Nuclear Clusters as a Probe for Expansion Flow in Heavy Ion Reactions at 10-15AGeV

A phase space coalescence description based on the Wigner-function method for cluster formation in relativistic nucleus-nucleus collisions is presented. The momentum distributions of nuclear clusters d,t and He are predicted for central Au(11.6AGeV)Au and Si(14.6AGeV)Si reactions in the framework of the RQMD transport approach. Transverse expansion leads to a strong shoulder-arm shape and different inverse slope parameters in the transverse spectra of nuclear clusters deviating markedly from thermal distributions. A clear ``bounce-off'' event shape is seen: the averaged transverse flow velocities in the reaction plane are for clusters larger than for protons. The cluster yields --particularly at low $p_t$ at midrapidities-- and the in-plane (anti)flow of clusters and pions change if suitably strong baryon potential interactions are included. This allows to study the transient pressure at high density via the event shape analysis of nucleons, nucleon clusters and other hadrons.Comment: 38 pages, 9 figures, LaTeX type, eps used, subm. to Phys. Rev.

Differential Allocation of Constitutive and Induced Chemical Defenses in Pine Tree Juveniles: A Test of the Optimal Defense Theory

Optimal defense theory (ODT) predicts that the within-plant quantitative allocation of defenses is not random, but driven by the potential relative contribution of particular plant tissues to overall fitness. These predictions have been poorly tested on long-lived woody plants. We explored the allocation of constitutive and methyl-jasmonate (MJ) inducible chemical defenses in six half-sib families of Pinus radiata juveniles. Specifically, we studied the quantitative allocation of resin and polyphenolics (the two major secondary chemicals in pine trees) to tissues with contrasting fitness value (stem phloem, stem xylem and needles) across three parts of the plants (basal, middle and apical upper part), using nitrogen concentration as a proxy of tissue value. Concentration of nitrogen in the phloem, xylem and needles was found to be greater higher up the plant. As predicted by the ODT, the same pattern was found for the concentration of non-volatile resin in the stem. However, in leaf tissues the concentrations of both resin and total phenolics were greater towards the base of the plant. Two weeks after MJ application, the concentrations of nitrogen in the phloem, resin in the stem and total phenolics in the needles increased by roughly 25% compared with the control plants, inducibility was similar across all plant parts, and families differed in the inducibility of resin compounds in the stem. In contrast, no significant changes were observed either for phenolics in the stems, or for resin in the needles after MJ application. Concentration of resin in the phloem was double that in the xylem and MJ-inducible, with inducibility being greater towards the base of the stem. In contrast, resin in the xylem was not MJ-inducible and increased in concentration higher up the plant. The pattern of inducibility by MJ-signaling in juvenile P. radiata is tissue, chemical-defense and plant-part specific, and is genetically variable

A comprehensive surface proteome analysis of myeloid leukemia cell lines for therapeutic antibody development

A detailed characterization of the cell surface proteome facilitates the identification of target antigens, which can be used for the development of antibody-based therapeutics for the treatment of hematological malignancies. We have performed cell surface biotinylation of five human myeloid leukemia cell lines and normal human granulocytes, which was used for mass spectrometric analysis and allowed the identification and label-free, relative quantification of 320 membrane proteins. Several proteins exhibited a pronounced difference in expression between leukemia cell lines and granulocytes. We focused our attention on CD166/ALCAM, as this protein was strongly up-regulated on all AML cell lines and AML blasts of some patients. A human monoclonal antibody specific to CD166 (named H8) was generated using phage display technology. H8 specifically recognized AML cells in FACS analysis while demonstrating tumor targeting properties in vivo. After in vitro screening of five potent cytotoxic agents, a duocarmycin derivative was used for the preparation of an antibody-drug conjugate, which was able to kill AML cells in vitro with an IC50 of 8nM. The presented atlas of surface proteins in myeloid leukemia provides an experimental basis for the choice of target antigens, which may be used for the development of anti-AML therapeutic antibodies. BIOLOGICAL SIGNIFICANCE: The ability to discriminate between malignant and healthy, essential cells represents an important requirement for the development of armed antibodies for the therapy of hematological malignancies. Our proteomic study is, to our knowledge, the first large scale comparison of the accessible cell surface proteome of leukemia cells and normal blood cells, facilitating the choice of a suitable target for the treatment of acute myeloid leukemia (AML). An antibody drug conjugate was generated recognizing the CD166 antigen which was found to be strongly up-regulated in all AML cell lines and AML blasts of some patients. This antibody drug conjugate SIP(H8)-Duo might be further characterized in therapy experiments and might lead to a new targeted treatment option for AML

Combination of radiotherapy with the immunocytokine L19-IL2: Additive effect in a NK cell dependent tumour model

AbstractBackground and purposeRecently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses.Material and methodsIn syngeneic F9 tumour bearing 129/FvHsd mice tumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry.ResultsTumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression.ConclusionAn additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression

Project 4: productivity and sustainability of low-temperature geothermal resources

Executive Summary: Reservoir productivity and sustainability are key factors in the exploration, development and management of geothermal resources. Through 'Program 1, Project 4 - Reservoir Productivity and Sustainability' the Western Australian Geothermal Centre of Excellence (WAGCoE) has developed innovative tools, analyses, workflows and software, which facilitate the study of geothermal resource productivity and sustainability, both in the Western Australian context and for geothermal systems in general. Two new multi-disciplinary modelling workflows integrating geology, hydrogeology and reservoir engineering have been developed to assist geothermal exploration. These workflows target thermal regimes and geological structure, and were applied to evaluate geothermal potentials for targets within the Canning and the Perth basins in Western Australia. This research highlighted the great geothermal resource potential of these basins for direct-use applications. WAGCoE has originated and developed the GeoTemp™ software package to assist the processing, interpretation and modelling of temperature measurement datasets. GeoTemp™ has been used in a range of projects that have generated new understandings of the subsurface thermal characteristics of the Perth Basin and how best to exploit them sustainably. The thermal workflow assists the reservoir engineer in characterizing the thermal regime of target formations. WAGCoE has also helped CSIRO to pursue a major geothermal infrastructure project (SESKA Geothermal) in Perth to stimulate the development of large-scale use of geothermal resources in Western Australia. Together with CSIRO, WAGCoE has pioneered new resource assessment methods for shallow and deep systems, and is leading the development of a major heat rejection technology within the Perth Metropolitan Area. An innovative concept for physical manipulation of thermal fluids in situ was developed and has been submitted for international patent review. Research conducted in this Project has been widely applied to Western Australia (Canning Basin, Perth Basin, Perth Metropolitan Area, Gnangara Mound, M345 ASR trial site, and the Kensington 1 well site at the Australian Resources Research Centre). The research outcomes of this Project were presented at local, national and international conferences, and have been published in leading international scientific journals. This project also provided training to 13 Honours and MSc students, and 1 PhD student on specific technical skills and techniques that are immediately transferrable to various fields of research associated with geothermal energy and reservoir engineering