ALBERT

Beschreibung: We report sputtering measurements of anorthite-like material, taken to be representative of soils found in the lunar highlands, impacted by singly and multicharged ions representative of the solar wind. The ions investigated include protons, as well as singly and multicharged Ar ions (as proxies for the non-reactive heavy solar wind constituents), in the charge state range +1 to +9, at fixed solar-wind-relevant impact velocities of 165 and 310 km/s (0.25 keV/amu and 0.5 keV/amu). A quartz microbalance approach (QCM) for determination of total sputtering yields was used. The goal of the measurements was to determine the sputtering contribution of the heavy, multicharged minority solar wind constituents in comparison to that due to the dominant H + fraction. The QCM results show a yield increase of a factor of about 80 for Ar + vs H + sputtering and an enhancement by a factor of 1.67 between Ar 9+ and Ar + , which is a clear indication of a potential sputtering effect.

Beschreibung: Comproportionation reactions of rare-earth metal trihalides, RX 3 , with the respective R metal in the presence of a transition metal Z , preferably from group 8 through 10, yielded single crystals of 31 { ZR 6 } X 12 R and 22 { ZR 6 } X 10 type compounds, in most cases for the first time, especially with R = Tb, Dy, Ho, and Er. These are compared with literature entries. The crystal structures are discussed for the equal-atom pair {IrEr 6 }I 12 Er and {IrEr 6 }I 10 . In both cases, {IrEr 6 }I i 12 I a 6 cluster complexes are connected via i-i and i-a/a-i bridges, respectively, the {IrEr 6 } clusters are isolated. Band structure calculations were carried out on the LMTO-ASA level for a number of { Z Y 6 } X 10 examples; the density of states (DOS) and Crystal Orbital Hamiltonian Populations (COHP) derived therefrom exhibit strong Z– Y and Y –X bonding interactions. Most profitable are X = I and endohedral elements of sixth period atoms, especially Z = Os, Ir.

Beschreibung: Trehalose represents the main hemolymph sugar in most insects and its metabolic availability is regulated by trehalase. In this study, trehalase activity associated with the reproductive system was investigated in the insect Rhodnius prolixus, a hematophagous hemipteran vector of Chagas’ disease. A single-copy gene that encodes a membrane-bound trehalase (RpTre-2) was identified in the genome of R. prolixus. RpTre-2 deduced amino acid sequence is closely related to other insect membrane-bound trehalases. The expression of this gene was detected in all analyzed organs, including ovary, where total trehalase enzymatic activity was determined, and was highest at day 7 after blood meal. Ovary membranes showed a major trehalase specific activity, which confirmed the presence of a membrane-bound trehalase in this insect. This trehalase activity seemed not to be regulated at transcriptional level, as the expression of RpTre-2 gene in the ovary did not change over the days after feeding. Similarly, ovarian follicles at different developmental stages did not show any variation in the transcription level of this gene. The RpTre-2 kinetic parameters were also investigated. Activity was highest at pH 5.5 and followed Michaelis–Menten kinetics, with an apparent K m = 1.42 ± 0.36 mM and Vmax = 167.90 ± 12.91 nmol/mg protein/h. These data reveal the presence of a membrane-bound trehalase in R. prolixus that is active in ovary and probably takes part in the insect carbohydrate metabolism associated with the reproductive process.

Beschreibung: In this paper, we present measurements of He + and He +2 ion-induced sputtering of an anorthite-like thin film at a fixed solar-wind-relevant impact energy of ~0.5 keV/amu using a quartz crystal microbalance approach (QCM) for determination of total absolute sputtering yields. He +2 ions are the most abundant multicharged ions in the solar wind and increased sputtering by these ions in comparison to equi-velocity He + ions is expected to have the biggest effect on the overall sputtering efficiency of solar wind impact on the moon. Our measurements indicate an almost doubling of the sputtering yield for doubly charged incident He ions compared to same velocity He + impact. Using a selective sputtering model, the new QCM results presented here, together with previously published results for Ar +q ions and SRIM results for the relevant kinetic sputtering yields, the effect due to multicharged solar-wind ion impact on local near-surface modification of lunar anorthite-like soil is explored. It is shown that the multicharged solar wind component leads to a more pronounced and significant differentiation of depleted and enriched surface elements as well as a shortening of the timescale over which such surface compositional modifications might occur in astrophysical settings. In addition, to validate previous and future determinations of multicharged-ion-induced sputtering enhancement for those cases where the QCM approach can’t be used, relative quadrupole-mass-spectrometry (QMS) based measurements are presented for the same anorthite-like thin film as were investigated by QCM, and their suitability and limitations for charge-state-enhanced yield measurements are discussed.

