Testing Disk-Locking in NGC 2264

We test analytic predictions from different models of magnetospheric accretion, which invoke disk-locking, using stellar and accretion parameters derived from models of low resolution optical spectra of 36 T Tauri stars (TTSs) in NGC 2264 (age~3 Myrs). Little evidence is found for models that assume purely dipolar field geometries; however, strong support is found in the data for a modified version of the X-wind model (Shu et al. 1994) which allows for non-dipolar field geometries. The trapped flux concept in the X-wind model is key to making the analytic predictions which appear supported in the data. By extension, our analysis provides support for the outflows predicted by the X-wind as these also originate in the trapped flux region. In addition, we find no support in the data for accretion powered stellar winds from young stars. By comparing the analysis presented here of NGC 2264 with a similar analysis of stars in Taurus (age~1-2 Myr), we find evidence that the equilibrium interaction between the magnetic field and accretion disk in TTS systems evolves as the stars grow older, perhaps as the result of evolution of the stellar magnetic field geometry. We compare the accretion rates we derive with accretion rates based on U-band excess, finding good agreement. In addition, we use our accretion parameters to determine the relationship between accretion and H-beta luminosity, again finding good agreement with previously published results; however, we also find that care must be used when applying this relationship due to strong chromospheric emission in young stars which can lead to erroneous results in some cases.Comment: 66 pages, 15 figures, 13 table

Very accurate cryogenic mechanisms for CRIRES+

After 5 years of operation on the VLT, a large upgrade of CRIRES (the ESO Cryogenic InfraRed Echelle Spectrograph) was decided mainly in order to increase the efficiency. Using a cross dispersion design allows better wavelength coverage per exposure. This means a complete re-design of the cryogenic pre-optic which were including a predispersion stage with a large prism as dispersive element. The new design requires a move of the entrance slit and associated decker toward the first intermediate focal plane right behind the window. Implement 2 functions with high positioning accuracy in a pre-defined and limited space was a real challenge. The design and the test results recorded in the ESO Cryogenic Test Facility are reported in this paper. The second critical function is the grating wheel which positions the 6 cross disperser gratings into the beam. The paper describes the design of the mechanism which includes a detente system in order to guaranty the 5 arc sec positioning reproducibility requested. The design includes also feedback system, based on switches, in order to ensure that the right grating is in position before starting a long exposure. The paper reports on the tests carried out at cryogenic temperature at the sub-system level. It also includes early performances recorded in the instrument along the first phases of the system test

Maryann Hondo, IBM

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Maximum extent and readvance dynamics of the Irish Sea Ice Stream since the Last Glacial Maximum

International audienceThe Irish Sea Ice Stream (ISIS) has long had one of the best documented retreat histories of the British-Irish Ice Sheet (BIIS) and was the first ice stream to be constrained by Bayesian analysis of geochronological data. These attributes made it a model system for the BRITICE-CHRONO research project, which aims to produce the best constrained retreat record of any palaeo-ice sheet contributing key observational constraints for ice sheet modelling. The project has generated a suite of new radiocarbon ages from deglacial sequences offshore in the Celtic and Irish seas and terrestrial cosmogenic nuclide and optically-stimulated luminescence ages from ice-marginal sites in the Isles of Scilly, Ireland, Wales and NW England. The ISIS was unusual within the former BIIS, in that it was a compound ice stream with two outlets, one marine terminating that flowed through the Irish Sea Basin into the Celtic Sea, and a terrestrial terminus that flowed southwards through Cheshire-Shropshire lowlands into the English Midlands around 25.5 ka. Here we assess the retreat dynamics across the entirety of the ISIS, integrating the new chronology in a revised Bayesian analysis that constrains the pattern and timing ice marginal fluctuations. The retreat chronology in the Irish Sea is better constrained than in the Celtic Sea, where the ISIS is now recognised to have extended as far as the continental shelf break to the SW of Britain and Ireland between 24 and 27 ka; this advance was synchronous with independently-dated ice-rafted detritus from ISIS in adjacent deep-sea cores. The ISIS then retreated rapidly northwards through the Celtic Sea, with evidence for readvance phases, deglaciating the Isles of Scilly at 25.5 ka, reaching St Georges Channel by 24.3 ka and the Llŷn Peninsula by 23.9 ka. The initiation of retreat from both the eastern (terrestrial) and western (marine) components of ISIS was synchronous. The eastern terrestrial lobe had vacated the Cheshire-Shropshire lowlands by 22-21 ka. The complex readvance sequences identified on the Llŷn (24-20ka) and in eastern Ireland have now been tightly constrained to register centennial-scale oscillations of the ice front driven by internal ice dynamics over topographic pinning points and constrictions of the ice-stream. Retreat northwards into the northern Irish Sea then accelerated, first evacuating the deeper water of the western Irish Sea, and developing pronounced ice margins across the northern Isle of Man by 19.1 ka. The final retreat phase, with ice margins pulling back onto terrestrial settings in the English Lake District, the north of Ireland and SW Scotland around 17 ka, was a deglaciation accomplished in a fully marine context evidenced by the preservation on the seabed of subglacial landforms and by increasing influence of local ice sources with flow realignment during draw-down and ice margin retreat

