Four-Formation In-Track Configuration Maintenance Strategy

The aim of this paper is to present the analysis conducted by CNES for the maintenance of a formation made of several LEO satellites (typically 4) in several planes (typically 2), 100 km or so apart from each other. The along-track separations between the satellites have to be controlled to within 15 km thanks to orbit correction maneuvers supposed to be performed every 2 weeks. The main difficulty is related to solar activity which is expected to be close to its maximum for the entire mission s lifespan. As a matter of fact, a high solar activity makes orbit prediction harder, and makes it impossible to keep the altitude of the formation constant. Thus, a specific relative maintenance strategy had to be devised in order to meet the mission's requirements. The first part provides a few elements on the mission analysis process that has taken place. The method used for the evaluation of the maneuver frequency is detailed, based on the evaluation of the effects of atmospheric drag on the orbit. The second part is dedicated to the maintenance strategy that has been designed, and particularly to the computation of the reference orbits and of the velocity increments that enable the in-track inter-satellite distances to be maintained within the desired bounds. Finally a few simulation results are presented; they enable the performance of the maintenance strategy to be checked in a more realistic context

LETEC (Learning and Teaching Corpus) Simuligne

Learning and Teaching Corpus of the online educational experiment Simuligne (2001). Its scenario is based on a global simulation for the learning of French as a foreign language. It also includes an intercultural activity, "Interculture", based on the Cultura project. The corpus includes the pedagogical scenario, described in several formats, the research protocol, participant's online interactions and productions (structured in XML), list of participants, licences of use.\ud The LETEC corpus associated (mce.simu.all.all-CP.zip) is organized as an IMS-CP archive. We define a Learning & Teaching Corpus as a structured entity containing all the elements resulting from a communicative on-line learning situation, whose context is described by an educational scenario and a research protocol. The core data collection includes all the interaction data, the productions of the course participants, and the tracks, resulting from the participants’ actions in the learning environment and stored according to the research protocol. In order to be able to be shared, and to respect participant privacy, these data should be anonymised and a license for its use be provided in the corpus. A derived analysis can be linked to a given set of data under consideration, used or computerized for this analysis. An analysis consisting in data annotation/transcription/transformation, accurately connected to its original data, can be merged with the corpus itself, in order for other researchers to compare their own results on a concurrent analysis or to build their complementary analysis upon these results.\ud The definition of a Learning & Teaching Corpus as a whole entity comes from the need of explicit links, between interaction data, context and analyses. This explicit context is crucial for an external researcher to interpret the data and to perform its own analyses.\ud This definition seeks to capture the context of the data stemming from the course in order to allow a researcher to look for, understand and connect this information whether or not he/she was involved in the original course. More details about a LETEC corpus an ist structure at : http://mulce.univ-fcomte.fr/metadata/LETECorpus-en.pd

STAT3 mutation impacts biological and clinical features of T-LGL leukemia

STAT3 mutations have been described in 30-40% of T-large granular lymphocyte (T-LGL) leukemia patients, leading to STAT3 pathway activation. Considering the heterogeneity of the disease and the several immunophenotypes that LGL clone may express, the aim of this work was to evaluate whether STAT3 mutations might be associated with a distinctive LGL immunophenotype and/or might be indicative for specific clinical features.Our series of cases included a pilot cohort of 101 T-LGL leukemia patients (68 CD8+/CD4- and 33 CD4+/CD8\ub1) from Padua Hematology Unit (Italy) and a validation cohort of additional 20 patients from Rennes Hematology Unit (France).Our results indicate that i) CD8+ T-LGL leukemia patients with CD16+/CD56- immunophenotype identify a subset of patients characterized by the presence of STAT3 mutations and neutropenia, ii) CD4+/CD8\ub1 T-LGL leukemia are devoid of STAT3 mutations but characterized by STAT5b mutations, and iii) a correlation exists between STAT3 activation and presence of Fas ligand, this molecule resulting highly expressed in CD8+/CD16+/CD56- patients. Experiments with stimulation and inhibition of STAT3 phosphorylation confirmed this relationship. In conclusion, our data show that T-LGL leukemia with specific molecular and phenotypic patterns is associated with discrete clinical features contributing to get insights into molecular bases accounting for the development of Fas ligand-mediated neutropenia

