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    Tuning the corona-core ratio of polyplex micelles for selective oligonucleotide delivery to hepatocytes or hepatic immune cells
    (Amsterdam [u.a.] : Elsevier Science, 2023) Foo, WanLing; Cseresnyés, Zoltán; Rössel, Carsten; Teng, Yingfeng; Ramoji, Anuradha; Chi, Mingzhe; Hauswald, Walter; Huschke, Sophie; Hoeppener, Stephanie; Popp, Jürgen; Schacher, Felix H.; Sierka, Marek; Figge, Marc Thilo; Press, Adrian T.; Bauer, Michael
    Targeted delivery of oligonucleotides or small molecular drugs to hepatocytes, the liver's parenchymal cells, is challenging without targeting moiety due to the highly efficient mononuclear phagocyte system (MPS) of the liver. The MPS comprises Kupffer cells and specialized sinusoidal endothelial cells, efficiently clearing nanocarriers regardless of their size and surface properties. Physiologically, this non-parenchymal shield protects hepatocytes; however, these local barriers must be overcome for drug delivery. Nanocarrier structural properties strongly influence tissue penetration, in vivo pharmacokinetics, and biodistribution profile. Here we demonstrate the in vivo biodistribution of polyplex micelles formed by polyion complexation of short interfering (si)RNA with modified poly(ethylene glycol)-block-poly(allyl glycidyl ether) (PEG-b-PAGE) diblock copolymer that carries amino moieties in the side chain. The ratio between PEG corona and siRNA complexed PAGE core of polyplex micelles was chemically varied by altering the degree of polymerization of PAGE. Applying Raman-spectroscopy and dynamic in silico modeling on the polyplex micelles, we determined the corona-core ratio (CCR) and visualized the possible micellar structure with varying CCR. The results for this model system reveal that polyplex micelles with higher CCR, i.e., better PEG coverage, exclusively accumulate and thus allow passive cell-type-specific targeting towards hepatocytes, overcoming the macrophage-rich reticuloendothelial barrier of the liver.
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    Comparison of novel semi-airborne electromagnetic data with multi-scale geophysical, petrophysical and geological data from Schleiz, Germany
    (Amsterdam [u.a.] : Elsevier Science, 2020) Steuer, Annika; Smirnova, Maria; Becken, Michael; Schiffler, Markus; Günther, Thomas; Rochlitz, Raphael; Yogeshwar, Pritam; Mörbe, Wiebke; Siemon, Bernhard; Costabel, Stephan; Preugschat, Benedikt; Ibs-von Seht, Malte; Zampa, Luigi Sante; Müller, Franz
    In the framework of the Deep Electromagnetic Sounding for Mineral EXploration (DESMEX) project, we carried out multiple geophysical surveys from regional to local scales in a former mining area in the state of Thuringia, Germany. We prove the applicability of newly developed semi-airborne electromagnetic (EM) systems for mineral exploration by cross-validating inversion results with those of established airborne and ground-based investigation techniques. In addition, supporting petrophysical and geological information to our geophysical measurements allowed the synthesis of all datasets over multiple scales. An initial regional-scale reconnaissance survey was performed with BGR's standard helicopter-borne geophysical system deployed with frequency-domain electromagnetic (HEM), magnetic and radiometric sensors. In addition to geological considerations, the HEM results served as base-line information for the selection of an optimal location for the intermediate-scale semi-airborne EM experiments. The semi-airborne surveys utilized long grounded transmitters and two independent airborne receiver instruments: induction coil magnetometers and SQUID sensors. Due to the limited investigation depth of the HEM method, local-scale electrical resistivity tomography (ERT) and long-offset transient electromagnetic (LOTEM) measurements were carried out on a reference profile, enabling the validation of inversion results at greater depths. The comparison of all inversion results provided a consistent overall resistivity distribution. It further confirmed that both semi-airborne receiver instruments achieve the bandwidth and sensitivity required for the investigation of the resistivity structure down to 1 km depth and therewith the detection of deeply seated earth resources. A 3D geological model, lithological and geophysical borehole logs as well as petrophysical investigations were integrated to interpret of the geophysical results. Distinct highly-conductive anomalies with resistivities of less than 10 Om were identified as alum shales over all scales. Apart from that, the petrophysical investigations exhibited that correlating geophysical and geological information using only one single parameter, such as the electrical resistivity, is hardly possible. Therefore, we developed a first approach based on clustering methods and self-organizing maps (SOMs) that allowed us to assign geological units at the surface to a given combination of geophysical and petrophysical parameters, obtained on different scales. © 2020 The Authors
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    Non-invasive prospection techniques and direct push sensing as high-resolution validation tools in wetland geoarchaeology – Artificial water supply at a Carolingian canal in South Germany?
