Influence of Cytokines and Autologous Lymphokine-Activated Killer Cells on Leukemic Bone Marrow Cells and Colonies in AML

We have already shown that cytokine cocktails (IL-1 beta, IL-3, IL-6, SCF, GM-CSF) and/or lymphokine-activated killer (LAK) cells can reduce the amounts of clonal, CD34-positive mononuclear bone marrow cells (BM-MNC) in acute myeloid leukemia (AML). In addition, the influence of those cocktails and/or LAK cells on the clonogenic potential of AML BM-MNC was investigated. BM colonies cultured in agar during different stages of the disease were immunophenotyped in situ: 17 patients at diagnosis, 14 patients in complete remission, 8 patients at relapse, 8 healthy donors. A significant reduction in leukemic cells and colonies positive for CD34 after in vitro culture of BM-MNC with cytokine cocktails was achieved with all samples obtained at diagnosis (n = 8, p < 0.01), in 6 of 8 cases in complete remission but only in 2 of 6 cases at relapse. Cytokine cocktails stimulated granulopoiesis as well as B and T lymphopoiesis. Colonies with leukemic phenotype could never be detected in healthy BM. A significant reduction in leukemic colonies was achieved by coculture of BM-MNC (uncultured or cytokine precultured) with autologous LAK cells in all 4 cases at diagnosis and in 1 case at relapse. An additive effect of in vitro cytokine preincubation of BM samples on the leukemia-reducing effect of LAK cells could be demonstrated in all samples studied (p <0.001; diagnosis: n = 10, relapse: n = 3, complete remission: n = 7). Patients had a better prognosis if CD34-positive colonies in AML could be reduced by cytokine incubation (p = 0.03) or coculture with autologous LAK cells in vitro (p = 0.04). Our data show that cytokines as well as LAK cells alone and in combination can reduce, however not eliminate clonogenic AML cells. Such mechanisms might be responsible for maintaining stable remissions in AML. Copyright (C) 2001 S. Karger AG, Basel

Detection of neutral hydrogen in early-type dwarf galaxies of the Sculptor Group

We present our results of deep 21 cm line (HI) observations of five early and mixed-type dwarf galaxies in the nearby Sculptor group using the ATNF 64m Parkes Radio Telescope. Four of these objects, ESO294-G010, ESO410-G005, ESO540-G030, and ESO540-G032, were detected in HI with neutral hydrogen masses in the range of 2-9x10^5 M_{\odot} ($M_{HI}/L_{B}$ = 0.08, 0.13, 0.16, and 0.18, respectively). These HI masses are consistent with the gas mass expected from stellar outflows over a large period of time. Higher resolution radio data from the Australia Telescope Compact Array were further analysed to measure more accurate positions and the distribution of the HI gas. In the cases of dwarfs ESO294-G010 and ESO540-G030, we find significant offsets of 290 pc and 460 pc, respectively, between the position of the HI peak flux and the center of the stellar component. These offsets are likely to have internal cause such as the winds from star-forming regions. The fifth object, the spatially isolated dwarf elliptical Scl-dE1, remains undetected at our 3\sigma limit of 22.5 mJy km/s and thus must contain less than 10^5 M_{\odot} of neutral hydrogen. This leaves Scl-dE1 as the only Sculptor group galaxy known where no interstellar medium has been found to date. The object joins a list of similar systems including the Local Group dwarfs Tucana and Cetus that do not fit into the global picture of the morphology-density relation where gas-rich dwarf irregulars are in relative isolation and gas-deficient dwarf ellipticals are satellites of more luminous galaxies.Comment: 21 pages, 4 figures, to be published in AJ (accepted

Gene rearrangements in bone marrow cells of patients with acute myelogenous leukemia

At diagnosis, clonal gene rearrangement probes {[}retinoic acid receptor (RAR)-alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients with secondary AML (42%). In all cases with promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n = 9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL gene were detected in 12, 10, 16 and 12% of the cases, respectively, whereas only few cases showed gene rearrangements in the M-bcr (6%) or G-CSF gene (3%). Survival of pAML patients with TcR-beta gene rearrangements was longer and survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than in patients without those rearrangements. No worse survival outcome was seen in patients with rearrangements in the MLL, Ig-JH or M-bcr gene. In remission of AML (CR), clonal gene rearrangements were detected in 23 of 48 cases (48%) if samples were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases with gene rearrangements at diagnosis showed the same kind of rearrangement at relapse of the disease (n = 12). Our data show that (1) populations with clonal gene rearrangements can be regularly detected at diagnosis, in CR and at relapse of AML. (2) Certain gene rearrangements that are detectable at diagnosis have a prognostic significance for the patients' outcome. Our results point out the significance of gene rearrangement analyses at diagnosis of AML in order to identify `poor risk' patients - independently of the karyotype. Moreover, the persistence of clonal cells in the further course of AML can be studied by gene rearrangement analysis. Copyright (C) 2000 S. Karger AG, Basel