A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (γ-glutamyl transpeptidase, alanine aminotransferase, α(2)-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When γ-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of γ-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of γ-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and γ-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed

ELISA based assays to measure adenosine deaminases concentration in serum and saliva for the diagnosis of ADA2 deficiency and cancer

Adenosine deaminases (ADAs) are enzymes of purine metabolism converting adenosine to inosine. There are two types of ADAs in humans ADA1 and ADA2. While both ADA1 and ADA2 share the same substrate, they differ in expression, cellular localization, and catalytic properties. The genetic deficiency of ADA1 results in severe combined immunodeficiency (SCID), while lack in ADA2 (DADA2) results in multiple phenotypes ranging from systemic inflammation to vascular pathology. Clinical studies have shown that the levels of ADAs in biological fluids are altered in pathophysiological conditions, suggesting that ADA activity could be a convenient marker for the diagnosis of immune diseases and cancer. Here, we describe sensitive and straightforward ELISA assays to measure ADA1 and ADA2 concentrations in biological fluids. Analysis of the serum and saliva samples from the healthy controls and DADA2 patients revealed that ADA2 enzyme concentration is significantly lower in patients than in healthy controls. In contrast, the concentration of ADA2 increases in the serum of patients with large granular leukocyte leukemia (LGLL) and patients' saliva with head and neck cancer. Thus, this simple, non-invasive method allows for distinguishing healthy controls from the affected patient. It can be implemented in screening and diagnosis of DADA2 and follow up the treatment of LGLL and several types of head and neck cancer

ELISA based assays to measure adenosine deaminases concentration in serum and saliva for the diagnosis of ADA2 deficiency and cancer

Adenosine deaminases (ADAs) are enzymes of purine metabolism converting adenosine to inosine. There are two types of ADAs in humans ADA1 and ADA2. While both ADA1 and ADA2 share the same substrate, they differ in expression, cellular localization, and catalytic properties. The genetic deficiency of ADA1 results in severe combined immunodeficiency (SCID), while lack in ADA2 (DADA2) results in multiple phenotypes ranging from systemic inflammation to vascular pathology. Clinical studies have shown that the levels of ADAs in biological fluids are altered in pathophysiological conditions, suggesting that ADA activity could be a convenient marker for the diagnosis of immune diseases and cancer. Here, we describe sensitive and straightforward ELISA assays to measure ADA1 and ADA2 concentrations in biological fluids. Analysis of the serum and saliva samples from the healthy controls and DADA2 patients revealed that ADA2 enzyme concentration is significantly lower in patients than in healthy controls. In contrast, the concentration of ADA2 increases in the serum of patients with large granular leukocyte leukemia (LGLL) and patients’ saliva with head and neck cancer. Thus, this simple, non-invasive method allows for distinguishing healthy controls from the affected patient. It can be implemented in screening and diagnosis of DADA2 and follow up the treatment of LGLL and several types of head and neck cancer

Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration

KRAS Mutation Detection in Paired Frozen and Formalin-Fixed Paraffin-Embedded (FFPE) Colorectal Cancer Tissues

KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients. However, most studies of KRAS mutation analysis have been performed using homogenously archived CRC specimens, and studies that compare freshly frozen specimens and formalin-fixed paraffin-embedded (FFPE) specimens of CRC are lacking. The aim of the present study was to evaluate the impact of tissue preservation on the determination of KRAS mutational status. A series of 131 mCRC fresh-frozen tissues were first analyzed using both high-resolution melting (HRM) and direct sequencing. KRAS mutations were found in 47/131 (35.8%) using both approaches. Out of the 47 samples that were positive for KRAS mutations, 33 had available matched FFPE specimens. Using HRM, 2/33 (6%) demonstrated suboptimal template amplification, and 2/33 (6%) expressed an erroneous wild-type KRAS profile. Using direct sequencing, 6/33 (18.1%) displayed a wild-type KRAS status, and 3/33 (9.1%) showed discordant mutations. Finally, the detection of KRAS mutations was lower among the FFPE samples compared with the freshly frozen samples, demonstrating that tissue processing clearly impacts the accuracy of KRAS genotyping

