LISACode : A scientific simulator of LISA

A new LISA simulator (LISACode) is presented. Its ambition is to achieve a new degree of sophistication allowing to map, as closely as possible, the impact of the different sub-systems on the measurements. LISACode is not a detailed simulator at the engineering level but rather a tool whose purpose is to bridge the gap between the basic principles of LISA and a future, sophisticated end-to-end simulator. This is achieved by introducing, in a realistic manner, most of the ingredients that will influence LISA's sensitivity as well as the application of TDI combinations. Many user-defined parameters allow the code to study different configurations of LISA thus helping to finalize the definition of the detector. Another important use of LISACode is in generating time series for data analysis developments

The eLISA/NGO Data Processing Centre

International audienceData analysis for the eLISA/NGO mission is going to be performed in several steps. The telemetry is unpacked and checked at ESA's Science Operations Centre (SOC). The instrument teams are providing the necessary calibration files for the SOC to process the Level 1 data. The next steps, the source identification, parameter extraction and construction of a catalogue of sources is performed at the Data Processing Centre (DPC). This includes determining the physical and astrophysical parameters of the sources and their strain time series. At the end of the processing, the produced Level 2 and Level 3 data are then transferred back to the SOC, which provides the data archive and the interface for the scientific community. The DPC is organised by the member states of the consortium. In this paper we describe a possible outline of the data processing centre, including the tasks to be performed, and the organisational structure

How signature strengths develop positive interdependence and empowerment in an inclusive education context

This study evaluates the Individual Strengths, Collective Power! program in fostering students' use of strengths vocabulary and improving classroom relationships in an inclusive education setting in Switzerland, where students with and without special educational needs and disabilities (SEND) attend school together. The study involved 179 students, ages 8 to 12, divided into an experimental group that received specific training and an active control group that had access to program resources, regardless of their SEND status. The study used the Strengths Use Scale (SUS) and the Gratitude Questionnaire to measure students' awareness of their strengths and gratitude. In addition, a sociometric measure, the Peer Acceptance Index (PAI), was developed to assess classroom dynamics. Results indicate that strengths-based interventions significantly expanded students' vocabulary of strengths and increased positive discourse, particularly among girls. Time and age were the main predictors of positive peer commentary, rather than the interventions themselves, which had no significant effect on PAI scores. The study suggests that strengths-based tools, even without guided use, can positively influence students' language about strengths, although they did not change classroom relationships within the 9-week period. Further research is recommended to explore the specific effects and mechanisms of strengths-based interventions in inclusive settings

Signal transducer and activator of transcription 2 deficiency is a novel disorder of mitochondrial fission

Defects of mitochondrial dynamics are emerging causes of neurological disease. In two children presenting with severe neurological deterioration following viral infection we identified a novel homozygous STAT2 mutation, c.1836C4A (p.Cys612Ter), using whole exome sequencing. In muscle and fibroblasts from these patients, and a third unrelated STAT2-deficient patient, we observed extremely elongated mitochondria. Western blot analysis revealed absence of the STAT2 protein and that the mitochondrial fission protein DRP1 (encoded by DNM1L) is inactive, as shown by its phosphorylation state. All three patients harboured 15 decreased levels of DRP1 phosphorylated at serine residue 616 (P-DRP1S616), a post-translational modification known to activate DRP1, and increased levels of DRP1 phosphorylated at serine 637 (P-DRP1S637), associated with the inactive state of the DRP1 GTPase. Knockdown of STAT2 in SHSY5Y cells recapitulated the fission defect, with elongated mitochondria and decreased PDRP1 S616 levels. Furthermore the mitochondrial fission defect in patient fibroblasts was rescued following lentiviral transduction with wild-type STAT2 in all three patients, with normalization of mitochondrial length and increased P-DRP1S616 levels. Taken 20 together, these findings implicate STAT2 as a novel regulator of DRP1 phosphorylation at serine 616, and thus of mitochondrial fission, and suggest that there are interactions between immunity and mitochondria. This is the first study to link the innate immune system to mitochondrial dynamics and morphology. We hypothesize that variability in JAK-STAT signalling may contribute to the phenotypic heterogeneity of mitochondrial disease, and may explain why some patients with underlying mitochondrial disease decompensate after seemingly trivial viral infections. Modulating JAK-STAT activity may represent a novel 25 therapeutic avenue for mitochondrial diseases, which remain largely untreatable. This may also be relevant for more common neurodegenerative diseases, including Alzheimer’s, Huntington’s and Parkinson’s diseases, in which abnormalities of mitochondrial morphology have been implicated in disease pathogenesis

Strong polarization of the residual nucleus in a heavy-ion induced transfer reaction

A strong polarization of 20Ne levels has been observed in the 16O(16O, 12C)20Ne* reaction along an axis perpendicular to the reaction plane. This polarization differs from that reported in the (7Li, t) reaction, when the same nuclear levels were populated. D.W.B.A. calculations which fitted both angular distributions and polarization in the (7Li, t) reaction and which can also describe the (16O, 12C) angular distributions fail to reproduce the associated 20Ne* polarization

Space and Time pattern of mid-velocity IMF emission in peripheral heavy-ion collisions at Fermi energies

