cancer. In this review, we describe the range of methods available for measuring copy number variants (CNVs) in individuals and populations, including the limitations of presently available assays, and highlight some key examples of common diseases in which CNVs have been shown clearly to have a pathogenic role. Although there has been major progress in this field in the last 5 years, understanding the full contribution of CNVs to the genetic basis of common diseases will require further studies, with more accurate CNV assays and larger cohorts than have presently been completed.

Naturally occurring variation in gene copy number is increasingly recognized as a major source of inter-individual differences in phenotype and is an important susceptibility factor for genetically complex diseases. Several studies provide evidence of copy number variation at genes involved in inflammation and immunity highlighting their possible contribution to the inter-individual variation observed in immune responses. This review will explore copy number variation at the Fc gamma receptor cluster and its relevance in the pathogenesis of common human diseases.

The tumor suppressor p53 is mainly involved in the transcriptional regulation of a large number of growth-arrest- and apoptosisrelated genes. However, a clear understanding of which factor/s influences the choice between these two opposing p53-dependent outcomes remains largely elusive. We have previously described that in response to DNA damage, the RNA polymerase II-binding protein Che-1/AATF transcriptionally activates p53. Here, we show that Che-1 binds directly to p53. This interaction essentially occurs in the first hours of DNA damage, whereas it is lost when cells undergo apoptosis in response to posttranscriptional modifications. Moreover, Che-1 sits in a ternary complex with p53 and the oncosuppressor Brca1. Accordingly, our analysis of genome-wide chromatin occupancy by p53 revealed that p53/Che1 interaction results in preferential transactivation of growth arrest p53 target genes over its pro-apoptotic target genes. Notably, exposure of Che-1+/ − mice to ionizing radiations resulted in enhanced apoptosis of thymocytes, compared with WT mice. These results confirm Che-1 as an important regulator of p53 activity and suggest Che-1 to be a promising yet attractive drug target for cancer therapy.

The evolution of microstructure and phase structure of ultrathin HfO2 films on Si(100) under ultrahigh-vacuum annealing is investigated in situ by x-ray photoelectron spectroscopy (XPS) and low-energy ion scattering (LEIS). The onset temperature of degradation is found to depend on film thickness. It is established that, for HfO2 (4 nm)/SiO2 (1 nm)/Si(100) specimens, 5-min annealing at about 900°C causes silicon (LEIS evidence) to appear on the surface, the silicon being uncombined with oxygen or the metal (XPS evidence). A longer annealing at the same temperature produces HfSix; annealing at 950°C converts the entire HfO2 film into polycrystalline silicide whose grains are partly oriented as the Si substrate. With respect to annealing in a low-oxygen environment, the experimental results support a model whereby the degradation of an ultrathin HfO2 film starts with the formation of nanopores by clustering of oxygen vacancies, whose density increases sharply due to partial desorption of oxygen; HfOx with x < 2 then forms in the vicinity of vacancy clusters. It is concluded that the formation of hafnium silicide, the end product of HfO2 degradation, starts in Si surface areas at the bottom of nanopores.

Yttria sY2O3d is one of the candidate materials actively studied as a high dielectric constant replacement of amorphous silicon dioxide in downscaled microelectronic devices. An understanding of the physical properties of yttria epilayers on silicon is both a required prerequisite for applications and of fundamental interest. Using x-ray absorption spectroscopy at both the yttrium and oxygen K edges we study the local atomic and electronic structure in Y2O3 epilayers deposited on Sis001d. We find that above a thin near - interface layer the epilayers have a local atomic and electronic structure bearing a close similarity to that of bulk yttria; however, there is an increase in static disorder with decreasing thickness which can be correlated to an increase of the defectivity. The unoccupied electronic structure, as probed by near edge spectra at the cation and oxygen edges, is very similar to that of bulk yttria; we present and discuss simulations within the real - space full multiple scattering formalism which are quite successful in reproducing the experimental line shape. In the near - interface layer we detect the presence of silicon oxide, as reported for this and other systems previously; a new finding is that yttrium -silicon bonds are present in the interface layer, forming the precursors to the formation of yttrium silicide which develops into a long range ordered phase at higher deposition temperatures. We compare our observations with available theoretical predictions on the thermodynamic stability of yttria in comparison to silicon dioxide, yttrium silicide, and yttrium silicate; the predictions are not confirmed by experiment as far as the 2 nm thick interface layer is concerned.

