Additive manufacturing processes and especially the family of laser powder bed fusion technologies have a great industrial potential since it enables, from metal powder beds, to produce full density ...complex monolithic parts. The high-temperature gradient resulting from the locally concentrated energy input leads to strong temperature fields driving non-negligible residual stress gradients, part deformations and crack formation. Resulting stress and texture gradients arise from the interdependent physical phenomena (metallurgical, thermal, mechanical and fluid mechanics) occurring during the process. Present work focuses on the residual stress being built in an austenitic stainless steel cubical shaped part of 1 cm side, prepared by a laser powder bed fusion process from a gas-atomized metallic powder (from martensitic X40CrMoVN16-2 stainless steel), through a full residual stress tensor mapping achieved thanks to neutron diffraction. Stress analyses incorporate morphological and crystallographic textures, as well as elastic anisotropy. Components of the principal stress tensor display compressive values close to the baseplate that develop into low compression, and a tensile stress state at the subsurface (surrounding thermal history effects). Results also underline the strong impact of matter environment (and thus thermal environment) onto stress gradient magnitude and the complex loading origins of the residual stress.
The thermomechanical behavior of polycrystalline sheets of high purity copper with various numbers of grains (d) across the thickness (t) is experimentally analyzed. As for other face centered cubic ...materials, the t/d ratio strongly affects the work hardening of copper, especially for t/d values lower than a critical one around five. These results are in agreement with previous ones concerning nickel and can be correlated with surface effects which progressively take place in the material when few grains are present across the thickness. The t/d ratio mainly affects the second work hardening stage and an increase in temperature tends to reduce this effect due to the early beginning of cross slip which leads to a generalization of the surface properties on the overall volume of the material. This result is supported by the analysis of the dislocation structures during the second and third hardening stages for polycrystalline and multicrystalline specimens. As a consequence, the forming of thin metallic products should be ideally performed at moderate temperatures in order to avoid size effects which can deteriorate the reliability of the final product.
It is the purpose of this paper to provide a comprehensive documentation of the new NCAR (National Center for Atmospheric Research) version of the spectral element (SE) dynamical core as part of the ...Community Earth System Model (CESM2.0) release. This version differs from previous releases of the SE dynamical core in several ways. Most notably the hybrid sigma vertical coordinate is based on dry air mass, the condensates are dynamically active in the thermodynamic and momentum equations (also referred to as condensate loading), and the continuous equations of motion conserve a more comprehensive total energy that includes condensates. Not related to the vertical coordinate change, the hyperviscosity operators and the vertical remapping algorithms have been modified. The code base has been significantly reduced, sped up, and cleaned up as part of integrating SE as a dynamical core in the CAM (Community Atmosphere Model) repository rather than importing the SE dynamical core from High‐Order Methods Modeling environment as an external code.
Key Points
The CESM2.0 release of the spectral element dynamical core (CAM‐SE) is documented
Model has comprehensive treatment of condensates and energy
The CAM‐SE model has been sped up significantly compared to its predecessor CAM‐HOMME
•The influence of temperature on the size effects in some fcc polycrystals is reported.•High stacking fault energy polycrystals always behave differently than multicrystals.•Work hardening of low ...stacking fault energy polycrystals tends toward multicrystals one.•Surface effects and grain size influence can be successfully dissociated.•Formability of thin parts can be optimized by appropriate strain paths and temperature.
The mechanical behavior of face centered cubic metals is deeply affected when specimen dimensions decrease from a few millimeters to a few micrometers. At room temperature, a critical thickness (t) to grain size (d) ratio (t/d)c was previously highlighted, under which the softening of mechanical properties became very pronounced both in terms of Hall–Petch relation and work hardening mechanisms. In this work, new experimental results are provided concerning the influence of temperature on this size effect for copper, nickel and Ni–20wt.%Cr, representative of a wide range of deformation mechanisms (i.e. dislocation slip character). It is shown that multicrystalline samples (t/d<(t/d)c) are not deeply affected by an increase in temperature, independently of the planar or wavy character of dislocation glide. For pronounced wavy slip character metals, surface effects in polycrystals (t/d>(t/d)c) are not significant enough to reduce the gap between polycrystal and multicrystal mechanical behavior when the temperature increases. However, a transition from wavy slip to planar glide mechanisms induces a modification of the polycrystalline behavior which tends toward multicrystalline one with a moderate increase in temperature. This work demonstrates that surface effects and grain size influence can be successfully disassociated for the three studied materials using an analysis supported by the Kocks–Mecking formalism. All these results are supported by microscopic investigations of dislocation substructures and compared to numerical simulations using a strain gradient plasticity model.
In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified ...exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23–41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 95% confidence interval (CI): 0.57, 0.77. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival 0.63 (95% CI: 0.45, 0.89) and newly collected samples 0.53 (95% CI: 0.38, 0.72). In patients with TPS ≥1%, PFS HRs were similar across archival 0.82 (95% CI: 0.66, 1.02) and newly collected samples 0.83 (95% CI: 0.68, 1.02).