Asteroid (16) Psyche’s primordial shape: A possible Jacobi ellipsoid

Context. Asteroid (16) Psyche is the largest M-type asteroid in the main belt and the target of the NASA Psyche mission. It is also the only asteroid of this size (D >  200 km) known to be metal rich. Although various hypotheses have been proposed to explain the rather unique physical properties of this asteroid, a perfect understanding of its formation and bulk composition is still missing. Aims. We aim to refine the shape and bulk density of (16) Psyche and to perform a thorough analysis of its shape to better constrain possible formation scenarios and the structure of its interior. Methods. We obtained disk-resolved VLT/SPHERE/ZIMPOL images acquired within our ESO large program (ID 199.C-0074), which complement similar data obtained in 2018. Both data sets offer a complete coverage of Psyche’s surface. These images were used to reconstruct the three-dimensional (3D) shape of Psyche with two independent shape modeling algorithms (MPCD and ADAM). A shape analysis was subsequently performed, including a comparison with equilibrium figures and the identification of mass deficit regions. Results. Our 3D shape along with existing mass estimates imply a density of 4.20  ±  0.60 g cm−3, which is so far the highest for a solar system object following the four telluric planets. Furthermore, the shape of Psyche presents small deviations from an ellipsoid, that is, prominently three large depressions along its equator. The flatness and density of Psyche are compatible with a formation at hydrostatic equilibrium as a Jacobi ellipsoid with a shorter rotation period of ∼3h. Later impacts may have slowed down Psyche’s rotation, which is currently ∼4.2 h, while also creating the imaged depressions. Conclusions. Our results open the possibility that Psyche acquired its primordial shape either after a giant impact while its interior was already frozen or while its interior was still molten owing to the decay of the short-lived radionuclide 26Al.Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 199.C-0074 (principal investigator: P. Vernazza). P. Vernazza, A. Drouard, M. Ferrais and B. Carry were supported by CNRS/INSU/PNP. J.H. and J.D. were supported by grant 18-09470S of the Czech Science Foundation and by the Charles University Research Programme no. UNCE/SCI/023. E.J. is F.R.S.-FNRS Senior Research Associate. The work of TSR was carried out through grant APOSTD/2019/046 by Generalitat Valenciana (Spain). This work was supported by the MINECO (Spanish Ministry of Economy) through grant RTI2018-095076-B-C21 (MINECO/FEDER, UE)

Validation of TROPOMI Surface UV Radiation Product

The TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor (S5P) satellite was launched on 13 October 2017 to provide the atmospheric composition for atmosphere and climate research. The S5P is a sun-synchronous polar-orbiting satellite providing global daily coverage. The TROPOMI swath is 2600 km wide, and the ground resolution for most data products is 7.2x3.5 km2 (5.6x3.5 km2 since 6 August 2019) at nadir. The Finnish Meteorological Institute (FMI) is responsible for the development and processing of the TROPOMI Surface Ultraviolet (UV) Radiation Product which includes 36 UV parameters in total. Ground-based data from 25 sites located in arctic, subarctic, temperate, equatorial and antarctic areas were used for validation of TROPOMI overpass irradiance at 305, 310, 324 and 380 nm, overpass erythemally weighted dose rate / UV index and erythemally weighted daily dose for the period from 1 January 2018 to 31 August 2019. The validation results showed that for most sites 60–80% of TROPOMI data was within ±20% from ground-based data for snow free surface conditions. The median relative differences to ground-based measurements of TROPOMI snow free surface daily doses were within ±10% and ±5% at two thirds and at half of the sites, respectively. At several sites more than 90% of clear sky TROPOMI data were within ±20% from ground-based measurements. Generally median relative differences between TROPOMI data and ground-based measurements were a little biased towards negative values, but at high latitudes where nonhomogeneous topography and albedo/snow conditions occurred, the negative bias was exceptionally high, from -30% to -65%. Positive biases of 10–15% were also found for mountainous sites due to challenging topography. The TROPOMI Surface UV Radiation Product includes quality flags to detect increased uncertainties in the data due to heterogeneous surface albedo and rough terrain which can be used to filter the data retrieved under challenging conditions