Volcanic synchronization of Dome Fuji and Dome C Antarctic deep ice cores over the past 216 kyr

Abstract. Two deep ice cores, Dome Fuji (DF) and EPICA Dome C (EDC), drilled at remote dome summits in Antarctica, were synchronized to better understand their chronology. A total of 1401 volcanic tie points were identified covering the past 216 kyr. DFO2006, the chronology for the DF core characterized by strong constraining by the O2/N2 age markers, was compared with AICC2012, the chronology for 5 cores including the EDC core, and characterized by glaciological approaches combining ice flow modelling with various age markers. The age gaps between the two chronologies are within 2 kyr, except at Marine Isotope Stage (MIS) 5. DFO2006 gives ages older than AICC2012, with peak values of the gap of 4.5 and 3.1 kyr at MIS 5d and MIS 5b, respectively. Accordingly, ratios of duration DFO2006/AICC2012 are 85% at a period from the late stage of MIS 6 to MIS 5d and 114% at a period from MIS 5d to 5b. We then compared the DFO2006 with another chronology of the DF core, DFGT2006, characterized by glaciological approaches with weaker constraining by age markers. Features of the DFO2006/DFGT2006 age gaps are very similar to those of the DFO2006/AICC2012 age gaps. This fact lead us to hypothesize that a cause of the systematic DFO2006/AICC2012 age gaps at MIS 5 are associated with differences in the dating approaches. Besides, ages of speleothem records from China agreed well with DFO2006 at MIS 5c and 5d but not at MIS 5b. Thus, we hypothesize at least at MIS 5c and 5d, major sources of the gaps are systematic errors in surface mass balance estimation in the glaciological approach. Compatibility of the age markers should be carefully assessed in future. This work is a contribution to the European Project for Ice Coring in Antarctica (EPICA), a joint European Science Foundation/European Commission scientific program, funded by the European Union and by national contributions from Belgium, Denmark, France, Germany, Italy, the Netherlands, Norway, Sweden, Switzerland and the United Kingdom. This study was supported in part by a Grant-in-Aid for Scientific Research (A) (20241007) from the Japan Society for the Promotion of Science (JSPS).This is the final version of the article. It first appeared from Copernicus Publications via http://dx.doi.org/10.5194/cpd-11-407-201

Volcanic synchronization of Dome Fuji and Dome C Antarctic deep ice cores over the past 216 kyr

第6回極域科学シンポジウム[OM] 極域気水圏11月16日（月）　国立極地研究所１階交流アトリウ

Myelodysplastic syndromes: the pediatric point of view.

Myelodysplastic syndromes (MDS) are clonal disorders of the multipotent hematopoietic stem cell characterized by ineffective hematopoiesis and associated with marrow hypercellularity, increased intramedullary cell death and peripheral cytopenias of varying severity. Patients with myelodysplasia have a propensity (20% to 30% of cases) to undergo transformation into acute myeloid leakemia (AML), and a large body of evidence indicates that MDS represent steps in the multiphasic evolution of AML. Progression of the disease is characterized by expansion of the abnormal clone and inhibition of normal hematopoiesis leading to deterioration of the blood cell count and/or development of AML. MDS are relatively unusual in childhood, representing only 3% of pediatric hematological malignancies, although it has been reported that up to 17% of pediatric AML cases may have a previous myelodysplastic phase. The first systematic attempt at morphological classification of MDS was provided by the French-American-British (FAB) group. However, the FAB classification of MDS is only partially applicable in children. Some variants are extremely rare or absent (refractory anemia with ring sideroblasts and chronic myelomonocytic leukemia), and other peculiar pediatric disorders, represented by juvenile chronic myelogenous leukemia (JCML) and the monosomy 7 syndrome, are not included. Moreover, since there is a partial overlap between pediatric MDS and myeloproliferative disorders and the variants occurring in young children have rather specific features, some confusion still surrounds the nosographical definition of childhood MDS, so that none of the proposed classifications are widely accepted and used. Characteristically, some genetic conditions such as Fanconi's anemia, Shwachman's and Down's syndromes predispose to the development of MDS in childhood. The most common variants of childhood MDS are represented by JCML and the monosomy 7 syndrome, both disorders typically occurring in young children. JCML is characterized by a spontaneous growth of granulocyte-macrophage progenitors that show a striking hypersensitivity to granulocyte-macrophage colony-stimulating factor. Clinical presentation resembles that of some myeloproliferative disorders, with massive organomegaly usually not observed in the classically reported variants of MDS. Clinical features of the monosomy 7 syndrome resemble those observed in JCML and a differential diagnosis between these two entities relies upon the higher percentage of fetal hemoglobin, the more pronounced decrease in platelet count and, in some cases, the lack of the peculiar cytogenetic abnormality in the latter. With the number of children being cured of cancer constantly rising, a significant increase in secondary or chemotherapy-related myelodysplasia is being observed, and these disorders represent a formidable challenge for pediatric hematologists due to their poor response to chemotherapy. As a matter of fact, owing to their biological heterogeneity and aggressive clinical course in childhood, all MDS variants pose serious difficulties for successful management. If a compatible donor is available, allogeneic bone marrow transplantation (BMT) becomes the treatment of choice and should be performed during the early stages of the disease. Supportive therapy, differentiative treatments and low-dose chemotherapy, while valuable alternative therapeutic options in adults, have limited application in pediatric patients. The role of intensive chemotherapy and autologous BMT has not yet been clearly defined, and the use of hematopoietic growth factors does not seem to have a significant influence on the natural history of the disease. In the future, new insights into the events leading to progressive genetic changes in the clonal population and into the molecular basis of these genetic lesions could result in interesting new therapeutic approaches directed either at the oncogenes involved in the pathogenesis of the disease, or at the cytokines and/or their receptors causing the abnormal differentiation and proliferation of the myelodysplastic clone