We report the results of first-principles density functional theory calculations of the properties of pristine and Se doped hydrogen passivated silicon nanowires oriented along the [001] direction. We show that the effect of confinement in the orthogonal directions is to increase the bandgap as the diameter of the nanowire is progressively reduced, as expected from the simple quantum confinement model. Moreover, we observe that the introduction of surface reconstruction before H passivation can lead to an indirect bandgap due to a shift of the valence band maximum away from the convergence point. We also study the formation energy and hyperfine parameters of Se located in different positions in a nanowire with diameter of 0.8 nm. Our results confirms a tendency to surface segregation for Se atoms, probably driven by deformations close to the nanowire surface. These deformations cause also a steep decrease in the hyperfine contact term of Se in surface positions compared to the situation when Se is placed near the axis of the nanowire. The latter values of the hyperfine contact term are instead much greater than the corresponding bulk values.

As post-Si era for digital device is incipient, In0.53Ga0.47As is a good candidate among n-type active channels with high electron mobility but - unlike Si - it lacks a well-established technology for dielectric gating which may bear aggressive device scaling. Here we propose a viable route for the atomic layer deposition (ALD) of high-? dielectrics taking advantage from the well-known selfcleaning effect of the trimethylaluminum (TMA) precursor on the III-V compound surfaces. In this respect, the incorporation of Al2O3 cycles both as a pre-conditioning surface treatment and inside the ALD growth of a MO2 host matrix (M=Zr, Hf) is here investigated. Al:MO2/In0.53Ga0.47As heterojunctions have been scrutinized by in situ spectroscopic ellipsometry and ex situ chemical depth-profiling analysis which validate a good physical quality of the oxide and elucidate the effect of the pre-conditioning cycles at the interface level. The resulting MOS capacitors have been characterized by means of multifrequency capacitancevoltage measurements and conductance analysis therein yielding a permittivity of 19±1 both for Al:HfO2 and Al:ZrO2 and similar electrical quality of the interfaces. On the other hand, Al:HfO2 appears to be electrically more robust against leakage and endowed with a lower frequency dispersion in accumulation.

OBJECTIVES: To evaluate FCGR3B copy number variation (CNV) in African and European populations and to determine if FCGR3B copy number is associated with SLE and SLE nephritis risk in Afro-Caribbeans, adjusting for African genetic ancestry. METHODS: We estimated FCGR3B to determine if there were ethnic variations in CNV (unrelated unadmixed Europeans and Africans). We then examined CNV at FCGR3B in relation to SLE and SLE nephritis within a case-control collection of 134 cases of SLE (37 with SLE nephritis) and 589 population controls of mainly Afro-Caribbean descent resident in Trinidad. RESULTS: We found a significant difference in copy number FCGR3B distribution between unadmixed African and European UK cohorts, with 27 (29%) vs 3 (5%) for those with low (0 or 1) copy FCGR3B, respectively, P = 0.002. In a Trinidadian SLE case-control study, low FCGR3B CNV was associated with SLE risk 1.7 (95% CI 1.1, 2.8), P = 0.02, which remained after adjustment for African genetic ancestry; odds ratios (ORs) 1.7 (95% CI 1.0, 2.8), P = 0.04. CONCLUSION: Our studies suggest that FCGR3B low copy number is associated with SLE risk in Afro-Caribbean populations independently of CNV due to African ancestry.

