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International audience; Large impact structures with peak rings are common landforms across the solar system, and their formation has implications for both the interior structure and thermal evolution of planetary bodies. Numerical modeling and structural studies have been used to simulate and ground truth peak-ring formative mechanisms, but the shock metamorphic record of minerals within these structures remains to be ascertained. We investigated impact-related microstructures and high-pressure phases in zircon from melt-bearing breccias, impact melt rock, and granitoid basement from the Chicxulub peak ring (Yucatán Peninsula, Mexico), sampled by the International Ocean Discovery Program (IODP)/International Continental Drilling Project (IODP-ICDP) Expedition 364 Hole M0077A. Zircon grains exhibit shock features such as reidite, zircon twins, and granular zircon including “former reidite in granular neoblastic” (FRIGN) zircon. These features record an initial high-pressure shock wave (>30 GPa), subsequent relaxation during the passage of the rarefaction wave, and a final heating and annealing stage. Our observed grain-scale deformation history agrees well with the stress fields predicted by the dynamic collapse model, as the central uplift collapsed downward-then-outward to form the peak ring. The occurrence of reidite in a large impact basin on Earth represents the first such discovery, preserved due to its separation from impact melt and rapid cooling by the resurging ocean. The coexistence of reidite and FRIGN zircon within the impact melt–bearing breccias indicates that cooling by seawater was heterogeneous. Our results provide valuable information on when different shock microstructures form and how they are modified according to their position in the impact structure, and this study further improves on the use of shock barometry as a diagnostic tool in understanding the cratering process.

Additional file 1: Table S1. Lesion change on MRI in patients with axial spondyloarthritis, baseline to Week 104; Figure S1. Cumulative probability of change in MRI structural lesion score in patients with axial spondyloarthritis for fat metaplasia (a) and ankylosis (b) over 104 weeks, average of the readers; Table S2. Pearson correlations between the baseline covariates; Table S3. Significant subset of predictors of Week 104 structural lesion change categories, from stepwise selection models (with predictors of study, sex, and Week 104 3-level ASDAS forced into model); Table S4. Significant subset of predictors of Week 104 structural lesion change categories, from stepwise selection models (with no forcing of predictors into model); Table S5. Decrease or increase in MRI structural lesions of erosion and backfill according to sustained ASDAS outcome in patients with axial spondyloarthritis, baseline to Week 104; Figure S2. Proportion of patients with axial spondyloarthritis with increase or decrease in fat metaplasia (a), and increase or decrease in ankylosis (b) according to ASDAS outcome, baseline to Week 104.

The Cretaceous-Paleogene (K-Pg) mass extinction is marked globally by elevated concentrations of iridium, emplaced by a hypervelocity impact event 66 million years ago. Here, we report new data from four independent laboratories that reveal a positive iridium anomaly within the peak-ring sequence of the Chicxulub impact structure, in drill core recovered by IODP-ICDP Expedition 364. The highest concentration of ultrafine meteoritic matter occurs in the post-impact sediments that cover the crater peak ring, just below the lowermost Danian pelagic limestone. Within years to decades after the impact event, this part of the Chicxulub impact basin returned to a relatively low-energy depositional environment, recording in unprecedented detail the recovery of life during the succeeding millennia. The iridium layer provides a key temporal horizon precisely linking Chicxulub to K-Pg boundary sections worldwide., SCOPUS: ar.j, info:eu-repo/semantics/published

23 pages; International audience; The Late Paleozoic tectono–magmatic history and basement of the Maya block are poorly understood due to the lack of exposures of coeval magmatic rocks in the region. Recently, IODP–ICDP Expedition 364 recovered drill core samples at borehole M0077A from the peak ring of the Chicxulub impact crater, offshore of the Yucatán peninsula in the Gulf of México, have been studied comprehensively. In the lowermost ~600 m of the drill core, impact–deformed granitoids, and minor felsite and dolerite dykes are intercalated with impact melts and breccias. Zircon U-Pb dating of granitoids yielded ages of around 326 ± 5 Ma, representing the first recovery of Late Paleozoic magmatic rocks from the Maya block, which could be genetically related to the convergence of Laurentia and Gondwana. The granitoids show the features of high K2O/Na2O, LaN/YbN and Sr/Y ratios, but very low Yb and Y contents, indicating an adakitic affinity. They are also characterized by slightly positive ԑNd(326Ma) of 0.17–0.68, intermediate initial 87Sr/86Sr(326Ma) of 0.7036–0.7047 and two–stage Nd model age (TDM2) of 1027–1069 Ma, which may indicate a less evolved crustal source. Thus, the adakitic granitoids were probably generated by partial melting of thickened crust, with source components similar to Neoproterozoic metagabbro in the Carolina block (Pan–African Orogeny materials) along Peri–Gondwana. Felsite dykes are shoshonitic with typical continental arc features that are sourced from a metasomatic mantle wedge by slab–fluids. Dolerite dykes display OIB–type features such as positive Nb and Ta anomalies and low ThNpm/NbNpm. In our interpretation, the Chicxulub adakitic granitoids of this study are formed by crustal anatexis due to asthenospheric upwelling resulting from slab breakoff. Through comparing sources and processes of Late Paleozoic magmatism along the Peri–Gondwanan realm, a tearing slab breakoff model may explain the discontinuous magmatism that appears to have occurred during the convergence of Laurentia and Gondwana.

