Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity

Orientation dependence of thermal and mechanical hysteresis in Ni51Fe18Ga27Co4 single crystals

The orientation dependence of thermal ΔТ and mechanical Δσ hysteresis was investigated in Ni51Fe18Ga27Co4 single crystals as-grown with isobaric (shape memory effect) and isothermal (superelasticity) experiments. Single crystals oriented along the [001]-direction show a high reversible deformation of 001 ЭПФ ε = (4,0 ± 0,2) % for martensitic transformations, small thermal hysteresis ΔТ = (22 ± 2) K and mechanical Δσ001 = (47 ± 2) МПа hysteresis, as compared with to single crystals oriented along the [110]-direction. Such orientation dependence is determined by the contribution of the L10-martensite under the εdetw in deformation of transformation

Study of 3D-growth conditions for selective area MOVPE of high aspect ratio GaN fins with non-polar vertical sidewalls

GaN fins are 3D architectures elongated in one direction parallel to the substrate surface. They have the geometry of walls with a large height to width ratio as well as small footprints. When appropriate symmetry directions of the GaN buffer are used, the sidewalls are formed by non-polar {11-20} planes, making the fins particularly suitable for many device applications like LEDs, FETs, lasers, sensors or waveguides. The influence of growth parameters like temperature, pressure, V/III ratio and total precursor flow on the fin structures is analyzed. Based on these results, a 2-temperature-step-growth was developed, leading to fins with smooth side and top facets, fast vertical growth rates and good homogeneity along their length as well as over different mask patterns. For the core-shell growth of fin LED heterostructures, the 2-temperature-step-growth shows much smoother sidewalls and less crystal defects in the InGaN QW and p-GaN shell compared to structures with cores grown in just one step. Electroluminescence spectra of the 2-temperature-step-grown fin LED are demonstrated

Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling

Tissue lectins are emerging (patho) physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition domains (CRDs) provides tools to understand the inherent specificity of the functional pairing. We here illustrate its practical implementation in the case of human tandem-repeat-type galectin-8 (Gal-8). It is termed Gal-8 (NC) due to presence of two different CRDs at the N-and C-terminal positions. Gal-8N exhibits exceptionally high affinity for 3'-sialylated/sulfated beta-galactosides. This protein is turned into a new homodimer, i. e., Gal-8 (NN), by engineering. The product maintained activity for lactose-inhibitable binding of glycans and glycoproteins. Preferential association with 3'-sialylated/sulfated (and 6-sulfated) beta-galactosides was seen by glycan-array analysis when compared to the wild-type protein, which also strongly bound to ABH-type epitopes. Agglutination of erythrocytes documented functional bivalency. This result substantiates the potential for comparative functional studies between the variant and natural Gal-8 (NC)/Gal-8N

Three Dimensional Canonical Quantum Gravity

General aspects of vielbein representation, ADM formulation and canonical quantization of gravity are reviewed using pure gravity in three dimensions as a toy model. The classical part focusses on the role of observers in general relativity, which will later be identified with quantum observers. A precise definition of gauge symmetries and a classification of inequivalent solutions of Einstein's equations in dreibein formalism is given as well. In the quantum part the construction of the physical Hilbert space is carried out explicitly for a torus and cylinder type space manifold, which has not been done so far. Some conceptual problems of quantum gravity are discussed from the point of view of an observer sitting inside the universe.Comment: 82 pages, uses LaTeX2e and PiCTe

Technocratic attitudes: a citizens’ perspective of expert decision-making

Despite repeated appointments of technocratic governments in Europe and increasing interest in technocracy, there is little knowledge regarding citizens’ attitudes towards technocracy and the idea of governance by unelected experts. This article revisits normative debates and hypothesises that technocracy and democracy stand in a negative relationship in the eyes of European citizens. It tests this alongside a series of hypotheses on technocratic attitudes combining country-level institutional characteristics with individual survey data. While findings confirm that individual beliefs about the merits of democracy influence technocratic attitudes, two additional important factors are also identified: first, levels of trust in current representative political institutions also motivate technocratic preferences; second, historical legacies, in terms of past party-based authoritarian regime experience, can explain significant cross-national variation. The implications of the findings are discussed in the broader context of citizen orientations towards government, elitism and the mounting challenges facing representative democracy

Blue and Red Light Modulates SigB-Dependent Gene Transcription, Swimming Motility and Invasiveness in Listeria monocytogenes

Background: In a number of gram-positive bacteria, including Listeria, the general stress response is regulated by the alternative sigma factor B (SigB). Common stressors which lead to the activation of SigB and the SigB-dependent regulon are high osmolarity, acid and several more. Recently is has been shown that also blue and red light activates SigB in Bacillus subtilis. Methodology/Principal Findings: By qRT-PCR we analyzed the transcriptional response of the pathogen L. monocytogenes to blue and red light in wild type bacteria and in isogenic deletion mutants for the putative blue-light receptor Lmo0799 and the stress sigma factor SigB. It was found that both blue (455 nm) and red (625 nm) light induced the transcription of sigB and SigB-dependent genes, this induction was completely abolished in the SigB mutant. The blue-light effect was largely dependent on Lmo0799, proving that this protein is a genuine blue-light receptor. The deletion of lmo0799 enhanced the red-light effect, the underlying mechanism as well as that of SigB activation by red light remains unknown. Blue light led to an increased transcription of the internalin A/B genes and of bacterial invasiveness for Caco-2 enterocytes. Exposure to blue light also strongly inhibited swimming motility of the bacteria in a Lmo0799- and SigB-dependent manner, red light had no effect there. Conclusions/Significance: Our data established that visible, in particular blue light is an important environmental signal with an impact on gene expression and physiology of the non-phototrophic bacterium L. monocytogenes. In natural environments these effects will result in sometimes random but potentially also cyclic fluctuations of gene activity, depending on the light conditions prevailing in the respective habitat

Automation of the UNICARagil Vehicles

The German research project UNICARagil is a collaboration between eight universities and six industrial partners funded by the Federal Ministry of Education and Research. It aims to develop innovative modular architectures and methods for new agile, automated vehicle concepts. This paper summarizes the automation approach of the driverless vehicle concept and its modular realization within the four demonstration vehicles to be built by the consortium. On-board each vehicle, this comprises sensor modules for environment perception and modelling, motion planning for normal driving and safe halts, as well as the respective control algorithms and base functionalities like precise localization. A control room and cloud functionalities provide off-board support to the vehicles, which are additionally addressed in this paper