Donors in silicon represent good candidates for the realization of several innovative devices exploiting classical as well as quantum information processing functionalities. Although most of the current work in the field is focused on the technological donors (P, As), the more exotic Bi offers interesting properties due to its nuclear spin and electronic structure.We present a detailed pulsed electron paramagnetic resonance study of the spin-spin and spin-lattice relaxation rates along with a full angular analysis of electron spin echo envelope modulation (ESEEM) spectra in bismuth-doped silicon samples having two different donor concentrations. The measurements were performed up to 40 K. ESEEM spectra provide information on the donor wave function via the leading superhyperfine interactions between donor nuclei and nearby 29Si coordination shells. The assignment of the most intense contributions was made on the basis of the angular variation of ESEEM resonances and elementary considerations on the deep donor states.

Emission Mossbauer spectroscopy on 57Fe fed by 57Mn ions implanted in the metal oxides ZnO, MgO and Al2O3 has been performed. The implanted ions occupy different lattice sites and charge states. A magnetic part of the spectra in each oxide can be assigned to Fe3 + ions in a paramagnetic state with unusually long relaxation time observable to temperatures up to several hundreds Kelvin. Earlier expectations that the magnetic spectra could correspond to an ordered magnetic state could not be confirmed. A clear decision for paramagnetism and against an ordered magnetic state was achieved by applying a strong magnetic field of 0.6 Tesla. The relaxation times deduced were compared to spin–lattice relaxation times from electron paramagnetic resonance (EPR).

Resistive switching characteristics of polycrystalline nickel oxide were studied for non volatile memory applications. NiO was deposited by atomic layer deposition and electron beam evaporation on silicon and various metal bottom electrodes. After an initial electroforming step, NiO based devices with Pt top electrode and Si, Pt, Ni, TiN or W bottom electrodes exihibit reproducible unipolar switching. The film physical properties as well as electrode combinations influence the programming voltages and resistance window. While Pt and Si electrodes give a reduced dispersion of programming voltages and currents, the largest resistance window (up to four order of magnitude) is obtained when W is used. Preliminary data on the switching properties of amorphous Nb2O5 and polycrystalline ZrO2 films are also discussed.

The molecular structure of tris[bis(trimethylsilyl)amido]-lutetium, [(Me3Si)(2)N](3)Lu, is investigated. An agostic interaction is found between Lu and the Si atom of the silyl group. The performance of [(Me3Si)(2)N](3)Lu as precursor to deposit Lu silicate layers by atomic layer deposition using either H2O or O-3 as oxygen source is studied. Si incorporation in the films is revealed: [(Me3Si)(2)N](3)Lu thermal decomposition and the mentioned agostic interaction contribute both to the phenomenon. [(Me3Si)(2)N](3)Lu thermal de-composition also affects the growth rate of films deposited using H2O. The growth rate of films deposited Using O-3, especially at growth temperatures < 300 degrees C, is extremely high, probably because of the hydrogen atoms existing in [(Me3Si)(2)N](3)Lu.

Scanning capacitance force microscopy and Kelvin probe force microscopy are used to image Sn nanometer sized structures embedded in silicon oxide thin films. The capacitance variation occurring between probe and sample in presence of a metallic cluster modifies the oscillation amplitude of the AFM probe at twice the frequency of the applied voltage. The extreme localisation of the interaction due to the small geometries involved allows a lateral resolution of few nm. Issues related to the contrast mechanism and the spatial resolution are discussed with the support 2D finite element calculation of the electrostatic field distribution between probe and sample.

