Forcing of stratospheric chemistry and dynamics during the Dalton Minimum

The response of atmospheric chemistry and dynamics to volcanic eruptions and to a decrease in solar activity during the Dalton Minimum is investigated with the fully coupled atmosphere–ocean chemistry general circulation model SOCOL-MPIOM (modeling tools for studies of SOlar Climate Ozone Links-Max Planck Institute Ocean Model) covering the time period 1780 to 1840 AD. We carried out several sensitivity ensemble experiments to separate the effects of (i) reduced solar ultra-violet (UV) irradiance, (ii) reduced solar visible and near infrared irradiance, (iii) enhanced galactic cosmic ray intensity as well as less intensive solar energetic proton events and auroral electron precipitation, and (iv) volcanic aerosols. The introduced changes of UV irradiance and volcanic aerosols significantly influence stratospheric dynamics in the early 19th century, whereas changes in the visible part of the spectrum and energetic particles have smaller effects. A reduction of UV irradiance by 15%, which represents the presently discussed highest estimate of UV irradiance change caused by solar activity changes, causes global ozone decrease below the stratopause reaching as much as 8% in the midlatitudes at 5 hPa and a significant stratospheric cooling of up to 2°C in the mid-stratosphere and to 6°C in the lower mesosphere. Changes in energetic particle precipitation lead only to minor changes in the yearly averaged temperature fields in the stratosphere. Volcanic aerosols heat the tropical lower stratosphere, allowing more water vapour to enter the tropical stratosphere, which, via HOx reactions, decreases upper stratospheric and mesospheric ozone by roughly 4%. Conversely, heterogeneous chemistry on aerosols reduces stratospheric NOx, leading to a 12% ozone increase in the tropics, whereas a decrease in ozone of up to 5% is found over Antarctica in boreal winter. The linear superposition of the different contributions is not equivalent to the response obtained in a simulation when all forcing factors are applied during the Dalton Minimum (DM) – this effect is especially well visible for NOx/NOy. Thus, this study also shows the non-linear behaviour of the coupled chemistry-climate system. Finally, we conclude that especially UV and volcanic eruptions dominate the changes in the ozone, temperature and dynamics while the NOx field is dominated by the energetic particle precipitation. Visible radiation changes have only very minor effects on both stratospheric dynamics and chemistry

Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL–USP2 fusions

Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq: PQ-2017#305529/2017-0Deutsche Forschungsgemeinschaft, DFG: MA 1876/12-1Alexander von Humboldt-Stiftung: 88881.136091/2017-01RVO-VFN64165, 26/203.214/20172018.070.1Associazione Italiana per la Ricerca sul Cancro, AIRC: IG2015, 17593Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPESCancer Australia: PdCCRS1128727CancerfondenBarncancerfondenVetenskapsrÃ¥det, VRCrafoordska StiftelsenKnut och Alice Wallenbergs StiftelseLund University Medical Faculty FoundationXiamen University, XMU2014S0617-74-30019C7838/A15733Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNSF: 31003A_140913CNIBInstitut National Du Cancer, INCaR01 NCI CA167824National Institutes of Health, NIH: S10OD0185222016/2017, 02R/2016AU 525/1-1Deutschen Konsortium für Translationale Krebsforschung, DKTK70112951Smithsonian Institution, SIIsrael Science Foundation, ISFAustrian Science Fund, FWF: W1212SFB-F06107, SFB-F06105Acknowledgements BAL received a fellowship provided by CAPES and the Alexander von Humboldt Foundation (#88881.136091/2017-01). ME is supported by CNPq (PQ-2017#305529/2017-0) and FAPERJ-JCNE (#26/203.214/2017) research scholarships, and ZZ by grant RVO-VFN64165. GC is supported by the AIRC Investigator grant IG2015 grant no. 17593 and RS by Cancer Australia grant PdCCRS1128727. This work was supported by grants to RM from the “Georg und Franziska Speyer’sche Hochsschulstiftung”, the “Wilhelm Sander foundation” (grant 2018.070.1) and DFG grant MA 1876/12-1.Acknowledgements This work was supported by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, The Knut and Alice Wallenberg Foundation, BioCARE, The Crafoord Foundation, The Per-Eric and Ulla Schyberg Foundation, The Nilsson-Ehle Donations, The Wiberg Foundation, and Governmental Funding of Clinical Research within the National Health Service. Work performed at the Center for Translational Genomics, Lund University has been funded by Medical Faculty Lund University, Region Skåne and Science for Life Laboratory, Sweden.Acknowledgements This work was supported by the Fujian Provincial Natural Science Foundation 2016S016 China and Putian city Natural Science Foundation 2014S06(2), Fujian Province, China. Alexey Ste-panov and Alexander Gabibov were supported by Russian Scientific Foundation project No. 17-74-30019. Jinqi Huang was supported by a doctoral fellowship from Xiamen University, China.Acknowledgments This work was supported by the Swiss National Science Foundation (grant 31003A_140913; OH) and the Cancer Research UK Experimental Cancer Medicine Centre Network, Cardiff ECMCI, grant C7838/A15733. We thank N. Carpino for the Sts-1/2 double-KO mice.Acknowledgements This work was supported by the French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.We are indebted to all members of our groups for useful discussions and for their critical reading of the manuscript. Special thanks go to Silke Furlan, Friederike Opitz and Bianca Killing. F.A. is supported by the Deutsche For-schungsgemeinschaft (DFG, AU 525/1-1). J.H. has been supported by the German Children’s Cancer Foundation (Translational Oncology Program 70112951), the German Carreras Foundation (DJCLS 02R/2016), Kinderkrebsstiftung (2016/2017) and ERA PerMed GEPARD. Support by Israel Science Foundation, ERA-NET and Science Ministry (SI). A. B. is supported by the German Consortium of Translational Cancer Research, DKTK. We are grateful to the Jülich Supercomputing Centre at the Forschungszemtrum Jülich for granting computing time on the supercomputer JURECA (NIC project ID HKF7) and to the “Zentrum für Informations-und Medientechnologie” (ZIM) at the Heinrich Heine University Düsseldorf for providing computational support to H. G. The study was performed in the framework of COST action CA16223 “LEGEND”.Funding The work was supported by the Austrian Science Fund FWF grant SFB-F06105 to RM and SFB-F06107 to VS and FWF grant W1212 to VS

The KMT2A recombinome of acute leukemias in 2023

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.publishedVersionPeer reviewe

Stratospheric aerosol - Observations, processes, and impact on climate

Interest in stratospheric aerosol and its role in climate have increased over the last decade due to the observed increase in stratospheric aerosol since 2000 and the potential for changes in the sulfur cycle induced by climate change. This review provides an overview about the advances in stratospheric aerosol research since the last comprehensive assessment of stratospheric aerosol was published in 2006. A crucial development since 2006 is the substantial improvement in the agreement between in situ and space-based inferences of stratospheric aerosol properties during volcanically quiescent periods. Furthermore, new measurement systems and techniques, both in situ and space based, have been developed for measuring physical aerosol properties with greater accuracy and for characterizing aerosol composition. However, these changes induce challenges to constructing a long-term stratospheric aerosol climatology. Currently, changes in stratospheric aerosol levels less than 20% cannot be confidently quantified. The volcanic signals tend to mask any nonvolcanically driven change, making them difficult to understand. While the role of carbonyl sulfide as a substantial and relatively constant source of stratospheric sulfur has been confirmed by new observations and model simulations, large uncertainties remain with respect to the contribution from anthropogenic sulfur dioxide emissions. New evidence has been provided that stratospheric aerosol can also contain small amounts of nonsulfate matter such as black carbon and organics. Chemistry-climate models have substantially increased in quantity and sophistication. In many models the implementation of stratospheric aerosol processes is coupled to radiation and/or stratospheric chemistry modules to account for relevant feedback processes