261 Association of T-cell–inflamed gene expression profile and PD-L1 status with efficacy of pembrolizumab in patients with esophageal cancer from KEYNOTE-180

BackgroundKey biomarkers under investigation for the ability to predict response to monotherapy PD-1 inhibitors such as pembrolizumab include PD-L1, TMB, MSI, and T-cell–inflamed gene expression profile (GEP). The KEYNOTE-180 trial (NCT02559687) was a single-arm phase 2 study of pembrolizumab as third-line or greater therapy in advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma (SCC). ORR was 9.9% and median DOR was NR at the primary analysis. We investigated the relationship in KEYNOTE-180 between response to pembrolizumab and T-cell–inflamed GEP or PD-L1 expression by histology.MethodsPatients received pembrolizumab 200 mg Q3W for ≤2 years until disease progression, toxicity, or withdrawal. The end points for this analysis were ORR, DOR, and PFS per RECIST v1.1 by central review and OS in the SCC and adenocarcinoma populations by GEP (non-low [≥–1.540] or low [<–1.540]; cutoff prespecified) and PD-L1 (CPS ≥10 or <10). Tumor GEP was determined using the NanoString nCounter Analysis System. PD-L1 expression was characterized using PD-L1 IHC 22C3 pharmDx. Data cutoff date was July 30, 2018.ResultsOf 121 total patients, 118 had an evaluable GEP score and 121 had an evaluable PD-L1 CPS. Fifty-one patients (42.1%) had GEPnon-lowtumors, 58 (48.0%) had CPS ≥10 tumors, and 31 (25.6%) had GEPnon-low/CPS ≥10 tumors; 63 patients (52.1%) had SCC and 58 (47.9%) had adenocarcinoma. ORR was 15.4% with GEPnon-low and 13.5% with GEPlow among patients with SCC and 12% and 0% among patients with adenocarcinoma, respectively (table 1). ORR was 20% with CPS ≥10 and 7.1% with CPS <10 among patients with SCC and 4.3% and 5.7%, respectively, among patients with adenocarcinoma (table 2). Median OS was slightly higher among patients with SCC in the GEPnon-low subgroup and the CPS ≥10 subgroup versus GEPlow and CPS <10 subgroups, respectively (tables 1, 2); this trend was reversed among patients with adenocarcinoma (tables 1, 2). Median PFS ranged from 1.9 to 2.1 across histology/biomarker subgroups. Median DOR was NR regardless of GEP or CPS status (tables 1, 2).Abstract 261 Table 1Response by GEP status and histologyaAnalysis by biomarker status was not possible because of the small sample size.Abstract 261 Table 2Response by PD-L1 status and histologyaAnalysis by biomarker status was not possible because of the small sample size.ConclusionsIn KEYNOTE-180, data in a small number of patients suggested that measures of inflammation, like PD-L1 and GEP, may enrich for responses to pembrolizumab. In SCC, some trends toward enrichment were observed for both biomarkers, although the trend was stronger for PD-L1 CPS ≥10. In adenocarcinoma, a trend was observed for GEP but not for PD-L1; the small number of responders is limiting, and further studies are needed to understand molecular correlates in adenocarcinoma.AcknowledgementsMedical writing and/or editorial assistance was provided by Tim Peoples, MA, ELS, and Holly C. Cappelli, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicalTrials. gov, NCT02559687Ethics ApprovalThe study and the protocol were approved by the institutional review board or ethics committee at each site.ConsentAll patients provided written informed consent to participate in the clinical trial