The aim of this study was estimate the prevalence of hypertension and to identify the underlying genetic factors in the general population of an isolated village of Sardinia: Talana (~1000 inhabitants). Several lines of evidence indicate that this village has clinical similarity to the European population, while it has more power for genetic analysis than outbred population. Voluntary participants (80%) of the entire population underwent blood tests and a standardized interview collecting demographic information, living habits, clinical and family history. Hypertension was defined as SBP>= 140 and DBP>= 90 mmHg or current treatment for hypertension. SBP and DBP were normally distributed with average of 135±20 and 80±10 mmHg respectively and 26%; of the adult population of Talana was affected by hypertension. The epidemiological survey highlighted the association of the same clinical and environmental factors which were found in different populations. Eight multigenerational pedigrees, that consisted of 332 total individuals of whom 67 were affected, were constructed. The majority of the extant Talana population was genotyped using 1054 markers, which comprehend 50% of the hypertension family members. We reconstructed a genetic map using the frequencies estimated on the entire population. GWS was performed by a non-parametric analysis using SIMWALK2. We confirmed the previously described locus on chr 2 (-log10(P):3.872) and identified 8 additional loci with suggestive significance on chr 3, 4, 10, 14, 18, 19, 20 and 22. Increasing the number of markers we confirmed the loci on chromosome 18 (-log10(P): 2,97), 20 (-log10(P):2,41) and 22 (-log10(P):4). We replicated some of results in a nearby isolated village with different founders and low genetic exchange with Talana, confirming loci on chr 18 and 20, which were previously described in different populations. We are currently investigating these loci with high density SNPs map taking advantage of the extended linkage disequilibrium in our population.

Obiettivi Nell'ambito di un progetto multidisciplinare che prevede lo studio genealogico, genetico e clinico di alcune popolazioni isolate dell'Ogliastra è stata condotta un'indagine epidemiologica indirizzata a definire la prevalenza dell'ipertensione in due paesi: Talana e Perdasdefogu che si trovano in questa particolare area della Sardegna. Metodi L'arruolamento nello studio è su base volontaria. Al momento 900 soggetti, che rappresentano rispettivamente il 36% e il 20% della popolazione di Talana e Perdadefogu, hanno aderito al progetto firmando un consenso informato. Lo studio prevede la valutazione dei principali parametri ematochimici, la somministrazione di un questionario, a cura di medici specialisti, che rileva dati socio-anagrafici, abitudini di vita, esposizione ai più comuni fattori di rischio, anamnesi personale, farmacologica e familiare e la misurazione dei tratti antropometrici e della pressione arteriosa sistolica e diastolica (PAS e PAD) secondo il protocollo suggerito dall'Organizzazione Mondiale della Sanità. Risultati I soggetti visitati sono di età compresa fra i 18 e i 95 anni (età media 52±17) e le caratteristiche della maggior parte dei dati rilevati non differiscono significativamente nei due paesi: presentiamo pertanto i risultati relativi all'analisi del campione complessivo. L'andamento dei valori pressori per età e sesso non si discosta dai valori medi riscontrati in altre popolazioni e le prevalenze di ipertensione secondo la classificazione suggerita dalle linee guida della Società Europea dell'Ipertensione risultano rispettivamente del 25.3% per gli ipertesi lievi (140-159/90-99), del 7.8% per gli ipertesi moderati (160-179/100-109) e del 2.4% per gli ipertesi gravi (>180/>110). Circa il 20% del campione assume farmaci antiipertensivi ma solo il 32% di essi sembra rispondere alla terapia mentre il 43% si concentra nella classe di ipertensione lieve. Dall'analisi statistica effettuata con modelli di regressione e ANOVA la PAS cresce con l'età (p

Within Ogliastra Project, a large survey conducted in an isolated Sardinian population, we present results of an epidemiological study and of a GWS on blood pressure in Talana village (1200 inhabitants). This population may provide significant power to the identification of QTLs due to slow demographic growth, high endogamy and inbreeding, reduced genetic heterogeneity, low number of founders, stable culture and accurate genealogical records. Genotyping was carried out on 875 volunteers by a total of 654 informative markers (average het 0.71,SD=0.09) distributed over the genome (NHLBI Mammalian Genotyping Service). So far 355 individuals have undergone an extensive evaluation comprehensive of physical examination, serological analyses, anthropometrical and blood pressure measurements according to the British Hypertension Society protocol, structured interviews to collect living habits, exposure to most common risk factors, medical and medication history, information about familial disorders. Mean age is 53±19 years (55% females), SBP and DBP are normally distributed (p1.7 on chromosomes 2, 4, 6, 10 and 19 for DBP. No significant LOD score for SBP was obtained. Supported by grants from Telethon, Italy No.E1185