Advancements in decadal climate predictability: the role of nonoceanic drivers

We review recent progress in understanding the role of sea ice, land surface, stratosphere, and aerosols in decadal-scale predictability and discuss the perspectives for improving the predictive capabilities of current Earth system models (ESMs). These constituents have received relatively little attention because their contribution to the slow climatic manifold is controversial in comparison to that of the large heat capacity of the oceans. Furthermore, their initialization as well as their representation in state-of-the-art climate models remains a challenge. Numerous extraoceanic processes that could be active over the decadal range are proposed. Potential predictability associated with the aforementioned, poorly represented, and scarcely observed constituents of the climate system has been primarily inspected through numerical simulations performed under idealized experimental settings. The impact, however, on practical decadal predictions, conducted with realistically initialized full-fledged climate models, is still largely unexploited. Enhancing initial-value predictability through an improved model initialization appears to be a viable option for land surface, sea ice, and, marginally, the stratosphere. Similarly, capturing future aerosol emission storylines might lead to an improved representation of both global and regional short-term climatic changes. In addition to these factors, a key role on the overall predictive ability of ESMs is expected to be played by an accurate representation of processes associated with specific components of the climate system. These act as “signal carriers,” transferring across the climatic phase space the information associated with the initial state and boundary forcings, and dynamically bridging different (otherwise unconnected) subsystems. Through this mechanism, Earth system components trigger low-frequency variability modes, thus extending the predictability beyond the seasonal scale

The impacts of volcanic aerosol on stratospheric ozone and the Northern Hemisphere polar vortex: separating radiative-dynamical changes from direct effects due to enhanced aerosol heterogeneous chemistry

After major volcanic eruptions the enhanced aerosol causes ozone changes due to greater heterogeneous chemistry on the particle surfaces (HET-AER) and from dynamical effects related to the radiative heating of the lower stratosphere (RAD-DYN). We carry out a series of experiments with an atmosphere–ocean–chemistry–climate model to assess how these two processes change stratospheric ozone and Northern Hemispheric (NH) polar vortex dynamics. Ensemble simulations are performed under present day and preindustrial conditions, and with aerosol forcings representative of different eruption strength, to investigate changes in the response behaviour. We show that the halogen component of the HET-AER effect dominates under present-day conditions with a global reduction of ozone (−21 DU for the strongest eruption) particularly at high latitudes, whereas the HET-AER effect increases stratospheric ozone due to N2O5 hydrolysis in a preindustrial atmosphere (maximum anomalies +4 DU). The halogen-induced ozone changes in the present-day atmosphere offset part of the strengthening of the NH polar vortex during mid-winter (reduction of up to −16 m s-1 in January) and slightly amplify the dynamical changes in the polar stratosphere in late winter (+11 m s-1 in March). The RAD-DYN mechanism leads to positive column ozone anomalies which are reduced in a present-day atmosphere by amplified polar ozone depletion (maximum anomalies +12 and +18 DU for present day and preindustrial, respectively). For preindustrial conditions, the ozone response is consequently dominated by RAD-DYN processes, while under present-day conditions, HET-AER effects dominate. The dynamical response of the stratosphere is dominated by the RAD-DYN mechanism showing an intensification of the NH polar vortex in winter (up to +10 m s-1 in January). Ozone changes due to the RAD-DYN mechanism slightly reduce the response of the polar vortex after the eruption under present-day conditions

Impact of a potential 21st century “grand solar minimum” on surface temperatures and stratospheric ozone

We investigate the effects of a recently proposed 21st century Dalton minimum like decline of solar activity on the evolution of Earth's climate and ozone layer. Three sets of two member ensemble simulations, radiatively forced by a midlevel emission scenario (Intergovernmental Panel on Climate Change RCP4.5), are performed with the atmosphere-ocean chemistry-climate model AOCCM SOCOL3-MPIOM, one with constant solar activity, the other two with reduced solar activity and different strength of the solar irradiance forcing. A future grand solar minimum will reduce the global mean surface warming of 2 K between 1986–2005 and 2081–2100 by 0.2 to 0.3 K. Furthermore, the decrease in solar UV radiation leads to a significant delay of stratospheric ozone recovery by 10 years and longer. Therefore, the effects of a solar activity minimum, should it occur, may interfere with international efforts for the protection of global climate and the ozone layer