Cohomology of Line Bundles: Applications

Massless modes of both heterotic and Type II string compactifications on compact manifolds are determined by vector bundle valued cohomology classes. Various applications of our recent algorithm for the computation of line bundle valued cohomology classes over toric varieties are presented. For the heterotic string, the prime examples are so-called monad constructions on Calabi-Yau manifolds. In the context of Type II orientifolds, one often needs to compute equivariant cohomology for line bundles, necessitating us to generalize our algorithm to this case. Moreover, we exemplify that the different terms in Batyrev's formula and its generalizations can be given a one-to-one cohomological interpretation. This paper is considered the third in the row of arXiv:1003.5217 and arXiv:1006.2392.Comment: 56 pages, 8 tables, cohomCalg incl. Koszul extension available at http://wwwth.mppmu.mpg.de/members/blumenha/cohomcalg

Microdomain Ca2+ Activation during Exocytosis in Paramecium Cells. Superposition of Local Subplasmalemmal Calcium Store Activation by Local Ca2+ Influx

In Paramecium tetraurelia, polyamine-triggered exocytosis is accompanied by the activation of Ca2+-activated currents across the cell membrane (Erxleben, C., and H. Plattner. 1994. J. Cell Biol. 127:935– 945). We now show by voltage clamp and extracellular recordings that the product of current × time (As) closely parallels the number of exocytotic events. We suggest that Ca2+ mobilization from subplasmalemmal storage compartments, covering almost the entire cell surface, is a key event. In fact, after local stimulation, Ca2+ imaging with high time resolution reveals rapid, transient, local signals even when extracellular Ca2+ is quenched to or below resting intracellular Ca2+ concentration ([Ca2+]e ⩽ [Ca2+]i). Under these conditions, quenched-flow/freeze-fracture analysis shows that membrane fusion is only partially inhibited. Increasing [Ca2+]e alone, i.e., without secretagogue, causes rapid, strong cortical increase of [Ca2+]i but no exocytosis. In various cells, the ratio of maximal vs. minimal currents registered during maximal stimulation or single exocytotic events, respectively, correlate nicely with the number of Ca stores available. Since no quantal current steps could be observed, this is again compatible with the combined occurrence of Ca2+ mobilization from stores (providing close to threshold Ca2+ levels) and Ca2+ influx from the medium (which per se does not cause exocytosis). This implies that only the combination of Ca2+ flushes, primarily from internal and secondarily from external sources, can produce a signal triggering rapid, local exocytotic responses, as requested for Paramecium defense

Quark Matter and Nuclear Collisions: A Brief History of Strong Interaction Thermodynamics

The past fifty years have seen the emergence of a new field of research in physics, the study of matter at extreme temperatures and densities. The theory of strong interactions, quantum chromodynamics (QCD), predicts that in this limit, matter will become a plasma of deconfined quarks and gluons -- the medium which made up the early universe in the first 10 microseconds after the big bang. High energy nuclear collisions are expected to produce short-lived bubbles of such a medium in the laboratory. I survey the merger of statistical QCD and nuclear collision studies for the analysis of strongly interacting matter in theory and experiment.Comment: 24 pages, 14 figures Opening Talk at the 5th Berkeley School on Collective Dynamics in High Energy Collisions, LBNL Berkeley/California, May 14 - 18, 201

New HoRRIzon: D7.3 NewHoRRIzon Social Lab Manual – Final Version

This manual guided the Social Lab team over three years through the three learning cycles of the 19 Social Labs of the NewHoRRIzon project. The document starts with a short invitation to the journey of a Social Lab, sketches thereafter some of the challenges of RRI. It continues with explaining the Social Lab and some of its key terms, and provides an overview on the Social Lab process (diagnosis, setting up, labbing), roles and tasks (participants, manager, facilitator, researcher, work package leader) as well as phases of the Social Lab. The Annex provides Literature, sample letters for invitations, generic Social Lab designs, minutes of the Social Lab Design Workshop in 2017 as well evaluation templates (Moment I, II, III, IV, V, VI)

Quarkonium Binding and Dissociation: The Spectral Analysis of the QGP

In statistical QCD, the thermal properties of the quark-gluon plasma can be determined by studying the in-medium behaviour of heavy quark bound states. The results can be applied to quarkonium production in high energy nuclear collisions, if these indeed form a fully equilibrated QGP. Modifications could arise if an initial charm excess persists in the collision evolution and causes quarkonium regeneration at hadronization.Comment: 12 pages, 7 figures; presented at the 2nd International Conference on Hard and Electromagnetic Probes of High Energy Collisions, Asilomar/California, June 9 - 15, 2006, and at the International Workshop on Heavy Quarkonium 2006, Brookhaven National Laboratory, June 27 - 30, 200

Fast, economic and simultaneous identification of clinically relevant Gram-negative species with multiplex real-time PCR

Aim: A newly designed multiplex real-time PCR (rt-PCR) was validated to detect four clinically relevant Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa). Materials & methods: Serial dilutions of genomic DNA were used to determine the limit of detection. Colony PCR was performed with isolates of the four selected species and other species as negative controls. Isolates were characterized genotypically and phenotypically to evaluate the assay. Results: Specific signals of all target genes were detected with diluted templates comprising ten genomic equivalents. Using colony rt-PCR, all isolates of the target species were identified correctly. All negative control isolates were negative. Conclusion: The genes gad, basC, khe and ecfX can reliably identify these four species via multiplex colony rt-PCR. © 2018 Daniel Weiss