TY - JOUR A1 - Edlich, Alexander A1 - Gerecke, Christian A1 - Giulbudagian, Michael A1 - Neumann, Falko A1 - Hedtrich, Sarah A1 - Schaefer-Korting, Monika A1 - Ma, Nan A1 - Calderon, Marcelo A1 - Kleuser, Burkhard T1 - Specific uptake mechanisms of well-tolerated thermoresponsive polyglycerol-based nanogels in antigen-presenting cells of the skin JF - European Journal of Pharmaceutics and Biopharmaceutics N2 - Engineered nanogels are of high value for a targeted and controlled transport of compounds due to the ability to change their chemical properties by external stimuli. As it has been indicated that nanogels possess a high ability to penetrate the stratum corneum, it cannot be excluded that nanogels interact with dermal dendritic cells, especially in diseased skin. In this study the potential crosstalk of the thermore-sponsive nanogels (tNGs) with the dendritic cells of the skin was investigated with the aim to determine the immunotoxicological properties of the nanogels. The investigated tNGs were made of dendritic polyglycerol (dPG) and poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)), as polymer conferring thermoresponsive properties. Although the tNGs were taken up, they displayed neither cytotoxic and genotoxic effects nor any induction of reactive oxygen species in the tested cells. Interestingly, specific uptake mechanisms of the tNGs by the dendritic cells were depending on the nanogels cloud point temperature (Tcp), which determines the phase transition of the nanoparticle. The study points to caveolae-mediated endocytosis as being the major tNGs uptake mechanism at 37 degrees C, which is above the Tcp of the tNGs. Remarkably, an additional uptake mechanism, beside caveolae-mediated endocytosis, was observed at 29 degrees C, which is the Tcp of the tNGs. At this temperature, which is characterized by two different states of the tNGs, macropinocytosis was involved as well. In summary, our study highlights the impact of thermoresponsivity on the cellular uptake mechanisms which has to be taken into account if the tNGs are used as a drug delivery system. KW - Dendritic cells KW - Drug delivery systems KW - Nanogel KW - Nanoparticle KW - Nanoparticle uptake KW - Nanotoxicology Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2016.12.016 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 155 EP - 163 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Serrano-Munoz, Itziar A1 - Mishurova, Tatiana A1 - Thiede, Tobias A1 - Sprengel, Maximilian A1 - Kromm, Arne A1 - Nadammal, Naresh A1 - Nolze, Gert A1 - Saliwan-Neumann, Romeo A1 - Evans, Alexander A1 - Bruno, Giovanni T1 - The residual stress in as-built laser powder bed fusion IN718 alloy as a consequence of the scanning strategy induced microstructure JF - Scientific reports N2 - The effect of two types of scanning strategies on the grain structure and build-up of Residual Stress (RS) has been investigated in an as-built IN718 alloy produced by Laser Powder Bed Fusion (LPBF). The RS state has been investigated by X-ray diffraction techniques. The microstructural characterization was performed principally by Electron Backscatter Diffraction (EBSD), where the application of a post-measurement refinement technique enables small misorientations (< 2 degrees) to be resolved. Kernel average misorientation (KAM) distributions indicate that preferably oriented columnar grains contain higher levels of misorientation, when compared to elongated grains with lower texture. The KAM distributions combined with X-ray diffraction stress maps infer that the increased misorientation is induced via plastic deformation driven by the thermal stresses, acting to self-relieve stress. The possibility of obtaining lower RS states in the build direction as a consequence of the influence of the microstructure should be considered when envisaging scanning strategies aimed at the mitigation of RS. KW - EBSD KW - components KW - deposition KW - diffraction KW - distortion KW - heat-treatment KW - mechanical properties KW - melting slm KW - superalloys KW - texture Y1 - 2020 U6 - https://doi.org/10.1038/s41598-020-71112-9 SN - 2045-2322 VL - 10 IS - 1 PB - Macmillan Publishers Limited, part of Springer Nature CY - London ER - TY - JOUR A1 - Scheller, Frieder W. A1 - Kleinjung, Frank A1 - Bier, Frank Fabian A1 - Markower, Alexander A1 - Neumann, Barbara A1 - Wollenberger, Ursula A1 - Kurochkin, Iliya N. A1 - Eremenko, Arkadi V. A1 - Barmin, Anatoli V. A1 - Klußmann, Sven A1 - Fürste, Jens-Peter A1 - Erdmann, Volker A. A1 - Mansuy, D. T1 - New recognition elements in biosensing Y1 - 1998 ER - TY - JOUR A1 - Gerecke, Christian A1 - Edlich, Alexander A1 - Giulbudagian, Michael A1 - Schumacher, Fabian A1 - Zhang, Nan A1 - Said, Andre A1 - Yealland, Guy A1 - Lohan, Silke B. A1 - Neumann, Falko A1 - Meinke, Martina C. A1 - Ma, Nan A1 - Calderon, Marcelo A1 - Hedtrich, Sarah A1 - Schaefer-Korting, Monika A1 - Kleuser, Burkhard T1 - Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes JF - Nanotoxicology N2 - Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery. KW - Drug delivery KW - nanoparticles KW - particle characterization KW - keratinocytes KW - nanotoxicology Y1 - 2017 U6 - https://doi.org/10.1080/17435390.2017.1292371 SN - 1743-5390 SN - 1743-5404 VL - 11 SP - 267 EP - 277 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Frübing, Peter A1 - Kremmer, Alexander A1 - Neumann, Werner A1 - Gerhard, Reimund A1 - Guy, I. L. T1 - Dielectric relaxation in piezo-, pyro- and ferroelectric polyamide 11 N2 - Ferroelectric polyamide 11 films were prepared by melt-quenching, cold-drawing and electrical poling. Their ferroelectricity was studied by means of dielectric-hysteresis measurements. A remnant polarisation of up to 35 mC/m(2) and a coercive field of 75 MV/m were obtained. The piezoelectric d(33) coefficient and the pyroelectric coefficient of the films are reduced by annealing just below the melting region, but remain at about 3 pC/N and 8 muC/(m(2)K), respectively, during further heat treatment. Differential scanning calorimetry (DSC), dielectric relaxation spectroscopy (DRS) and thermally stimulated depolarisation (TSD) were applied for investigating the conformational changes induced by melt-quenching, cold-drawing and annealing. The results indicate that the cold-drawn film mainly consists of a rigid amorphous phase which exhibits considerably lower conductivity, no glass transition and consequently no dielectric a relaxation. Instead, an a, relaxation is found, which is related to chain motions in regions of the rigid amorphous phase where the amide-group dipoles are not perfectly ordered. Annealing removes imperfectly ordered structures, but does not affect the ferroelectric polarisation. Therefore, it may be concluded that essentially the a, relaxation causes the thermally non-stable part of the piezo- and pyroelectricity in polyamide 11 Y1 - 2004 ER - TY - GEN A1 - Gerecke, Christian A1 - Edlich, Alexander A1 - Giulbudagian, Michael A1 - Schumacher, Fabian A1 - Zhang, Nan A1 - Said, Andre A1 - Yealland, Guy A1 - Lohan, Silke B. A1 - Neumann, Falko A1 - Meinke, Martina C. A1 - Ma, Nan A1 - Calderón, Marcelo A1 - Hedtrich, Sarah A1 - Schäfer-Korting, Monika A1 - Kleuser, Burkhard T1 - Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes N2 - Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 335 KW - Drug delivery KW - nanoparticles KW - particle characterization KW - keratinocytes KW - nanotoxicology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-395325 ER - TY - JOUR A1 - Aust, Gottfried A1 - Heinemann, Steffi A1 - Hennies, Johannes A1 - Penke, Martina A1 - Rothweiler, Monika A1 - Wimmer, Eva A1 - Hess, Markus A1 - Becker, Maryanne A1 - Ehrmann-Neuhoff, Brigitte A1 - Hamann, Elke A1 - Wachtlin, Bianka A1 - Schäfer, Blanca A1 - Würzner, Kay-Michael A1 - Heister, Julian A1 - Schroeder, Sascha A1 - Düsterhöft, Stefanie A1 - Trüggelmann, Maria A1 - Richter, Kerstin A1 - Gagarina, Natalʹja Vladimirovna A1 - Posse, Dorothea A1 - Topaj, Nathalie A1 - Acikgöz, Duygu A1 - Neumann, Charleen A1 - Baumann, Jeannine A1 - Meyer, Sarah A1 - Siegmüller, Julia A1 - Kösterke-Buchardt, Antje A1 - Jung, Kristina A1 - Jassens, Frank A1 - Golchert, Kristin A1 - Wolff von Gudenberg, Alexander A1 - Schmidt, Sabine A1 - Kisielewicz, Daria A1 - Heide, Judith A1 - Göldner, Angie A1 - Ostermann, Anja ED - Adelt, Anne ED - Fritzsche, Tom ED - Roß, Jennifer ED - Düsterhöft, Stefanie T1 - Spektrum Patholinguistik = Schwerpunktthema: Hören – Zuhören – Dazugehören : Sprachtherapie bei Hörstörungen und Cochlea-Implantat T1 - Spektrum Patholinguistik = Focus topic: hear – listen – participate : language therapy for people with hearing loss or Cochlear Implants N2 - Das Herbsttreffen Patholinguistik wird seit 2007 jährlich vom Verband für Patholinguistik e.V. (vpl) durchgeführt. Das 7. Herbsttreffen mit dem Schwerpunktthema "Hören – Zuhören – Dazugehören: Sprachtherapie bei Hörstörungen und Cochlea-Implantat" fand am 16.11.2013 in Potsdam statt. Der vorliegende Tagungsband beinhaltet die sechs Vorträge zum Schwerpunktthema aus verschiedenen Perspektiven: der medizinischen, der therapeutischen, der wissenschaftlichen sowie der von Betroffenen. Weiterhin sind die Beiträge der Posterpräsentationen zu Themen der sprachtherapeutischen Forschung und Praxis abgedruckt. N2 - The 'Herbsttreffen Patholinguistik' is an annual conference organized by the Association for Patholinguistics (Verband für Patholinguistik e.V./vpl) since 2007. The seventh edition of this event took place on November 16 2013 in Potsdam and had as its focus topic "Hear – Listen– Participate: Language Therapy for People with Hearing Loss or Cochlear Implants". These proceedings contain the keynote talks covering the medical, therapeutic, and scientific