Beschreibung: Approximately 25% of childhood acute lymphoblastic leukemias carry the ETV6/RUNX1 fusion gene. Despite their excellent initial treatment response, up to 20% of patients relapse. To gain insight into the relapse mechanisms, we analyzed single nucleotide polymorphism arrays for DNA copy number aberrations (CNAs) in 18 matched diagnosis and relapse leukemias. CNAs were more abundant at relapse than at diagnosis (mean 12.5 vs 7.5 per case; P = .01) with 5.3 shared on average. Their patterns revealed a direct clonal relationship with exclusively new aberrations at relapse in only 21.4%, whereas 78.6% shared a common ancestor and subsequently acquired distinct CNA. Moreover, we identified recurrent, mainly nonoverlapping deletions associated with glucocorticoid-mediated apoptosis targeting the Bcl2 modifying factor (BMF) (n = 3), glucocorticoid receptor NR3C1 (n = 4), and components of the mismatch repair pathways (n = 3). Fluorescence in situ hybridization screening of additional 24 relapsed and 72 nonrelapsed ETV6/RUNX1-positive cases demonstrated that BMF deletions were significantly more common in relapse cases (16.6% vs 2.8%; P = .02). Unlike BMF deletions, which were always already present at diagnosis, NR3C1 and mismatch repair aberrations prevailed at relapse. They were all associated with leukemias, which poorly responded to treatment. These findings implicate glucocorticoid-associated drug resistance in ETV6/RUNX1-positive relapse pathogenesis and therefore might help to guide future therapies.

Beschreibung: Abstract 1214 Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children. Typically, external triggers as infections or vaccinations cause the rise of antibodies that crossreact with antigens expressed on the platelet surface. These anti-platelet antibodies are mostly directed against glycoprotein complexes GPIIb/IIIa or GPIb/IX/V, resulting in an increased turnover of antibody-decorated platelets which are then sequestered by the reticuloendothelial system. Recently, it has been suggested that thrombocytopenia might also be due to an insufficient platelet production as serum of some patients with ITP can impair the maturation of CD34+ hematopoietic stem cells to bone marrow megakaryocytes (MKs) in vitro or abrogate the formation of proplatelets in an in vitro culture system. The accelerated platelet turnover demands the generation of platelets de novo. Bone marrow smears often reveal normal or slightly increased MKs, although they seem to be smaller and of altered morphology. However, very little is known about the consequences of anti-platelet antibodies on bone marrow MKs in vivo and in situ. Here, we took advantage of a simple animal model of passive ITP by single or multiple intraperitoneal injections of an anti-GPIb antibody into mice. MKs were evaluated by multi-color immunofluorescence histology on whole femur sections in a modified staining procedure that bypasses decalcification. MK numbers on day 3 were doubled in response to a single injection and tripled on day 8 when mice were injected additionally on day 3 and 7. In these mice platelet counts were up to 2000/nL on day 10, indicating the power to produce platelets. MK area per section was transiently upregulated on day 3 in single injected mice and quadrupled after multiple injections on day 8 before shrinking below norm on day 14. Staining with an anti-rat IgG antibody showed that the antibody was present on MKs within the bone marrow several hours to days after injection. The signal was present for 5 days and no antibody was detected on day 7. MKs had an overall normal morphology and showed no signs of apoptosis or DNA blebbing. All MKs analyzed were negative for TdT in a classical TUNEL assay, indicating that there were no single strand breaks. As platelet counts rose markedly while the antibody was still present on the MK surface, we sought to identify whether the pool of MKs is expanded or formed de novo. To address this, mice where fed with nucleotide analogue EdU for up to 12 days and femur sections stained with Click-It-647 reagent to stain for newly incorporated DNA while mice were treated with anti-platelet antibody or isotype control. We found EdU-positive MKs after 12 days in control isotype-injected mice indicating the de novo formation from hematopoietic stem cells. In antibody-injected mice, newly formed MKs were negative or stained weakly for EdU on day 12, suggesting that they arise partially from an existing pool of progenitors. Finally, we analyzed platelet formation in vivo by imaging of the cranial bone marrow of GPIIb-eYFP-heterozygous mice. The depletion antibody was labeled with Atto-590-fluorophore and injected hours before imaging. Vasculature was counterstained by Quantum dots. We found that MKs residing at the bone marrow were decorated with the antibody and released pre- and proplatelets into the vasculature, indicating that platelet biogenesis can occur in the presence of anti-platelet antibodies on MKs. Our data thus provide novel insight into the pathomechanism of platelet production in patients with ITP. Disclosures: No relevant conflicts of interest to declare.