T cell receptor (TCR)-based therapeutic cells and agents have emerged as a new class of effective cancer therapies. These therapies work on cells that express intracellular cancer-associated proteins by targeting peptides displayed on major histocompatibility complex receptors. However, cross-reactivities of these agents to off-target cells and tissues have resulted in serious, sometimes fatal, adverse events. We have developed a high throughput genetic platform (termed “PresentER”) that encodes MHC-I peptide minigenes for functional immunological assays and determines the reactivities of TCR-like therapeutic agents against large libraries of MHC-I ligands. In this report, we demonstrated that PresentER could be used to identify the on-and-off targets of T cells and TCR mimic antibodies using in vitro co-culture assays or binding assays. We found dozens of MHC-I ligands that were cross-reactive with two TCR mimic antibodies and two native TCRs and that were not easily predictable by other methods.

IODP-ICDP Expedition 364 Scientists complete list of expedition scientists is in Appendix A., The Chicxulub impact led to the formation of a ~ 200-km wide by ~1-km deep crater on México's Yucatán Peninsula. Over a period of hours after the impact the ocean re-entered and covered the impact basin beneath several hundred meters of water. A suite of impactites were deposited across the crater during crater formation, and by the resurge, tsunami and seiche events that followed. International Ocean Discovery Program/International Continental Scientific Drilling Program Expedition 364 drilled into the peak ring of the Chicxulub crater, and recovered ~130 m of impact deposits and a 75-cm thick, fine-grained, carbonate-rich “Transitional Unit”, above which normal marine sedimentation resumed. Here, we describe the results of analyses of the uppermost impact breccia (suevite) and the Transitional Unit, which suggests a gradual waning of energy recorded by this local K-Pg boundary sequence. The dominant depositional motif in the upper suevite and the Transitional Unit is of rapid sedimentation characterized by graded bedding, local cross bedding, and evidence of oscillatory currents. The lower Transitional Unit records the change from deposition of dominantly sand-sized to mainly silt to clay sized material with impact debris that decreases in both grain size and abundance upward. The middle part of the Transitional Unit is interrupted by a 20 cm thick soft sediment slump overlain by graded and oscillatory current cross-laminated beds. The uppermost Transitional Unit is also soft sediment deformed, contains trace fossils, and an increasing abundance of planktic foraminifer and calcareous nannoplankton survivors. The Transitional Unit, as with similar deposits in other marine target impact craters, records the final phases of impact-related sedimentation prior to resumption of normal marine conditions. Petrographic and stable isotopic analyses of carbon from organic matter provide insight into post-impact processes. δC values are between terrestrial and marine end members with fluctuations of 1–3‰. Timing of deposition of the Transitional Unit is complicated to ascertain. The repetitive normally graded laminae, both below and above the soft sediment deformed interval, record rapid deposition from currents driven by tsunami and seiches, processes that likely operated for weeks to potentially years post-impact due to subsequent continental margin collapse events. Highly siderophile element-enrichment at the top of the unit is likely from fine-grained ejecta that circulated in the atmosphere for several years prior to settling. The Transitional Unit is thus an exquisite record of the final phases of impact-related sedimentation related to one of the most consequential events in Earth history., ESP2015-65712-C5-1-R, and ESP2017-87676-C5-1-R from the Spanish Ministry of Economy and Competitiveness and Fondo Europeo de Desarrollo Regional ; With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)

