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Solar fertiliser production including the internal utilisation of the side-product oxygen is analysed as one promising example of an innovative process utilising renewable energy resources and addressing the aspect of integrated production – here in the case of nitrogen containing fertilisers. Alternative methods to supply solar energy into the energy intensive generation of precursors needed for nitrate-based fertiliser via the Haber Bosch and Ostwald processes are introduced. Those methods are assessed in a comparative way through process design and simulation with a focus on oxygen injection inside the NOx combustion of the Ostwald process and through calculation of its economic impacts.

Abstract Background Fluid loading-based goal-directed therapy is a cornerstone of anaesthesia management in major surgery. Its widespread application has contributed to a significant improvement in perioperative morbidity and mortality. In theory, only hypovolemic patients should receive fluid therapy. However, to achieve such a diagnosis, a surrogate marker of cardiac output adequacy must be used. Current methods of fluid loading-based goal-directed therapy do not assess cardiac output adequacy. Nowadays, new devices make it possible to continuously monitor central venous oxygen saturation (ScvO2) and therefore, to assess the adequacy of perioperative cardiac output during surgery. In major surgery, ScvO2-based goal-directed therapy can be used to enhance fluid therapy and improve patient outcomes. Methods We designed a prospective, randomised, single-blinded, multicentre controlled superiority study with a 1:1 allocation ratio. Patients to be included will be high-risk major surgery patients (> 50 years old, ASA score > 2, major intra-abdominal or intra-thoracic surgery > 90 min). Patients in the control group will undergo standard fluid loading-based goal-directed therapy, as recommended by the guidelines. Patients in the intervention group will have ScvO2-based goal-directed therapy and receive fluid loading only if fluid responsiveness and cardiac output inadequacy are present. The primary outcome will be the Comprehensive Complication Index on day five postoperatively. Discussion This study is the first to address the issue of cardiac output adequacy in goal-directed therapy. Our hypothesis is that cardiac output optimisation during major surgery achieved by continuous monitoring of the ScvO2 to guide fluid therapy will result in a reduction of postoperative complications as compared with current goal-directed fluid therapy practices. Trial registration ClinicalTrials.gov. NCT03828565. Registered on February 4, 2019.

Differences between capillary and venous glucose concentrations have been reported in the past. In continuous glucose monitoring (CGM) system performance studies, comparator measurements are often performed in venous samples, despite CGM systems typically aiming at providing capillary-like values. In this study, differences between venous, capillary and interstitial glucose concentrations, measured with a laboratory analyzer, a self-monitoring of blood glucose (SMBG) system and an intermittent-scanning CGM system were investigated in subjects without diabetes after glucose load.

The optimization of the affinity of monoclonal antibodies is crucial for the development of drug candidates, as it can impact the efficacy of the drug and, thus, the dose and dosing regimen, limit adverse effects, and reduce therapy costs. Here, we present the affinity maturation of an EGFR×PD-L1 Two-in-One antibody for EGFR binding utilizing site-directed mutagenesis and yeast surface display. The isolated antibody variants target EGFR with a 60-fold-improved affinity due to the replacement of a single amino acid in the CDR3 region of the light chain. The binding properties of the Two-in-One variants were confirmed using various methods, including BLI measurements, real-time antigen binding measurements on surfaces with a mixture of both recombinant proteins and cellular binding experiments using flow cytometry as well as real-time interaction cytometry. An AlphaFold-based model predicted that the amino acid exchange of tyrosine to glutamic acid enables the formation of a salt bridge to an arginine at EGFR position 165. This easily adaptable approach provides a strategy for the affinity maturation of bispecific antibodies with respect to the binding of one of the two antigens.

The UN sustainable development goals (SDGs) and the Paris climate target require a holistic transformation towards human well-being within planetary boundaries. However, there are growing debates on how to best pursue these targets. Proposed transformation strategies include market- and technology-driven green-growth, shifting towards a sufficiency-oriented post-growth economy, and a transformation driven primarily by strong government action. Here we quantify three alternative sustainable development pathways (SDPs), Economy-driven Innovation, Resilient Communities, and Managing the Global Commons, that reflect these different societal strategies. We compare the quantifications from two integrated assessment models and two sectoral models of the buildings and materials sectors across a broad set of indicators for sustainable development and climate action. Our global multi-scenario and multi-model analysis shows that all three SDPs enable substantial progress towards the human development goals of the SDGs. They simultaneously limit global warming and prevent further environmental degradation, with the sufficiency-oriented Resilient Communities scenario showing the lowest peak warming and lowest reliance on carbon dioxide removal as well as the largest improvements in biodiversity intactness. The SDPs also alleviate the concerns about the biogeophysical and technological feasibility of narrowly-focused climate change mitigation scenarios. However, the shifts in energy and food consumption patterns assumed in the SDPs, ranging from moderate in Economy-driven Innovation to very ambitious in Resilient Communities, also lead to increased challenges regarding socio-cultural feasibility.

Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations. This limited the possibility of simulating in vivo or clinical conditions in vitro. The presence of molecular oxygen is more important for the radiotoxicity of low-linear energy transfer (LET) radiation (e.g., X-rays) than that of high-LET carbon (12C) ions. The mechanisms responsible for 12C ions’ potential to overcome hypoxia-induced radioresistance are currently not fully understood. Therefore, the radioresistance of hypoxic A549 NSCLC cells following exposure to X-rays or 12C ions was investigated along with cell cycle progression and gene expression by maintaining hypoxia before, during and after irradiation. A549 cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h and then irradiated with X-rays (200 kV) or 12C ions (35 MeV/n, LET ~75 keV/µm). Cell survival was evaluated using colony-forming ability (CFA) assays immediately or 24 h after irradiation (late plating). DNA double-strand breaks (DSBs) were analyzed using γH2AX immunofluorescence microscopy. Cell cycle progression was determined by flow cytometry of 4′,6-diamidino-2-phenylindole-stained cells. The global transcription profile post-irradiation was evaluated by RNA sequencing. When hypoxia was maintained before, during and after irradiation, hypoxia-induced radioresistance was observed only in late plating CFA experiments. The killing efficiency of 12C ions was much higher than that of X-rays. Cell survival under hypoxia was affected more strongly by the timepoint of plating in the case of X-rays compared to 12C ions. Cell cycle arrest following irradiation under hypoxia was less pronounced but more prolonged. DSB induction and resolution following irradiation were not significantly different under normoxia and hypoxia. Gene expression response to irradiation primarily comprised cell cycle regulation for both radiation qualities and oxygen conditions. Several PI3K target genes involved in cell migration and cell motility were differentially upregulated in hypoxic cells. Hypoxia-induced radioresistance may be linked to altered cell cycle response to irradiation and PI3K-mediated changes in cell motility and migration in A549 cells rather than less DNA damage or faster repair.