@article{EdlichGereckeGiulbudagianetal.2016, author = {Edlich, Alexander and Gerecke, Christian and Giulbudagian, Michael and Neumann, Falko and Hedtrich, Sarah and Schaefer-Korting, Monika and Ma, Nan and Calderon, Marcelo and Kleuser, Burkhard}, title = {Specific uptake mechanisms of well-tolerated thermoresponsive polyglycerol-based nanogels in antigen-presenting cells of the skin}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.12.016}, pages = {155 -- 163}, year = {2016}, abstract = {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.}, language = {en} } @article{SerranoMunozMishurovaThiedeetal.2020, author = {Serrano-Munoz, Itziar and Mishurova, Tatiana and Thiede, Tobias and Sprengel, Maximilian and Kromm, Arne and Nadammal, Naresh and Nolze, Gert and Saliwan-Neumann, Romeo and Evans, Alexander and Bruno, Giovanni}, title = {The residual stress in as-built laser powder bed fusion IN718 alloy as a consequence of the scanning strategy induced microstructure}, series = {Scientific reports}, volume = {10}, journal = {Scientific reports}, number = {1}, publisher = {Macmillan Publishers Limited, part of Springer Nature}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-020-71112-9}, pages = {15}, year = {2020}, abstract = {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.}, language = {en} } @article{SchellerKleinjungBieretal.1998, author = {Scheller, Frieder W. and Kleinjung, Frank and Bier, Frank Fabian and Markower, Alexander and Neumann, Barbara and Wollenberger, Ursula and Kurochkin, Iliya N. and Eremenko, Arkadi V. and Barmin, Anatoli V. and Klußmann, Sven and F{\"u}rste, Jens-Peter and Erdmann, Volker A. and Mansuy, D.}, title = {New recognition elements in biosensing}, year = {1998}, language = {en} } @article{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calderon, Marcelo and Hedtrich, Sarah and Schaefer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, series = {Nanotoxicology}, volume = {11}, journal = {Nanotoxicology}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1743-5390}, doi = {10.1080/17435390.2017.1292371}, pages = {267 -- 277}, year = {2017}, abstract = {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.}, language = {en} } @article{FruebingKremmerNeumannetal.2004, author = {Fr{\"u}bing, Peter and Kremmer, Alexander and Neumann, Werner and Gerhard, Reimund and Guy, I. L.}, title = {Dielectric relaxation in piezo-, pyro- and ferroelectric polyamide 11}, year = {2004}, abstract = {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}, language = {en} } @misc{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calder{\´o}n, Marcelo and Hedtrich, Sarah and Sch{\"a}fer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-395325}, pages = {11}, year = {2017}, abstract = {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.}, language = {en} } @misc{AustHeinemannHenniesetal.2014, author = {Aust, Gottfried and Heinemann, Steffi and Hennies, Johannes and Penke, Martina and Rothweiler, Monika and Wimmer, Eva and Hess, Markus and Becker, Maryanne and Ehrmann-Neuhoff, Brigitte and Hamann, Elke and Wachtlin, Bianka and Sch{\"a}fer, Blanca and W{\"u}rzner, Kay-Michael and Heister, Julian and Schroeder, Sascha and D{\"u}sterh{\"o}ft, Stefanie and Tr{\"u}ggelmann, Maria and Richter, Kerstin and Gagarina, Natalʹja Vladimirovna and Posse, Dorothea and Topaj, Nathalie and Acikg{\"o}z, Duygu and Neumann, Charleen and Baumann, Jeannine and Meyer, Sarah and Siegm{\"u}ller, Julia and K{\"o}sterke-Buchardt, Antje and Jung, Kristina and Jassens, Frank and Golchert, Kristin and Wolff von Gudenberg, Alexander and Schmidt, Sabine and Kisielewicz, Daria and Heide, Judith and G{\"o}ldner, Angie and Ostermann, Anja}, title = {Spektrum Patholinguistik = Schwerpunktthema: H{\"o}ren - Zuh{\"o}ren - Dazugeh{\"o}ren : Sprachtherapie bei H{\"o}rst{\"o}rungen und Cochlea-Implantat}, number = {7}, editor = {Adelt, Anne and Fritzsche, Tom and Roß, Jennifer and D{\"u}sterh{\"o}ft, Stefanie}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, organization = {Verband f{\"u}r Patholinguistik e. V.}, isbn = {978-3-86956-294-0}, issn = {1869-3822}, doi = {10.25932/publishup-6848}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-70629}, year = {2014}, abstract = {Das Herbsttreffen Patholinguistik wird seit 2007 j{\"a}hrlich vom Verband f{\"u}r Patholinguistik e.V. (vpl) durchgef{\"u}hrt. Das 7. Herbsttreffen mit dem Schwerpunktthema "H{\"o}ren - Zuh{\"o}ren - Dazugeh{\"o}ren: Sprachtherapie bei H{\"o}rst{\"o}rungen und Cochlea-Implantat" fand am 16.11.2013 in Potsdam statt. Der vorliegende Tagungsband beinhaltet die sechs Vortr{\"a}ge zum Schwerpunktthema aus verschiedenen Perspektiven: der medizinischen, der therapeutischen, der wissenschaftlichen sowie der von Betroffenen. Weiterhin sind die Beitr{\"a}ge der Posterpr{\"a}sentationen zu Themen der sprachtherapeutischen Forschung und Praxis abgedruckt.}, language = {de} } @article{FritschSprengelEvansetal.2021, author = {Fritsch, Tobias and Sprengel, Maximilian and Evans, Alexander and Farahbod-Sternahl, Lena and Saliwan-Neumann, Romeo and Hofmann, Michael and Bruno, Giovanni}, title = {On the determination of residual stresses in additively manufactured lattice structures}, series = {Journal of applied crystallography / International Union of Crystallography}, volume = {54}, journal = {Journal of applied crystallography / International Union of Crystallography}, publisher = {Munksgaard}, address = {Copenhagen}, issn = {1600-5767}, doi = {10.1107/S1600576720015344}, pages = {228 -- 236}, year = {2021}, abstract = {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.}, language = {en} } @article{WilhelmiNeumannJaehnertetal.2021, author = {Wilhelmi, Ilka and Neumann, Alexander and J{\"a}hnert, Markus and Ouni, Meriem and Sch{\"u}rmann, Annette}, title = {Enriched alternative splicing in islets of diabetes-susceptible mice}, series = {International journal of molecular sciences}, volume = {22}, journal = {International journal of molecular sciences}, number = {16}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms22168597}, pages = {16}, year = {2021}, abstract = {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.}, language = {en} }