International Ocean Discovery Program (IODP) Expedition 378 was designed to recover the first comprehensive set of Paleogene sedimentary sections from a transect of sites strategically positioned in the South Pacific to reconstruct key changes in oceanic and atmospheric circulation. These sites would have provided an unparalleled opportunity to add crucial new data and geographic coverage to existing reconstructions of Paleogene climate. In addition to the ~15 month postponement of Expedition 378 and subsequent port changes resulting in a reduction of the number of primary sites, testing and evaluation of the R/V JOIDES Resolution derrick in the weeks preceding the expedition determined that it would not support deployment of drill strings in excess of 2 km. Because of this determination, only 1 of the originally approved 7 primary sites was drilled. Expedition 378 recovered the first continuously cored, multiple-hole Paleogene sedimentary section from the southern Campbell Plateau at Site U1553. This high–southern latitude site builds on the legacy of Deep Sea Drilling Project (DSDP) Site 277, a single, partially spot cored hole, providing a unique opportunity to refine and augment existing reconstructions of the past ~66 My of climate history. This also includes the discovery of a new siliciclastic unit that had never been drilled before. As the world’s largest ocean, the Pacific Ocean is intricately linked to major changes in the global climate system. Previous drilling in the low-latitude Pacific Ocean during Ocean Drilling Program (ODP) Legs 138 and 199 and Integrated Ocean Drilling Program Expeditions 320 and 321 provided new insights into climate and carbon system dynamics, productivity changes across the zone of divergence, time-dependent calcium carbonate dissolution, bio- and magnetostratigraphy, the location of the Intertropical Convergence Zone, and evolutionary patterns for times of climatic change and upheaval. Expedition 378 in the South Pacific Ocean uniquely complements this work with a high-latitude perspective, especially because appropriate high-latitude records are unobtainable in the Northern Hemisphere of the Pacific Ocean. Site U1553 and the entire corpus of shore-based investigations will significantly contribute to the challenges of the “Climate and Ocean Change: Reading the Past, Informing the Future” theme of the IODP Science Plan (How does Earth’s climate system respond to elevated levels of atmospheric CO2? How resilient is the ocean to chemical perturbations?). Furthermore, Expedition 378 will provide material from the South Pacific Ocean in an area critical for high-latitude climate reconstructions spanning the Paleocene to late Oligocene.

Additional file 1. PROs by ASDAS disease activity at Week 104.

Background/Historical Perspective Availability of biologic disease-modifying antirheumatic drugs (bDMARDs) has improved clinical outcomes in rheumatoid arthritis, but it also increased the cost of treatment. Biosimilars, the regulated copies of biologic products, have a potential to reduce health care costs and expand access to treatment. However, because of a complex development process, biosimilars can be considered only those noninnovator biologics with satisfactory supporting evidence (ranging from structural to clinical), as outlined in the recommendations by the World Health Organization (WHO). In Latin America, a heterogeneous regulatory landscape and nonconsistent approval practices for biosimilars create decision-making challenges for practicing rheumatologists. Summary of Literature Most Latin American countries either have adopted or are in the process of adopting guidelines for the approval of biosimilars. However, among several marketed bDMARDs in the region, currently there are only 2 products that could be considered true biosimilars, based on the WHO criteria. The rest can be considered only intended copies, whose safety and efficacy are not fully established. One such product had to be withdrawn from the market because of safety concerns. Conclusions and Future Directions Practicing rheumatologists in Latin America need to understand the regulatory situation for biosimilars in their countries. When considering bDMARDs that are not innovator products, clinicians should use only those that have been approved according to the WHO recommendations. For clarification, local health authorities or professional associations should be contacted.

Highly expanded Cretaceous–Paleogene (K-Pg) boundary section from the Chicxulub peak ring, recovered by International Ocean Discovery Program (IODP) –International Continental Scientific Drilling Program (ICDP) Expedition 364, provides an unprecedented window into the immediate aftermath of the impact. Site M0077 includes ∼130 m of impact melt rock and suevite deposited the first day of the Cenozoic covered by Additional funding from:The European Consortium for Ocean Research Drilling (ECORD) implemented Expedition 364 with funding from the IODP and the ICDP. US participants were supported by the US Science Support Program and National Science Foundation Grants OCE 1737351, OCE 1736826, OCE 1737087, OCE 1737037, OCE 1736951, and OCE 1737199. J.O. was partially supported by Grants ESP2015-65712-C5-1-R and ESP2017-87676-C5-1-R from the Spanish Ministry of Economy and Competitiveness and Fondo Europeo de Desarrollo Regional. B.S. thanks Curtin University for an Australian Postgraduate Award. J.V.M. was funded by Natural Environment Research Council Grant NE/P005217/1. K. Grice thanks Australia Research Council for Grant DP180100982 and Australia New Zealand IODP Consortium for funding. The Vrije Universiteit Brussel group is supported by Research Foundation Flanders (FWO) and BELSPO; P.K. is an FWO PhD fellow.