perspectives as well as the view from two users of cochlear implants. The second part comprises the contributions to the poster session from different areas of speech/language therapy research and practice. T3 - Spektrum Patholinguistik - 7 KW - Patholinguistik KW - Sprachtherapie KW - Hörstörungen KW - Cochlea-Implantat KW - Hören KW - patholinguistics KW - speech/language therapy KW - hearing loss KW - cochlear implant KW - hearing Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-70629 SN - 978-3-86956-294-0 SN - 1869-3822 SN - 1866-9433 IS - 7 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Fritsch, Tobias A1 - Sprengel, Maximilian A1 - Evans, Alexander A1 - Farahbod-Sternahl, Lena A1 - Saliwan-Neumann, Romeo A1 - Hofmann, Michael A1 - Bruno, Giovanni T1 - On the determination of residual stresses in additively manufactured lattice structures JF - Journal of applied crystallography / International Union of Crystallography N2 - The determination of residual stresses becomes more complicated with increasing complexity of the structures investigated. Additive manufacturing techniques generally allow the production of 'lattice structures' without any additional manufacturing step. These lattice structures consist of thin struts and are thus susceptible to internal stress-induced distortion and even cracks. In most cases, internal stresses remain locked in the structures as residual stress. The determination of the residual stress in lattice structures through nondestructive neutron diffraction is described in this work. It is shown how two difficulties can be overcome: (a) the correct alignment of the lattice structures within the neutron beam and (b) the correct determination of the residual stress field in a representative part of the structure. The magnitude and the direction of residual stress are discussed. The residual stress in the strut was found to be uniaxial and to follow the orientation of the strut, while the residual stress in the knots was more hydrostatic. Additionally, it is shown that strain measurements in at least seven independent directions are necessary for the estimation of the principal stress directions. The measurement directions should be chosen according to the sample geometry and an informed choice on the possible strain field. If the most prominent direction is not measured, the error in the calculated stress magnitude increases considerably. KW - additive manufacturing KW - laser powder bed fusion KW - residual stress KW - principal stress components KW - neutron diffraction KW - cellular structures KW - lattice structures Y1 - 2021 U6 - https://doi.org/10.1107/S1600576720015344 SN - 1600-5767 VL - 54 SP - 228 EP - 236 PB - Munksgaard CY - Copenhagen ER - TY - JOUR A1 - Wilhelmi, Ilka A1 - Neumann, Alexander A1 - Jähnert, Markus A1 - Ouni, Meriem A1 - Schürmann, Annette T1 - Enriched alternative splicing in islets of diabetes-susceptible mice JF - International journal of molecular sciences N2 - Dysfunctional islets of Langerhans are a hallmark of type 2 diabetes (T2D). We hypothesize that differences in islet gene expression alternative splicing which can contribute to altered protein function also participate in islet dysfunction. RNA sequencing (RNAseq) data from islets of obese diabetes-resistant and diabetes-susceptible mice were analyzed for alternative splicing and its putative genetic and epigenetic modulators. We focused on the expression levels of chromatin modifiers and SNPs in regulatory sequences. We identified alternative splicing events in islets of diabetes-susceptible mice amongst others in genes linked to insulin secretion, endocytosis or ubiquitin-mediated proteolysis pathways. The expression pattern of 54 histones and chromatin modifiers, which may modulate splicing, were markedly downregulated in islets of diabetic animals. Furthermore, diabetes-susceptible mice carry SNPs in RNA-binding protein motifs and in splice sites potentially responsible for alternative splicing events. They also exhibit a larger exon skipping rate, e.g., in the diabetes gene Abcc8, which might affect protein function. Expression of the neuronal splicing factor Srrm4 which mediates inclusion of microexons in mRNA transcripts was markedly lower in islets of diabetes-prone compared to diabetes-resistant mice, correlating with a preferential skipping of SRRM4 target exons. The repression of Srrm4 expression is presumably mediated via a higher expression of miR-326-3p and miR-3547-3p in islets of diabetic mice. Thus, our study suggests that an altered splicing pattern in islets of diabetes-susceptible mice may contribute to an elevated T2D risk. KW - alternative splicing KW - epigenetic KW - MicroRNA KW - RNAseq KW - diabetes KW - beta-cell KW - failure Y1 - 2021 U6 - https://doi.org/10.3390/ijms22168597 SN - 1422-0067 VL - 22 IS - 16 PB - Molecular Diversity Preservation International CY - Basel ER -