The emission pattern in the V_perp - V_par plane of Intermediate Mass Fragments with Z=3-7 (IMF) has been studied in the collision 116Sn + 93Nb at 29.5 AMeV as a function of the Total Kinetic Energy Loss of the reaction. This pattern shows that for peripheral reactions most of IMF's are emitted at mid-velocity. Coulomb trajectory calculations demonstrate that these IMF's are produced in the early stages of the reaction and shed light on geometrical details of these emissions, suggesting that the IMF's originate both from the neck and the surface of the interacting nuclei.Comment: 4 pages, 3 figures, RevTex 3.1, submitted to Phys. Rev. Letter

A Method to Address Differential Bias in Genotyping in Large-Scale Association Studies

In a previous paper we have shown that, when DNA samples for cases and controls are prepared in different laboratories prior to high-throughput genotyping, scoring inaccuracies can lead to differential misclassification and, consequently, to increased false-positive rates. Different DNA sourcing is often unavoidable in large-scale disease association studies of multiple case and control sets. Here, we describe methodological improvements to minimise such biases. These fall into two categories: improvements to the basic clustering methods for identifying genotypes from fluorescence intensities, and use of “fuzzy” calls in association tests in order to make appropriate allowance for call uncertainty. We find that the main improvement is a modification of the calling algorithm that links the clustering of cases and controls while allowing for different DNA sourcing. We also find that, in the presence of different DNA sourcing, biases associated with missing data can increase the false-positive rate. Therefore, we propose the use of “fuzzy” calls to deal with uncertain genotypes that would otherwise be labeled as missing

Amplicon-based next-generation sequencing of plasma cell-free DNA for detection of driver and resistance mutations in advanced non-small cell lung cancer

BACKGROUND: Genomic analysis of plasma cell-free DNA is transforming lung cancer care; however, available assays are limited by cost, turnaround time, and imperfect accuracy. Here, we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1, and other rare genotypes) were collected while on therapy and analyzed blinded to tumor genotype. Plasma NGS was carried out using enhanced tagged amplicon sequencing of hotspots and coding regions from 36 genes, as well as intronic coverage for detection of ALK/ROS1 fusions. Diagnostic accuracy was compared with plasma droplet digital PCR (ddPCR) and tumor genotype. RESULTS: A total of 168 specimens from 46 patients were studied. Matched plasma NGS and ddPCR across 120 variants from 80 samples revealed high concordance of allelic fraction (R2 = 0.95). Pretreatment, sensitivity of plasma NGS for the detection of EGFR driver mutations was 100% (30/30), compared with 87% for ddPCR (26/30). A full spectrum of rare driver oncogenic mutations could be detected including sensitive detection of ALK/ROS1 fusions (8/9 detected, 89%). Studying 25 patients positive for EGFR T790M that developed resistance to osimertinib, 15 resistance mechanisms could be detected including tertiary EGFR mutations (C797S, Q791P) and mutations or amplifications of non-EGFR genes, some of which could be detected pretreatment or months before progression. CONCLUSIONS: This blinded analysis demonstrates the ability of amplicon-based plasma NGS to detect a full range of targetable genotypes in NSCLC, including fusion genes, with high accuracy. The ability of plasma NGS to detect a range of preexisting and acquired resistance mechanisms highlights its potential value as an alternative to single mutation digital PCR-based plasma assays for personalizing treatment of TKI resistance in lung cancer

EUSO science

EUSO is a mission to explore the extreme universe by the probe of Ultra High Energy Cosmic Rays (UHECRs) and UHE neutrinos. EUSO monitors a gigantic volume of atmosphere from Space and measures showers induced by UHECRs and UHE neutrinos. Scientifically, it is important to measure the energy spectrum of UHECRs well beyond GZK energy with high statistics. EUSO ensures the observation of UHECRs up to 10$^{21}$eV even in the case of GZK mechanism working, and gives us a clear picture of the existence / non-existence of the GZK effect and the behavior of the spectrum beyond GZK energy, which represents the contributions from nearby sources. The anisotropy study of UHECR arrival directions in a small scale angle above GZK energy may allow us to identify individual source, because of the limited propagation distance and the high rigidity of particles. If event clusters observed by AGASA are real, it is expected from Monte Carlo simulation that EUSO will see ~100 particles from individual brightest sources and will give us a good opportunity to test the relativity in high precision. The UHE neutrino is a unique channel to explore the universe much deeper than UHECRs. EUSO essentially can measure UHE neutrinos free from background proton showers. The number of GZK neutrino events in a EUSO three years' mission is expected to be only a few. Nevertheless, it is a definitely conceivable opportunity to begin UHE neutrino astrophysics at GZK energy

Fragment Isospin as a Probe of Heavy-Ion Collisions

Isotope ratios of fragments produced at mid-rapidity in peripheral and central collisions of 114Cd ions with 92Mo and 98Mo target nuclei at E/A = 50 MeV are compared. Neutron-rich isotopes are preferentially produced in central collisions as compared to peripheral collisions. The influence of the size (A), density, N/Z, E*/A, and Eflow/A of the emitting source on the measured isotope ratios was explored by comparison with a statistical model (SMM). The mid-rapidity region associated with peripheral collisions does not appear to be neutron-enriched relative to central collisions.Comment: 12 pages including figure