Volcanic synchronization of Dome Fuji and Dome C Antarctic deep ice cores over the past 216 kyr

Two deep ice cores, Dome Fuji (DF) and EPICA Dome C (EDC), drilled at remote dome summits in Antarctica, were volcanically synchronized to improve our understanding of their chronologies. Within the past 216 kyr, 1401 volcanic tie points have been identified. DFO2006 is the chronology for the DF core that strictly follows O2/N2 age constraints with interpolation using an ice flow model. AICC2012 is the chronology for five cores, including the EDC core, and is characterized by glaciological approaches combining ice flow modelling with various age markers. A precise comparison between the two chronologies was performed. The age differences between them are within 2 kyr, except at Marine Isotope Stage (MIS) 5. DFO2006 gives ages older than AICC2012, with peak values of 4.5 and 3.1 kyr at MIS 5d and MIS 5b, respectively. Accordingly, the ratios of duration (AICC2012/DFO2006) range between 1.4 at MIS 5e and 0.7 at MIS 5a. When making a comparison with accurately dated speleothem records, the age of DFO2006 agrees well at MIS 5d, while the age of AICC2012 agrees well at MIS 5b, supporting their accuracy at these stages. In addition, we found that glaciological approaches tend to give chronologies with younger ages and with longer durations than age markers suggest at MIS 5d-6. Therefore, we hypothesize that the causes of the DFO2006-AICC2012 age differences at MIS 5 are (i) overestimation in surface mass balance at around MIS 5d-6 in the glaciological approach and (ii) an error in one of the O2/N2 age constraints by ∼ 3 kyr at MIS 5b. Overall, we improved our knowledge of the timing and duration of climatic stages at MIS 5. This new understanding will be incorporated into the production of the next common age scale. Additionally, we found that the deuterium signals of ice, δDice, at DF tends to lead the one at EDC, with the DF lead being more pronounced during cold periods. The lead of DF is by +710 years (maximum) at MIS 5d, -230 years (minimum) at MIS 7a and +60 to +126 years on average

The obstetric syndromes: Clinical relevance of placental hormones

Preterm delivery, preeclampsia and intrauterine growth restriction are the major diseases of pregnancy. A key role in their pathogenesis is played by the placenta, which is the source of hormones and other important regulatory molecules providing the metabolic and endocrine homeostasis of the fetal-placental unit. Since obstetric syndromes are characterized by important maternal and neonatal morbidity and mortality worldwide, numerous efforts have been made over the years to prevent and treat them. Due to their complex pathogenesis, however, the therapy is poor and not very effective. Therefore, great emphasis is currently given to the prevention of these diseases through the identification of biochemical and biophysical markers, among which placental factors play a crucial role. The increasing knowledge of the role of placental molecules can indeed lead to the development of new therapeutic and diagnostic tools. © 2013 Expert Reviews Ltd

La produzione metallurgica nel sito del Bronzo Medio e Recente di Solarolo-via Ordiere (Ravenna): aspetti della tecnologia e provenienza del rame

