Isospin equilibration in relativistic heavy-ion collisions

We study the mixing and the kinetic equilibration of projectile and target nucleons in relativistic heavy-ion collisions in the energy regime between 150~AMeV and 2~AGeV in a coupled-channel BUU (CBUU) approach. We find that equilibrium in the projectile-target degrees of freedom is in general not reached even for large systems at low energy where elastic nucleon-nucleon collisions dominate. Inelastic nucleon excitations are more favorable for equilibration and their relative abundance increases both with energy and mass. Experimentally, the projectile/target admixture can be determined by measuring the degree of isospin equilibration in isospin asymmetric nuclear collisions. For one of the most promising systems currently under investigation, ${}^{96}_{44}{\rm Ru}+{}^{96}_{40}{\rm Zr}$, we investigate the influence of the equation of state and the inelastic in-medium cross section.Comment: 16 pages, 12 figures, submitted to Europ. Phys. J. A Discussion adde

Analysis of flow effects in relativistic heavy-ion collisions within the CBUU approach

We study flow phenomena in relativistic heavy-ion collisions, both in transverse and radial direction, in comparison to experimental data. The collective dynamics of the nucleus-nucleus collision is described within a transport model of the coupled channel BUU type (CBUU). This recently developed version includes all nucleonic resonances up to 1.95 GeV in mass and mean-field potentials both of the Skyrme and momentum dependent MDYI type. We find that heavy resonances play an important role in the description of transverse flow above 1 AGeV incident energy. For radial flow we analyse reaction times and equilibration and extract the parameters $T$ and $\beta$ for temperature and collective flow velocity within different prescriptions. Furthermore, we apply a coalescence model for fragment production and check the mass dependence of the flow signals.Comment: 25 pages, 17 figures, submitted to Europ. Phys. J.

Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle

Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient’s T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(−) CCR7(−) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy

Photoabsorption on nuclei

We calculate the total photoabsorption cross section on nuclei in the energy range from 300 MeV to 1 GeV within the framework of a semi-classical phase space model. Besides medium modifications like Fermi motion and Pauli blocking we focus on the collision broadening of the involved resonances. The resonance contributions to the elementary cross section are fixed by fits to partial wave amplitudes of pion photoproduction. The cross sections for $N \, R \to N \, N$, needed for the calculation of collision broadening, are obtained by detailed balance from a fit to $N \, N \to N \, N \, \pi$ cross sections. We show that a reasonable collision broadening is not able to explain the experimentally observed disappearance of the $D_{13}(1520)$-resonance in the photoabsorption cross section on nuclei.Comment: 26 pages Latex including 9 postscript figure

Photoproduction of pions and etas in nuclei

We calculate the cross sections for inclusive one-pion, two-pion and eta photoproduction in nuclei in the photon energy range from 300 MeV to 900 MeV within the framework of a semi-classical BUU transport model. Our results are compared with existing experimental data and discussed with respect to a calculation of the total photoabsorption cross section.Comment: 30 pages LaTeX including 13 postscript figure

Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia

B-cell chronic lymphocytic leukaemia (B-CLL) remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR) which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells

Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR) with an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions

Predicting meiofauna abundance to define preservation and impact zones in a deep-sea mining context using random forest modelling

There is a strong economic interest in commercial deep‐sea mining of polymetallic nodules and therefore a need to define suitable preservation zones in the abyssal plain of the Clarion Clipperton Fracture Zone (CCZ). However, besides ship‐based multibeam data, only sparse continuous environmental information is available over large geographic scales. We test the potential of modelling meiofauna abundance and diversity on high taxonomic level on large geographic scale using a random forest approach. Ship‐based multibeam bathymetry and backscatter signal are the only sources for 11 predictor variables, as well as the modelled abundance of polymetallic nodules on the seafloor. Continuous meiofauna predictions have been combined with all available environmental variables and classified into classes representing abyssal habitats using k‐means clustering. Results show that ship‐based, multibeam‐derived predictors can be used to calculate predictive models for meiofauna distribution on a large geographic scale. Predicted distribution varies between the different meiofauna response variables. To evaluate predictions, random forest regressions were additionally computed with 1,000 replicates, integrating varying numbers of sampling positions and parallel samples per site. Higher numbers of parallel samples are especially useful to smoothen the influence of the remarkable variability of meiofauna distribution on a small scale. However, a high number of sampling positions is even more important, integrating a greater amount of natural variability of environmental conditions into the model. Synthesis and applications. Polymetallic nodule exploration contractors are required to define potential mining and preservation zones within their licence area. The biodiversity and the environment of preservation zones should be representative of the sites that will be impacted by mining. Our predicted distributions of meiofauna and the derived habitat maps are an essential first step to enable the identification of areas with similar ecological conditions. In this way, it is possible to define preservation zones not only based on expert opinion and environmental proxies but also integrating evidence from the distribution of benthic communities