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then ...assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC).
Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance.
From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported.
Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified.
NCT02034981.
OBJECTIVE: To confirm the apparent effectiveness of botulinum toxin (BTX) in hemiparetic patients with ankle plantar flexors and foot invertor spasticity. METHODS: Twenty three hemiparetic patients ...with spasticity of the ankle plantar flexors and foot invertors were included in a randomised double blind, placebo controlled study with BTX. Patients were examined on days 0, 30, 90, and 120 and received one injection of BTX and one of placebo in a random order at day 0 and day 90. RESULTS: Patients reported a clear subjective improvement in foot spasticity after BTX (P = 0.0014) but not after placebo. Significant changes were noted in Ashworth scale values for ankle extensors (P < 0.0001) and invertors (P = 0.0002), and for active ankle dorsiflexion (P = 0.0001). Gait velocity was slightly but not significantly (P = 0.0731) improved after BTX injections. The severity of spasticity did not modify treatment efficacy, but BTX was less effective in patients with longer duration of spasticity (P = 0.0081). CONCLUSION: The efficacy of BTX injections in the treatment of spastic foot suggests that BTX may be particularly useful during the first year after a stroke.
DCMIP2016: the tropical cyclone test case Willson, Justin L; Reed, Kevin A; Jablonowski, Christiane ...
Geoscientific Model Development,
04/2024, Letnik:
17, Številka:
7
Journal Article
Recenzirano
Odprti dostop
This paper describes and analyzes the Reed–Jablonowski (RJ) tropical cyclone (TC) test case used in the 2016 Dynamical Core Model Intercomparison Project (DCMIP2016). This intermediate-complexity ...test case analyzes the evolution of a weak vortex into a TC in an idealized tropical environment. Reference solutions from nine general circulation models (GCMs) with identical simplified physics parameterization packages that participated in DCMIP2016 are analyzed in this study at 50 km horizontal grid spacing, with five of these models also providing solutions at 25 km grid spacing. Evolution of minimum surface pressure (MSP) and maximum 1 km azimuthally averaged wind speed (MWS), the wind–pressure relationship, radial profiles of wind speed and surface pressure, and wind composites are presented for all participating GCMs at both horizontal grid spacings. While all TCs undergo a similar evolution process, some reach significantly higher intensities than others, ultimately impacting their horizontal and vertical structures. TCs simulated at 25 km grid spacings retain these differences but reach higher intensities and are more compact than their 50 km counterparts. These results indicate that dynamical core choice is an essential factor in GCM development, and future work should be conducted to explore how specific differences within the dynamical core affect TC behavior in GCMs.
The purpose of this paper is to emphasize the improvement of Zr-based ceramics properties as a function of addition of Ce ions in the structure of the original ceramics. The structural investigations ...proposed in this paper cover X-ray, and neutron diffraction offered the first indication of the variation of the phase composition and the structural parameters, micro-hardness measurements as well as non-destructive evaluations in order to analyze the structural properties of these materials with utmost importance in fields such as medicine, where these composite materials are used in hip-implants or dental implants/coatings. In combination of Resonant Ultrasound Spectroscopy, which makes use of the resonance frequencies corresponding to the normal vibrational modes of a solid in order to evaluate the elastic constants of the materials, we emphasize a unique approach on evaluating the physical properties of these ceramics, which could help in advancing the understanding of properties and applications in medical fields.
The egg-laying hormones (ELHs) of gastropod mollusks were characterized more than forty years ago. Yet, they have remained little explored in other mollusks. To gain insights into the functionality ...of the ELH signaling system in a bivalve mollusk - the oyster Crassostrea gigas, this study investigates the processing of its ELH precursor (Cragi-ELH) by mass spectrometry. Some of the ELH mature peptides identified in this study were subsequently investigated by nuclear magnetic resonance and shown to adopt an extended alpha-helix structure in a micellar medium mimicking the plasma membrane. To further characterize the ELH signaling system in C. gigas, a G protein-coupled receptor phylogenetically related to ecdysozoan diuretic hormone DH44 and corticotropin-releasing hormone (CRH) receptors named Cragi-ELHR was also characterized functionally and shown to be specifically activated by the two predicted mature ELH peptides and their N-terminal fragments. Both Cragi-ELH and Cragi-ELHR encoding genes were mostly expressed in the visceral ganglia (VG). Cragi-ELH expression was significantly increased in the VG of both fully mature male and female oysters at the spawning stage. When the oysters were submitted to a nutritional or hyposaline stress, no change in the expression of the ligand or receptor genes was recorded, except for Cragi-ELHR only during a mild acclimation episode to brackish water. These results suggest a role of Cragi-ELH signaling in the regulation of reproduction but not in mediating the stress response in our experimental conditions.
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