Hochschule für Life Sciences FHNW

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Anfangsdatum: 2022Thema: search.filters.subject.500 - Naturwissenschaften

Bereich: Suchergebnisse

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  • Vorschaubild
    Publikation
    Development of a new reactor concept for oxidation reactions
    (Hochschule für Life Sciences FHNW, 2023) Lamanna Bürkler, Patrizia; Zogg, Andreas; DSM-Firmenich
    Oxidation 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 Arbeit
  • Vorschaubild
    Publikation
    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, Markus
    Scandium 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 Zeitschrift
  • Vorschaubild
    Publikation
    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, Markus
    The 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 Zeitschrift
  • Vorschaubild
    Publikation
    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 Sammelband
  • Vorschaubild
    Publikation
    Triphenylphosphanoxid Reduktion mit Silanen
    (Hochschule für Life Sciences FHNW, 2022) Brodmann, Nico; Zogg, Andreas; Zogg, Andreas; DSM
    Triphenylphosphan (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 Arbeit
  • Vorschaubild
    Publikation
    Nitrosamine formation and scavenging in drug products
    (Hochschule für Life Sciences FHNW, 2022) Ammon-Kircher, Tamara; Zogg, Andreas; Novartis
    Nitrosamines 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 MatLab
    11 - Studentische Arbeit
  • Vorschaubild
    Publikation
    Development of a setup to study electrostatic discharges
    (Hochschule für Life Sciences FHNW, 2023) Brönnimann, Benedikt; Zogg, Andreas
    Two 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 Arbeit
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    Publikation
    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, Laura
    Low-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 Zeitschrift
  • Vorschaubild
    Publikation
    Metabolomic serum abnormalities in dogs with hepatopathies
    (Nature, 29.03.2022) Imbery, Carolin A.; Dieterle, Frank; Ottka, Claudia; Weber, Corinna; Müller, Elisabeth; Lohi, Hannes; Giger, Urs; Schlotterbeck, Götz
    Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild
    Publikation
    Using eDNA to simultaneously detect the distribution of native and invasive crayfish within an entire country
    (Elsevier, 2022) Krieg, Raphael; Weston, Anna; Zenker, Armin; King, Alex
    The introduction of invasive crayfish has led to a decline of many European native species of crayfish across their range. In this study, novel duplex assays for all crayfish occurring in Switzerland were developed. We aimed to identify the distribution of the seven species using a traditional trap surveillance method as well by collecting water samples to detect eDNA by species-specific quantitative real-time PCR. We reveal our overall experience in finding optimal field and laboratory techniques to discover the distribution and abundance of native and invasive species in order to enhance knowledge of early invasive species invasion and highlight important pockets of populations where native species remain, for implementation of conservation strategies. Using eDNA, important populations of native noble and white-clawed crayfish were revealed in multiple waters across various cantons. The successful identification of native and invasive crayfish species in Switzerland using eDNA can be applied to future nationwide projects. This method which has the ability to detect all species simultaneously across an entire country, will allow an improvement in freshwater crayfish conservation management.
    01A - Beitrag in wissenschaftlicher Zeitschrift