@article{MazurekBudzyńskaBehlNeumannetal.2022, author = {Mazurek-Budzyńska, Magdalena and Behl, Marc and Neumann, Richard and Lendlein, Andreas}, title = {4D-actuators by 3D-printing combined with water-based curing}, series = {Materials today. Communications}, volume = {30}, journal = {Materials today. Communications}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2352-4928}, doi = {10.1016/j.mtcomm.2021.102966}, pages = {7}, year = {2022}, abstract = {The shape and the actuation capability of state of the art robotic devices typically relies on multimaterial systems from a combination of geometry determining materials and actuation components. Here, we present multifunctional 4D-actuators processable by 3D-printing, in which the actuator functionality is integrated into the shaped body. The materials are based on crosslinked poly(carbonate-urea-urethane) networks (PCUU), synthesized in an integrated process, applying reactive extrusion and subsequent water-based curing. Actuation capability could be added to the PCUU, prepared from aliphatic oligocarbonate diol, isophorone diisocyanate (IPDI) and water, in a thermomechanical programming process. When programmed with a strain of epsilon(prog) = 1400\% the PCUU networks exhibited actuation apparent by reversible elongation epsilon'(rev) of up to 22\%. In a gripper a reversible bending epsilon'(rev)((be)(nd)()) in the range of 37-60\% was achieved when the actuation temperature (T-high) was varied between 45 degrees C and 49 degrees C. The integration of actuation and shape formation could be impressively demonstrated in two PCUU-based reversible fastening systems, which were able to hold weights of up to 1.1 kg. In this way, the multifunctional materials are interesting candidate materials for robotic applications where a freedom in shape design and actuation is required as well as for sustainable fastening systems.}, language = {en} } @article{ChipmanFerrierBrenaetal.2014, author = {Chipman, Ariel D. and Ferrier, David E. K. and Brena, Carlo and Qu, Jiaxin and Hughes, Daniel S. T. and Schroeder, Reinhard and Torres-Oliva, Montserrat and Znassi, Nadia and Jiang, Huaiyang and Almeida, Francisca C. and Alonso, Claudio R. and Apostolou, Zivkos and Aqrawi, Peshtewani and Arthur, Wallace and Barna, Jennifer C. J. and Blankenburg, Kerstin P. and Brites, Daniela and Capella-Gutierrez, Salvador and Coyle, Marcus and Dearden, Peter K. and Du Pasquier, Louis and Duncan, Elizabeth J. and Ebert, Dieter and Eibner, Cornelius and Erikson, Galina and Evans, Peter D. and Extavour, Cassandra G. and Francisco, Liezl and Gabaldon, Toni and Gillis, William J. and Goodwin-Horn, Elizabeth A. and Green, Jack E. and Griffiths-Jones, Sam and Grimmelikhuijzen, Cornelis J. P. and Gubbala, Sai and Guigo, Roderic and Han, Yi and Hauser, Frank and Havlak, Paul and Hayden, Luke and Helbing, Sophie and Holder, Michael and Hui, Jerome H. L. and Hunn, Julia P. and Hunnekuhl, Vera S. and Jackson, LaRonda and Javaid, Mehwish and Jhangiani, Shalini N. and Jiggins, Francis M. and Jones, Tamsin E. and Kaiser, Tobias S. and Kalra, Divya and Kenny, Nathan J. and Korchina, Viktoriya and Kovar, Christie L. and Kraus, F. Bernhard and Lapraz, Francois and Lee, Sandra L. and Lv, Jie and Mandapat, Christigale and Manning, Gerard and Mariotti, Marco and Mata, Robert and Mathew, Tittu and Neumann, Tobias and Newsham, Irene and Ngo, Dinh N. and Ninova, Maria and Okwuonu, Geoffrey and Ongeri, Fiona and Palmer, William J. and Patil, Shobha and Patraquim, Pedro and Pham, Christopher and Pu, Ling-Ling and Putman, Nicholas H. and Rabouille, Catherine and Ramos, Olivia Mendivil and Rhodes, Adelaide C. and Robertson, Helen E. and Robertson, Hugh M. and Ronshaugen, Matthew and Rozas, Julio and Saada, Nehad and Sanchez-Gracia, Alejandro and Scherer, Steven E. and Schurko, Andrew M. and Siggens, Kenneth W. and Simmons, DeNard and Stief, Anna and Stolle, Eckart and Telford, Maximilian J. and Tessmar-Raible, Kristin and Thornton, Rebecca and van der Zee, Maurijn and von Haeseler, Arndt and Williams, James M. and Willis, Judith H. and Wu, Yuanqing and Zou, Xiaoyan and Lawson, Daniel and Muzny, Donna M. and Worley, Kim C. and Gibbs, Richard A. and Akam, Michael and Richards, Stephen}, title = {The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima}, series = {PLoS biology}, volume = {12}, journal = {PLoS biology}, number = {11}, publisher = {PLoS}, address = {San Fransisco}, issn = {1545-7885}, doi = {10.1371/journal.pbio.1002005}, pages = {24}, year = {2014}, abstract = {Myriapods (e. g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.}, language = {en} } @article{StachanowNeumannBlankensteinetal.2022, author = {Stachanow, Viktoria and Neumann, Uta and Blankenstein, Oliver and Bindellini, Davide and Melin, Johanna and Ross, Richard and Whitaker, Martin J. J. and Huisinga, Wilhelm and Michelet, Robin and Kloft, Charlotte}, title = {Exploring dried blood spot cortisol concentrations as an alternative for monitoring pediatric adrenal insufficiency patients}, series = {Frontiers in pharmacology}, volume = {13}, journal = {Frontiers in pharmacology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1663-9812}, doi = {10.3389/fphar.2022.819590}, pages = {8}, year = {2022}, abstract = {Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling. Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations. In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions. In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.}, language = {en} } @article{MicheletBindelliniMelinetal.2023, author = {Michelet, Robin and Bindellini, Davide and Melin, Johanna and Neumann, Uta and Blankenstein, Oliver and Huisinga, Wilhelm and Johnson, Trevor N. and Whitaker, Martin J. and Ross, Richard and Kloft, Charlotte}, title = {Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach}, series = {Frontiers in Pharmacology}, volume = {13}, journal = {Frontiers in Pharmacology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1663-9812}, doi = {10.3389/fphar.2022.1090554}, pages = {14}, year = {2023}, abstract = {Introduction: Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level. Methods: Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature. Results: Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBG(NLME) stable around 0.5 mu M vs. steady increase from 0.35 to 0.8 mu M for CBG (PBPK)). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (\& UDelta;OFV > -15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias. Discussion: Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK.}, language = {en} }