ALBERT

Description: The B-cell maturation antigen (BCMA) is selectively expressed by cells of the B-lineage, including multiple myeloma (MM) cells, and constitutes a promising target for immunotherapeutic approaches. At present, BCMA is being evaluated as target for immunotherapeutic approaches, such as CAR T cells and bispecific antibodies, which have demonstrated promising results in phase I clinical trials. The utilization of cytotoxic T cells bearing T-cell receptors against BCMA constitutes an alternative promising approach to target MM cells. Therefore, the identification of BCMA-derived peptides that are naturally presented by human leukocyte antigens (HLA) and thus can serve as target structures for CD8+ T cells, is indispensable. In a previous study, we characterized the immunopeptidomic landscape of MM by mass spectrometry-based analysis of naturally presented HLA ligands from primary MM samples and MM cell lines (Walz et al., Blood, 2015). Comparative HLA peptidome profiling of the MM-derived HLA ligands versus the immunopeptidome of numerous benign samples from different tissues identified several strictly MM-associated antigens. Here, we evaluated this dataset for the presence of BCMA-derived MM-exclusive antigens and identified two HLA class I-restricted, BCMA-derived peptides in the immunopeptidome of our cohort comprising 15 primary MM samples and MM cell lines. Notably, one of these peptides showes strictly MM-associated presentation and was never detected on any benign tissues according to our extensive immunopeptidome database (135,354 HLA ligands originating from 16,626 source proteins detected in 337 samples from various benign tissues including blood, bone marrow, lung, kidney, liver, and spleen). This HLA-B*18-restricted ligand P(BCMA)B*18 is represented in 20% (3/15) of the analyzed MM immunopeptidomes. For immunological characterization of the P(BCMA)B*18 peptide, we performed in vitro artificial antigen-presenting cell-based priming experiments engaging naïve CD8+ T cells obtained from healthy volunteers (HV). Induction of tetramer-positive T-cell populations with frequencies ranging from 0.1-2.9% of viable CD8+ T cells was observed for all analyzed healthy whole blood donors, which demonstrates the immunogenicity of P(BCMA)B*18. Subsequently, we functionally characterized the induced P(BCMA)B*18-specific CD8+ T cells using intracellular cytokine staining. Upon stimulation with P(BCMA)B*18, we observed an increased IFNγ and TNF production specifically in the peptide-specific CD8+ T cells. In addition, the degranulation marker CD107a was found to be upregulated in the analyzed tetramer-positive T cells, confirming the activity of CD8+ T cells upon peptide-stimulation. Priming experiments using naïve CD8+ T cells obtained from MM patients as well as in vitro cytotoxicity assays with polyclonal peptide-specific effector T cells are presently ongoing in order to assess the capacity of P(BCMA)B*18-specific CD8+ T cells to induce antigen-specific cell lysis. Taken together, we identified a naturally presented and MM-associated, BCMA-derived peptide, which constitutes a promising target for tailored T cell-based immunotherapeutic approaches. Disclosures Salih: Several patent applications: Patents & Royalties: e.g. EP3064507A1. Kowalewski:Immatics Biotechnologies GmbH: Employment. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding.

Description: Current analyses and predictions of spatially‐explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long‐term average thermal conditions at coarse spatial resolutions only. Hence, many climate‐forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing, or cold‐air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free‐air temperatures, microclimatic ground and near‐surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near‐surface temperature data from all over the world. Currently this database contains time series from 7538 temperature sensors from 51 countries across all key biomes. The database will pave the way towards an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.

Description: A trajectory-tracking approach for a parallel kinematic manipulator with flexible links is investigated with respect to its robustness to undesired initial oscillations. For this purpose, an inverse fuzzy arithmetical scheme is presented and applied, in order to estimate allowable bounds on the initial conditions such that a certain tolerance band around the desired trajectory is not violated. The uncertainty bounds on the initial conditions obtained from this identification procedure indicate the influence of the disturbances on the tracking error, and thus also the robustness and the performance of the control scheme. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

Description: Nonspherical drops are of interest in the formation of microcapsules in life sciences like food, pharmacy, and cosmetics, agro and fine chemicals as well as material sciences. Out of many systems, particle-stabilized emulsion drops, so-called Pickering emulsions, exhibit an interesting formulation. Systems with Pickering particles applied in an excess amount were investigated. During deformation, the particles fully covered the enlarged drop interfaces and prevented its relaxation to a spherical drop shape. Nonspherical drops could be produced in simple shear flow using an adequate process routine. The production in a simple device is a promising high-throughput alternative to microfluidic devices. Nonspherical drops are of increasing interest in the formation of microcapsules in life as well as material sciences. The production of nonspherical drops in simple shear flow is demonstrated. The drops are stabilized by particles which are situated in the interface and prevent the drops' relaxation. This simple approach is a promising high-throughput alternative to microfluidic devices.