This study focuses on the analysis of bronze finds and other objects employed in metallurgical activities from the Middle and Recent Bronze Age site of Solarolo-via Ordiere (Ravenna, Italy) investigated between 2006 and 2019. Materials were found both in Middle and Recent Bronze Age layers, as well as from trenches/survey, and include mostly pins and daggers with typological affinities with other bronzes in Romagna and, more in general, in the central Po plain. Noteworthy is the presence of a golden spiral from the Middle Bronze Age 2 layers. The analysed artefacts also include metal fragments, bronze drops and implements involved in metallurgical activities, such as blowing pipes, tuyères and stone moulds, which imply casting and postcasting activities taking place at the settlement. Lead isotope analyses of 6 bronze samples designate the southern side of the Eastern Alps as preferential provenance of copper, except for one dagger constituted of copper plausibly originated from the ores of the Mitterberg area (Austria). Technological and experimental analyses suggest that the overall metallurgical production at Solarolo was not particularly complex. Objects were often re-used and re-adapted, as consequence of wear and fragmentation. Starting from the significant frequency of pins, we experimented the reproduction of two types of pins, documented in Northern Italy during these phases, namely “Cattaragna” and “con testa a rotolo” types. The experiments allowed a better understanding of the chaîne opératoire, from the production of stone moulds to the final refining of the surfaces

Nodal degenerations of plane curves and Galois covers

Globally irreducible nodes (i.e. nodes whose branches belong to the same irreducible component) have mild effects on the most common topological invariants of an algebraic curve. In other words, adding a globally irreducible node (simple nodal degeneration) to a curve should not change them a lot. In this paper we study the effect of nodal degeneration of curves on fundamental groups and show examples where simple nodal degenerations produce non-isomorphic fundamental groups and this can be detected in an algebraic way by means of Galois coverings.Comment: 16 pages, 3 figure

MYCN Amplification, along with Wild-Type RB1 Expression, Enhances CDK4/6 Inhibitors’ Efficacy in Neuroblastoma Cells

Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB's mutation landscape, optimizing individualized therapies is still challenging. In the context of genomic alterations, MYCN amplification is the most correlated event with poor outcomes. MYCN is involved in the regulation of several cellular mechanisms, including cell cycle. Thus, studying the influence of MYCN overexpression in the G1/S transition checkpoint of the cell cycle may unveil novel druggable targets for the development of personalized therapeutical approaches. Here, we show that high expression of E2F3 and MYCN correlate with poor prognosis in NB despite the RB1 mRNA levels. Moreover, we demonstrate through luciferase reporter assays that MYCN bypasses RB function by incrementing E2F3-responsive promoter activity. We showed that MYCN overexpression leads to RB inactivation by inducing RB hyperphosphorylation during the G1 phase through cell cycle synchronization experiments. Moreover, we generated two MYCN-amplified NB cell lines conditionally knockdown (cKD) for the RB1 gene through a CRISPRi approach. Indeed, RB KD did not affect cell proliferation, whereas cell proliferation was strongly influenced when a non-phosphorylatable RB mutant was expressed. This finding revealed the dispensable role of RB in regulating MYCN-amplified NB's cell cycle. The described genetic interaction between MYCN and RB1 provides the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression

Climate dependent contrast in surface mass balance in East Antarctica over the past 216 ka

ABSTRACTDocumenting past changes in the East Antarctic surface mass balance is important to improve ice core chronologies and to constrain the ice-sheet contribution to global mean sea-level change. Here we reconstruct past changes in the ratio of surface mass balance (SMB ratio) between the EPICA Dome C (EDC) and Dome Fuji (DF) East Antarctica ice core sites, based on a precise volcanic synchronization of the two ice cores and on corrections for the vertical thinning of layers. During the past 216 000 a, this SMB ratio, denoted SMBEDC/SMBDF, varied between 0.7 and 1.1, being small during cold periods and large during warm periods. Our results therefore reveal larger amplitudes of changes in SMB at EDC compared with DF, consistent with previous results showing larger amplitudes of changes in water stable isotopes and estimated surface temperature at EDC compared with DF. Within the last glacial inception (Marine Isotope Stages, MIS-5c and MIS-5d), the SMB ratio deviates by up to 0.2 from what is expected based on differences in water stable isotope records. Moreover, the SMB ratio is constant throughout the late parts of the current and last interglacial periods, despite contrasting isotopic trends.This is the accepted manuscript. It is currently embargoed pending publication