High rate, fast timing Glass RPC for the high η\eta CMS muon detectors

The HL-LHC phase is designed to increase by an order of magnitude the amount of data to be collected by the LHC experiments. To achieve this goal in a reasonable time scale the instantaneous luminosity would also increase by an order of magnitude up to $6 \cdot 10^{34}$ cm$^{-2}$s$^{-1}$. The region of the forward muon spectrometer ($|\eta| > 1.6$) is not equipped with RPC stations. The increase of the expected particles rate up to 2 kHz/cm$^2$ ( including a safety factor 3 ) motivates the installation of RPC chambers to guarantee redundancy with the CSC chambers already present. The actual RPC technology of CMS cannot sustain the expected background level. A new generation Glass-RPC (GRPC) using low resistivity glass (LR) is proposed to equip at least the two most far away of the four high eta muon stations of CMS. The design of small size prototypes and the studies of their performances under high rate particles flux is presented.Comment: 5 pages, 5 figures, proceeding for the conference VCI 201

8q24 Cancer Risk Allele Associated with Major Metastatic Risk in Inflammatory Breast Cancer

BACKGROUND: Association studies have identified low penetrance alleles that participate to the risk of cancer development. The 8q24 chromosomal region contains several such loci involved in various cancers that have been recently studied for their propensity to influence the clinical outcome of prostate cancer. We investigated here two 8q24 breast and colon cancer risk alleles in the close vicinity of the MYC gene for their role in the occurrence of distant metastases. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective series of 449 patients affected with breast or colon adenocarcinoma was genotyped for the rs13281615 and/or rs6983267 SNPs. Statistical analyses were done using the survival package v2.30 in the R software v2.9.1. The two SNPs did not influence the development of distant metastases of colon cancer; rs6983267 showed a mild effect on breast cancer. However, this effect was greatly emphasized when considering inflammatory breast cancer (IBC) solely. Replicated on a larger and independent series of IBC the contribution of the genotype to the metastatic risk of IBC was found an independent predictor of outcome (p = 2e-4; OR 8.3, CI95:2.6-33). CONCLUSIONS/SIGNIFICANCE: Our study shows first that the monitoring of this specific germline variation may add a substantial tool for IBC prognostication, an aggressive disease that evolves towards distant metastases much more frequently than non-IBC and for which no reliable prognostic factor is available in medical practice. Second, it more generally suggests that risk alleles, while associated with low susceptibility, could correlate with a high risk of metastasis

X-ray Absorption Near-Edge Structure calculations with pseudopotentials. Application to K-edge in diamond and alpha-quartz

We present a reciprocal-space pseudopotential scheme for calculating X-ray absorption near-edge structure (XANES) spectra. The scheme incorporates a recursive method to compute absorption cross section as a continued fraction. The continued fraction formulation of absorption is advantageous in that it permits the treatment of core-hole interaction through large supercells (hundreds of atoms). The method is compared with recently developed Bethe-Salpeter approach. The method is applied to the carbon K-edge in diamond and to the silicon and oxygen K-edges in alpha-quartz for which polarized XANES spectra were measured. Core-hole effects are investigated by varying the size of the supercell, thus leading to information similar to that obtained from cluster size analysis usually performed within multiple scattering calculations.Comment: 11 pages, 4 figure

Coeval extensional shearing and lateral underflow during Late Cretaceous core complex development in the Niğde Massif, Central Anatolia, Turkey

27 p.International audienceThe Nig¢de Massif, at the southern tip of the Central Anatolian Crystalline Complex, consists of two structural units. Foliations in the lower unit define a dome cored by migmatites. The contact between the two units bears all the elements of a ductile to brittle extensional detachment. Hence the Nig¢de Massif represents an extensional metamorphic core complex. Top-to-NE/ENE shearing at higher levels of the lower unit relates to displacement along the detachment. Deeper levels of the lower unit display hightemperature top-to-SSW ductile shearing. The two shearing deformations show a difference in the mean trend of stretching lineations of up to 58. New 40Ar/39Ar ages combined with previously published data enable us to infer that the two shears were contemporaneous. In our favored interpretation, oblique shearing in the core of the dome reflects lateral underflow, i.e., horizontal flowing of the lower crust in a direction highly oblique to the direction of extension. As a result of the interaction between lateral underflow and downdip shearing along the overlying detachment, distinct structural domains are expected to exist within the migmatitic part of the core complex, with observed counterparts in the Nig¢de dome. Lateral underflow may reflect ''inward'' flow on the scale of the core complex. Regional-scale channel flow is an alternative that would better account for the record of non-coaxial deformation in the core of the dome. More generally, we suspect that the development of lateral underflow in a metamorphic core complex more likely reflects regional channel flow, rather than local inward flow

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

International audienceBackground: Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity.Methods: We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced.Results: Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients.Conclusion: This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit

Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder due to a defect in the nucleotide excision repair (NER) DNA repair pathway, characterized by severe sunburn development of freckles, premature skin aging, and susceptibility to develop cancers at an average age of eight. XP is an example of accelerated photo-aging. It is a genetically and clinically heterogeneous disease. Eight complementation groups have been described worldwide. In Tunisia, five groups have been already identified. In this work, we investigated the genetic etiology in a family with an atypically mild XP phenotype. Two Tunisian siblings born from first-degree consanguineous parents underwent clinical examination in the dermatology department of the Charles Nicolle Hospital on the basis of acute sunburn reaction and mild neurological disorders. Blood samples were collected from two affected siblings after written informed consent. As all mutations reported in Tunisia have been excluded using Sanger sequencing, we carried out mutational analysis through a targeted panel of gene sequencing using the Agilent HaloPlex target enrichment system. Our clinical study shows, in both patients, the presence of achromic macula in sun exposed area with dermatological feature suggestive of Xeroderma pigmentosum disease. No developmental and neurological disorders were observed except mild intellectual disability. Genetic investigation shows that both patients were carriers of an homozygous T to C transition at the nucleotide position c.2333, causing the leucine to proline amino acid change at the position 778 (p.Leu778Pro) of the ERCC5 gene, and resulting in an XP-G phenotype. The same variation was previously reported at the heterozygous state in a patient cell line in Europe, for which no clinical data were available and was suggested to confer an XP/CS phenotype based on functional tests. This study contributes to further characterization of the mutation spectrum of XP in consanguineous Tunisian families and is potentially helpful for early diagnosis. It also indicates that the genotype-phenotype correlation is not always coherent for patients with mild clinical features. These data therefore suggest that targeted NGS is a highly informative diagnostic strategy, which can be used for XP molecular etiology determination

Écriture et transmission des savoirs de l’Antiquité à nos jours

Pendant longtemps, la transmission des savoirs s’est faite directement, du maître à l’élève, de l’artisan à l’apprenti, par un enseignement oral que venait compléter la démonstration des gestes de la pratique. L’apparition de l’écriture, et plus encore la diffusion de la literacy ont fait que des méthodes de transmission indirectes ont pu se faire jour et que l’acquisition d’un savoir, quel qu’il soit, a pu se faire sans contact immédiat avec le détenteur de ce savoir, mais par le truchement d’un livre ou d’une autre forme d’écrit. Il s’est ensuivi une capacité de diffusion des savoirs quasiment illimitée, des plus techniques et spécialisés aux plus abstraits et généralistes. C’est cette explosion de la transmission des savoirs que les vingt auteurs des contributions ici réunies ont cherché à explorer en mettant en lumière différentes facettes, à travers une série d’exemples, allant de l’Antiquité à l’époque contemporaine. Le Congrès national des sociétés historiques et scientifiques rassemble chaque année universitaires, membres de sociétés savantes et jeunes chercheurs. Ce recueil est issu de travaux présentés lors du 143e Congrès sur le thème « La transmission des savoirs »

Macrophage IL-1β-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic arthritis

ObjectiveIL-1β is a leaderless cytokine with poorly known secretory mechanisms that is barely detectable in serum of patients, including those with an IL-1β-mediated disease such as systemic juvenile idiopathic arthritis (sJIA). Leukocyte microvesicles (MVs) may be a mechanism of IL-1β secretion. The first objective of our study was to characterize IL-1β-positive MVs obtained from macrophage cell culture supernatants and to investigate their biological functions in vitro and in vivo. The second objective was to detect circulating IL-1β-positive MVs in JIA patients.MethodsMVs were purified by serial centrifugations from PBMCs, or THP-1 differentiated into macrophages, then stimulated with LPS ± ATP. MV content was analyzed for the presence of IL-1β, NLRP3 inflammasome, caspase-1, P2X7 receptor, and tissue factor (TF) using ELISA, Western blot, or flow cytometry. MV biological properties were studied in vitro by measuring VCAM-1, ICAM-1, and E-selectin expression after HUVEC co-culture and factor-Xa generation test was realized. In vivo, MVs’ ability to recruit leukocytes in a murine model of peritonitis was evaluated. Plasmatic IL-1β-positive MVs were studied ex vivo in 10 active JIA patients using flow cytometry.ResultsTHP-1-derived macrophages stimulated with LPS and ATP released MVs, which contained NLRP3, caspase-1, and the 33-kDa precursor and 17-kDa mature forms of IL-1β and bioactive TF. IL-1β-positive MVs expressed P2X7 receptor and released soluble IL-1β in response to ATP stimulation in vitro. In mice, MVs induced a leukocyte peritoneal infiltrate, which was reduced by treatment with the IL-1 receptor antagonist. Finally, IL-1β-positive MVs were detectable in plasma from 10 active JIA patients.ConclusionMVs shed from activated macrophages contain IL-1β, NLRP3 inflammasome components, and TF, and constitute thrombo-inflammatory vectors that can be detected in the plasma from active JIA patients

The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge