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Publikation Delignification of low-energy mechanical pulp (asplund fibers) in a deep eutectic solvent system of choline chloride and lactic acid(Frontiers Research Foundation, 09.06.2021) Pérez, Alan; Fiskari, Juha; Schuur, BoeloDeep eutectic solvents (DESs) are considered as a green and environmentally benign solvent class for various applications, including delignification of biomass. One of the major challenges in the delignification of biomass by DES is attributed to the limitations in mass transfer. By subjecting wood chips to a low-energy mechanical refining, i.e., the Asplund process, the accessible surface area increases greatly, which in turn improves the mass transfer and increases the reaction rate. In this research, the DES delignification of Asplund fibers made of Norway spruce was studied as a strategy to produce papermaking fibers under mild conditions. A DES consisting of lactic acid and choline chloride was used due to its proven performance in delignification. Various operational conditions, such as temperature, time, DES-to-wood ratio, and the type of stirring were studied. A novel parameter, Q, allowed to evaluate the impact of the operational conditions on the quality of the pulp in terms of delignification degree and fiber length. The results showed that cooking temperature had the most significant effect on the pulp quality. Additionally, it was observed that cooking times between 30 and 45 min result in a pulp yield of about 50%, while fibers have a lignin content of about 14% and a fiber length of 0.6 mm. These results demonstrate that it is possible to obtain fibers of relatively good quality from DES delignification using Asplund fibers as the starting material.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Development of a new reactor concept for oxidation reactions(Hochschule für Life Sciences FHNW, 2023) Lamanna Bürkler, Patrizia; Zogg, Andreas; DSM-FirmenichOxidation reactions comprises an important class of reactions. One key commercial product in DSM – Firmenich' s portfolio contains an oxidation step using 100% O2. Oxidation reactions are highly exothermic, often operated in an organic solvent. With a possible ignition source, this will lead to a high-risk potential regarding explosion. To obtain a safe process, it is desirable to avoid an explosive atmosphere, but this will cause limitations regarding process temperature and pressure. In reactions with 100% O2, very high explosion pressures must be expected. An inherently safe mode of operation is only possible if the apparatus were constructed to be pressure shock resistant and the process temperature is kept between a certain range. The goal of this master thesis is the development of a new reactor concept for gas-liquid phase reactions with focus on oxidation reactions. Based on the design of a loop-reactor, the gaseous oxidizing agent O2 is transferred to the liquid reaction mass using membrane technology. The concept keeps the liquid phase saturated with O2, while minimizing the creation of an explosive atmosphere inside the reactor. The approach of a head space free reactor is a significantly increase of process safety while minimizing the constraints with regards to the solvent selection and process conditions.11 - Studentische ArbeitPublikation Nanofiltration-enhanced solvent extraction of scandium from TiO acid waste(American Chemical Society, 27.04.2022) Yagmurlu, Bengi; Huang, Danyu; von Arx, Oliver; Dittrich, Carsten; Constable, Edwin; Friedrich, Bernd; Hedwig, Sebastian; Lenz, MarkusScandium is a critical raw material with a technological potential to reduce transportation costs and CO2 emissions. However, global supply and market adoption are crucially impaired by the lack of high-grade Sc ores and recovery strategies. A tandem nanofiltration solvent extraction route is demonstrated to enable effective Sc recovery from real-world acid waste from the chloride TiO2 production route. The process involving several filtration stages, solvent extraction, and precipitation was optimized, ultimately producing >97% pure (NH4)3ScF6.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Magnesium sensing via LFA-1 regulates CD8+ T cell effector function(Cell Press, 2022) Lötscher, Jonas; Martí i Líndez, Adrià-Arnau; Kirchhammer, Nicole; Cribioli, Elisabetta; Giordano Attianese, Greta Maria Paola; Trefny, Marcel P.; Rothschild, Sacha I.; Strati, Paolo; Künzli, Marco; Lotter, Claudia; Schenk, Susanne H.; Dehio, Philippe; Löliger, Jordan; Litzler, Ludivine; Schreiner, David; Koch, Victoria; Page, Nicolas; Lee, Dahye; Grählert, Jasmin; Kuzmin, Dmitry; Burgener, Anne-Valérie; Merkler, Doron; Pless, Miklos; Balmer, Maria L.; Reith, Walter; Huwyler, Jörg; Irving, Melita; King, Carolyn G.; Zippelius, Alfred; Hess, Christoph; Lenz, MarkusThe relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8+ T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function. Clinically, low serum magnesium levels were associated with more rapid disease progression and shorter overall survival in CAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporates information on the composition of the microenvironment as a determinant of outside-in signaling activity. These findings conceptually link co-stimulation and nutrient sensing and point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Adaptive immune receptor repertoire (AIRR) community guide to TR and IG gene annotation(Springer, 28.05.2022) Babrak, Lmar; Marquez, Susanna; Busse, Christian; Lees, William; Miho, Enkelejda; Ohlin, Mats; Rosenfeld, Aaron; Stervbo, Ulrik; Watson, Corey; Schramm, Chaim; Langerak, Anton W.High-throughput sequencing of adaptive immune receptor repertoires (AIRR, i.e., IG and TR) has revolutionized the ability to carry out large-scale experiments to study the adaptive immune response. Since the method was first introduced in 2009, AIRR sequencing (AIRR-Seq) has been applied to survey the immune state of individuals, identify antigen-specific or immune-state-associated signatures of immune responses, study the development of the antibody immune response, and guide the development of vaccines and antibody therapies. Recent advancements in the technology include sequencing at the single-cell level and in parallel with gene expression, which allows the introduction of multi-omics approaches to understand in detail the adaptive immune response. Analyzing AIRR-seq data can prove challenging even with high-quality sequencing, in part due to the many steps involved and the need to parameterize each step. In this chapter, we outline key factors to consider when preprocessing raw AIRR-Seq data and annotating the genetic origins of the rearranged receptors. We also highlight a number of common difficulties with common AIRR-seq data processing and provide strategies to address them.04A - Beitrag SammelbandPublikation Triphenylphosphanoxid Reduktion mit Silanen(Hochschule für Life Sciences FHNW, 2022) Brodmann, Nico; Zogg, Andreas; Zogg, Andreas; DSMTriphenylphosphan (TPP) ist ein häufig genutztes Reagenz bei der Wittig-Reaktion. Dabei wird es stöchiometrisch zu Triphenylphosphanoxid (TPPO) umgewandelt, welches zum heutigen Zeitpunkt entsorgt werden muss. Eine Rückführung zu TPP ist für die Industrie von grossem Nutzen. Deshalb wurde eine Reduktion mit Silanen für eine Implementierung untersucht. Es war möglich die grössten Hindernisse dieses Vorgehens für einen Prozess zu umgehen oder zu lösen. So wurde in diesem Zusammenhang die Aufarbeitung komplett neu entworfen und alle Abfallströme für eine Rückführung bzw. Weiterverarbeitung optimiert. Zudem konnten alle Reaktionsparameter und deren Einfluss quantifiziert und verbessert werden.11 - Studentische ArbeitPublikation Nitrosamine formation and scavenging in drug products(Hochschule für Life Sciences FHNW, 2022) Ammon-Kircher, Tamara; Zogg, Andreas; NovartisNitrosamines are considered potential mutagens in the absence of toxicological data and need to be controlled in nanogram quantities in medicinal products. In the case that a medicinal product contains a primary source of vulnerable amines, it would be desirable to have an inhibitor (nitrite scavenger) of nitrosamine formation that can be added to a formulation. Wet granulation has been identified as a critical process step in drug manufacture, this was simulated in this work.The nitrosamine formation was monitored using two systems. On the one hand, an HPLC UV/VIS analysis was implemented to monitor the nitrite level, on the other hand the nitrosamine content was detected using a Triple Quadrupole LC/MS analysis. The rate constant of nitrosation was obtained by regression of measured nitrite concentrations. Based on the results, the nitrite decomposition in water at different pH and temperature should be modelled in a mathematical model like MatLab11 - Studentische ArbeitPublikation Development of a setup to study electrostatic discharges(Hochschule für Life Sciences FHNW, 2023) Brönnimann, Benedikt; Zogg, AndreasTwo glass lined reactors in a launch platform facility operated by Syngenta have been damaged during a crystallization-process of an organic compound due to electrostatic discharges. The goal of this thesis was to design and commission a unique setup to measure charges and currents generated by such suspensions in a laboratory-scale reactor. These measurements made it possible to then calculate and estimate resulting discharge energies. An improved and more sophisticated setup was then proposed for possible implementation in their own laboratories. With this novel setup, the electrostatic charging of stirred suspensions involving non conductive solvents could be accurately measured in the context of a case study that involved the suspension that led to liner damages in the production facilities of Syngenta.11 - Studentische ArbeitPublikation Methotrexate-induced liver injury is associated with oxidative stress, impaired mitochondrial respiration, and endoplasmic reticulum stress in vitro(MDPI, 01.12.2022) Schmidt, Saskia; Messner, Catherine; Gaiser, Carine; Hämmerli, Carina; Suter-Dick, LauraLow-dose methotrexate (MTX) is a standard therapy for rheumatoid arthritis due to its low cost and efficacy. Despite these benefits, MTX has been reported to cause chronic drug-induced liver injury, namely liver fibrosis. The hallmark of liver fibrosis is excessive scarring of liver tissue, triggered by hepatocellular injury and subsequent activation of hepatic stellate cells (HSCs). However, little is known about the precise mechanisms through which MTX causes hepatocellular damage and activates HSCs. Here, we investigated the mechanisms leading to hepatocyte injury in HepaRG and used immortalized stellate cells (hTERT-HSC) to elucidate the mechanisms leading to HSC activation by exposing mono- and co-cultures of HepaRG and hTERT-HSC to MTX. The results showed that at least two mechanisms are involved in MTX-induced toxicity in HepaRG: (i) oxidative stress through depletion of glutathione (GSH) and (ii) impairment of cellular respiration in a GSH-independent manner. Furthermore, we measured increased levels of endoplasmic reticulum (ER) stress in activated HSC following MTX treatment. In conclusion, we established a human-relevant in vitro model to gain mechanistical insights into MTX-induced hepatotoxicity, linked oxidative stress in HepaRG to a GSH-dependent and -independent pathway, and hypothesize that not only oxidative stress in hepatocytes but also ER stress in HSCs contribute to MTX-induced activation of HSCs.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Measures to control invasive crayfish species in Switzerland: A success story?(Frontiers, 09.12.2020) Krieg, Raphael; King, Alex; Zenker, Armin01A - Beitrag in wissenschaftlicher Zeitschrift