    (Amsterdam [u.a.] : Elsevier Science, 2020) Rabiger-Völlmer, Johannes; Schmidt, Johannes; Linzen, Sven; Schneider, Michael; Werban, Ulrike; Dietrich, Peter; Wilken, Dennis; Wunderlich, Tina; Fediuk, Annika; Berg, Stefanie; Werther, Lukas; Zielhofer, Christoph
    The prospection of (geo-)archaeological sites yield important knowledge about the concept and the utilisation of pre-historical and historical infrastructure. The satisfactory conduction of classical prospection methods like archaeological excavations or geoarchaeological vibra-coring might be challenging in the case of large sites or difficult underground conditions. This is particularly problematic in wetlands featuring a high groundwater table and high compaction rates of organic layers. In this study, we provide an alternative and non- to minimal-invasive exploration approach to discover hydro-engineering structures for artificial water supply in the surrounding of a Carolingian summit canal in South Germany. The Early Medieval Fossa Carolina was intended 792/793 CE to bridge the Central European watershed between Rhine-Main and Danube catchments. As the canal was constructed as a summit canal, an artificial water supply at the highest levels seemed very likely or even obligatory. In order to explore these obligatory hydro-engineering features, we use a wide range of on-site and off-site tools in a spatial hierarchical way. Our approach includes the large-scale SQUID magnetic survey and the sighting of historical maps. Furthermore, we integrate high-resolution direct push colour logs, and subsequent vibra-coring for small-scale stratigraphical verification and sedimentological analyses. The SQUID magnetic survey and related depth models discover two pronounced linear anomalies that might represent potential artificial water inlets in the North-Eastern and Northern Sections of the canal. I) In the North-Eastern Section, direct push colour logs, vibra-coring and 14C dating provide no evidence for a Carolingian hydro-engineering feature but reveal a natural lenticular structure of Early Holocene age. II) The linear magnetic anomaly in the Northern Section can be excluded with high probability as a hydro-engineering structure as well. Here, direct push colour logs, vibra-coring, 14C dating and the comparison with a historic map reveal evidence for a historic gravel road. Thus, we have nicely verified the magnetic information but have no prove for an artificial Carolingian water inlet from the Swabian Rezat River that contradicts with assumptions of former studies. © 2020 The Authors
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    Use of polymers as wavenumber calibration standards in deep-UVRR
    (Amsterdam [u.a.] : Elsevier Science, 2022) Pistiki, Aikaterini; Ryabchykov, Oleg; Bocklitz, Thomas W.; Rösch, Petra; Popp, Jürgen
    Deep-UV resonance Raman spectroscopy (UVRR) allows the classification of bacterial species with high accuracy and is a promising tool to be developed for clinical application. For this attempt, the optimization of the wavenumber calibration is required to correct the overtime changes of the Raman setup. In the present study, different polymers were investigated as potential calibration agents. The ones with many sharp bands within the spectral range 400–1900 cm−1 were selected and used for wavenumber calibration of bacterial spectra. Classification models were built using a training cross-validation dataset that was then evaluated with an independent test dataset obtained after 4 months. Without calibration, the training cross-validation dataset provided an accuracy for differentiation above 99 % that dropped to 51.2 % after test evaluation. Applying the test evaluation with PET and Teflon calibration allowed correct assignment of all spectra of Gram-positive isolates. Calibration with PS and PEI leads to misclassifications that could be overcome with majority voting. Concerning the very closely related and similar in genome and cell biochemistry Enterobacteriaceae species, all spectra of the training cross-validation dataset were correctly classified but were misclassified in test evaluation. These results show the importance of selecting the most suitable calibration agent in the classification of bacterial species and help in the optimization of the deep-UVRR technique.
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    Diversity of methicillin-resistant coagulase-negative Staphylococcus spp. and methicillin-resistant Mammaliicoccus spp. isolated from ruminants and New World camelids
    (Amsterdam [u.a.] : Elsevier Science, 2021) Schauer, B.; Szostak, M.P.; Ehricht, R.; Monecke, S.; Feßler, A.T.; Schwarz, S.; Spergser, J.; Krametter-Frötscher, R.; Loncaric, I.
    Information about livestock carrying methicillin-resistant coagulase-negative staphylococci and mammaliicocci (MRCoNS/MRM) is scarce. The study was designed to gain knowledge of the prevalence, the phenotypic and genotypic antimicrobial resistance and the genetic diversity of MRCoNS/MRM originating from ruminants and New World camelids. In addition, a multi-locus sequence typing scheme for the characterization of Mammaliicoccus (formerly Staphylococcus) sciuri was developed. The study was conducted from April 2014 to January 2017 at the University Clinic for Ruminants and the Institute of Microbiology at the University of Veterinary Medicine Vienna. Seven hundred twenty-three nasal swabs originating from ruminants and New World camelids with and without clinical signs were examined. After isolation, MRCoNS/MRM were identified by MALDI-TOF, rpoB sequencing and typed by DNA microarray-based analysis and PCR. Antimicrobial susceptibility testing was conducted by agar disk diffusion. From all 723 nasal swabs, 189 MRCoNS/MRM were obtained. Members of the Mammaliicoccus (M.) sciuri group were predominant (M. sciuri (n = 130), followed by M. lentus (n = 43), M. fleurettii (n = 11)). In total, 158 out of 189 isolates showed phenotypically a multi-resistance profile. A seven-loci multi-locus sequence typing scheme for M. sciuri was developed. The scheme includes the analysis of internal segments of the house-keeping genes ack, aroE, ftsZ, glpK, gmk, pta1 and tpiA. In total, 28 different sequence types (STs) were identified among 92 selected M. sciuri isolates. ST1 was the most prevalent ST (n = 35), followed by ST 2 (n = 15), ST3 and ST5 (each n = 5), ST4 (n = 3), ST6, ST7, ST8, ST9, ST10 and ST11 (each n = 2).