Description: In our previous study, the effects of added kaolinite on the microstructure and strength of freeze-cast composites of kaolinite platelets and silica nanoparticles were reported. This current article details the results of an investigation into the effects of the kaolinite on the microstructure and phase transformation of these materials during sintering. It is found that upon sintering at 1000°C, grain growth and phase transformation of the silica nanoparticles in the silica/kaolinite composites are hindered, and even completely inhibited, at sufficient concentrations of added kaolinite. Nonetheless, reduction in the size of the nanoparticles suggests that diffusion from silica nanoparticles to kaolinite platelets is occurring. Upon increasing the sintering temperature to 1250°C, boundaries between the two species completely disappear and new peaks are observed in the X-ray diffraction pattern of the composite that are not present in the patterns of either silica-only or kaolinite-only samples. These findings indicate that a transitioning interfacial phase forms at higher temperatures.

Description: Ocean sediment dissolved CH4 concentrations are of interest for possible climate-driven venting from sea floor hydrate decomposition, for supporting the large-scale microbial anaerobic oxidation of CH4 that holds the oceanic CH4 budget in balance, and for environmental issues of the oil and gas industry. Analyses of CH4 from recovered cores near vent locations typically show a maximum of ∼1 mM, close to the 1 atmosphere equilibrium value. We show from novel in situ measurement with a Raman-based probe that geochemically coherent profiles of dissolved CH4 occur rising to 30 mM (pCH4 = 3 MPa) or an excess pressure ∼3× greater than CO2 in a bottle of champagne. Normalization of the CH4 Raman ν1 peak to the ubiquitous water ν2 bending peak provides a fundamental internal calibration. Very large losses of CH4 and fractions of other gases (CO2, H2S) must typically occur from recovered cores at gas rich sites. The new data are consistent with observations of microbial biomass and observed CH4 oxidation rates at hydrate rich sites and support estimates of a greatly expanded near surface oceanic pore water CH4 reservoir.

Description: Abstract We report on laboratory and field Raman spectroscopy experiments on the structure of water in sea water and describe this as a function of temperature and pressure. The Raman spectrum of water/seawater is dominated by the water stretching mode band with a frequency shift in the range 2,800–3,800 cm−1. Here the hydrogen bonded (HB) clusters of several water molecules and nonhydrogen bonded (nHB, singlet H2O) forms are revealed with an isoskedastic point, similar to the isosbestic point for pH sensitive dyes. This band can be deconvolved into five Gaussian peaks, each with a specific spectroscopic assignment. We find that within the temperature range of 0–40 °C the vastly greater mass and volume of ocean water (78–85%) is in the HB forms, dominantly as (H2O)5. Without hydrogen bonding there would be no ocean, and nowhere in the bulk ocean does the simple H2O molecule exceed 20% of the total. The fraction of water molecules in the solvation shell around ions in seawater represents a third type of water, bound to an ion but not hydrogen bonded. Approximately 6% of the water molecules present at 35 salinity are in this form, and their concentration is not affected by temperature or pressure. The HB forms are a continuum of species in rapid exchange. The fraction of nHB is driven solely by temperature. We find no evidence that increased pressure changes the population of the free singlet nHB molecule; pressure drives the dominantly (H2O)5 population toward a lower volume, nested, molecular state.

Description: [1]  The ECHAM6 atmospheric general circulation model is the atmosphere component of the Max Planck Institute Earth System Model (MPI-ESM) that is used in the Coupled Model Intercomparison Project Phase 5 (CMIP5) simulations. As ECHAM6 has its uppermost layer centered at 0.01 hPa in the upper mesosphere, these simulations offer the opportunity to study the middle atmosphere climate change and its relation to the troposphere on the basis of a very comprehensive set of state-of-the-art model simulations. The goals of this paper are (a) to introduce those new features of ECHAM6 particularly relevant for the middle atmosphere, including external forcing data, and (b) to evaluate the simulated middle atmosphere and describe the simulated response to natural and anthropogenic forcings. New features in ECHAM6 with respect to ECHAM5 include a new short-wave radiation scheme, the option to vary spectral irradiance independent of total solar irradiance, and a latitude-dependent gravity-wave source strength. The description of external forcing data focuses on solar irradiance and ozone. Stratospheric temperature trends simulated with the MPI-ESM for the last decades of the 20th century agree well with observations. The future projections depend strongly on the scenario. Under the high emission scenario RCP8.5, simulated temperatures are locally lower by more than 20 K than preindustrial values. Many of the simulated patterns of the responses to natural forcings as provided by solar variability, volcanic aerosols, and El Niño–Southern Oscillation, largely agree with the observations.