TY - JOUR A1 - Mazurek-Budzyńska, Magdalena A1 - Behl, Marc A1 - Neumann, Richard A1 - Lendlein, Andreas T1 - 4D-actuators by 3D-printing combined with water-based curing JF - Materials today. Communications N2 - 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. KW - 4D-actuation KW - 3D-printing KW - Ink KW - Gripper KW - Fastener Y1 - 2022 U6 - https://doi.org/10.1016/j.mtcomm.2021.102966 SN - 2352-4928 VL - 30 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Chipman, Ariel D. A1 - Ferrier, David E. K. A1 - Brena, Carlo A1 - Qu, Jiaxin A1 - Hughes, Daniel S. T. A1 - Schroeder, Reinhard A1 - Torres-Oliva, Montserrat A1 - Znassi, Nadia A1 - Jiang, Huaiyang A1 - Almeida, Francisca C. A1 - Alonso, Claudio R. A1 - Apostolou, Zivkos A1 - Aqrawi, Peshtewani A1 - Arthur, Wallace A1 - Barna, Jennifer C. J. A1 - Blankenburg, Kerstin P. A1 - Brites, Daniela A1 - Capella-Gutierrez, Salvador A1 - Coyle, Marcus A1 - Dearden, Peter K. A1 - Du Pasquier, Louis A1 - Duncan, Elizabeth J. A1 - Ebert, Dieter A1 - Eibner, Cornelius A1 - Erikson, Galina A1 - Evans, Peter D. A1 - Extavour, Cassandra G. A1 - Francisco, Liezl A1 - Gabaldon, Toni A1 - Gillis, William J. A1 - Goodwin-Horn, Elizabeth A. A1 - Green, Jack E. A1 - Griffiths-Jones, Sam A1 - Grimmelikhuijzen, Cornelis J. P. A1 - Gubbala, Sai A1 - Guigo, Roderic A1 - Han, Yi A1 - Hauser, Frank A1 - Havlak, Paul A1 - Hayden, Luke A1 - Helbing, Sophie A1 - Holder, Michael A1 - Hui, Jerome H. L. A1 - Hunn, Julia P. A1 - Hunnekuhl, Vera S. A1 - Jackson, LaRonda A1 - Javaid, Mehwish A1 - Jhangiani, Shalini N. A1 - Jiggins, Francis M. A1 - Jones, Tamsin E. A1 - Kaiser, Tobias S. A1 - Kalra, Divya A1 - Kenny, Nathan J. A1 - Korchina, Viktoriya A1 - Kovar, Christie L. A1 - Kraus, F. Bernhard A1 - Lapraz, Francois A1 - Lee, Sandra L. A1 - Lv, Jie A1 - Mandapat, Christigale A1 - Manning, Gerard A1 - Mariotti, Marco A1 - Mata, Robert A1 - Mathew, Tittu A1 - Neumann, Tobias A1 - Newsham, Irene A1 - Ngo, Dinh N. A1 - Ninova, Maria A1 - Okwuonu, Geoffrey A1 - Ongeri, Fiona A1 - Palmer, William J. A1 - Patil, Shobha A1 - Patraquim, Pedro A1 - Pham, Christopher A1 - Pu, Ling-Ling A1 - Putman, Nicholas H. A1 - Rabouille, Catherine A1 - Ramos, Olivia Mendivil A1 - Rhodes, Adelaide C. A1 - Robertson, Helen E. A1 - Robertson, Hugh M. A1 - Ronshaugen, Matthew A1 - Rozas, Julio A1 - Saada, Nehad A1 - Sanchez-Gracia, Alejandro A1 - Scherer, Steven E. A1 - Schurko, Andrew M. A1 - Siggens, Kenneth W. A1 - Simmons, DeNard A1 - Stief, Anna A1 - Stolle, Eckart A1 - Telford, Maximilian J. A1 - Tessmar-Raible, Kristin A1 - Thornton, Rebecca A1 - van der Zee, Maurijn A1 - von Haeseler, Arndt A1 - Williams, James M. A1 - Willis, Judith H. A1 - Wu, Yuanqing A1 - Zou, Xiaoyan A1 - Lawson, Daniel A1 - Muzny, Donna M. A1 - Worley, Kim C. A1 - Gibbs, Richard A. A1 - Akam, Michael A1 - Richards, Stephen T1 - The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima JF - PLoS biology N2 - 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. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pbio.1002005 SN - 1545-7885 VL - 12 IS - 11 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Stachanow, Viktoria A1 - Neumann, Uta A1 - Blankenstein, Oliver A1 - Bindellini, Davide A1 - Melin, Johanna A1 - Ross, Richard A1 - Whitaker, Martin J. J. A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Kloft, Charlotte T1 - Exploring dried blood spot cortisol concentrations as an alternative for monitoring pediatric adrenal insufficiency patients BT - a model-based analysis JF - Frontiers in pharmacology N2 - 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. KW - adrenal insufficiency KW - cortisol KW - dried blood spots KW - pediatrics KW - pharmacokinetics KW - binding KW - association KW - red blood cells Y1 - 2022 U6 - https://doi.org/10.3389/fphar.2022.819590 SN - 1663-9812 VL - 13 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Michelet, Robin A1 - Bindellini, Davide A1 - Melin, Johanna A1 - Neumann, Uta A1 - Blankenstein, Oliver A1 - Huisinga, Wilhelm A1 - Johnson, Trevor N. A1 - Whitaker, Martin J. A1 - Ross, Richard A1 - Kloft, Charlotte T1 - Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach JF - Frontiers in Pharmacology N2 - 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. KW - hydrocortisone KW - congenital adrenal hyperplasia KW - population pharmacokinetics KW - middle-out approach KW - pediatrics KW - physiologically-based pharmacokinetics (PBPK) KW - non-linear mixed effects modelling (NLME); KW - maturation Y1 - 2023 U6 - https://doi.org/10.3389/fphar.2022.1090554 SN - 1663-9812 VL - 13 PB - Frontiers Media CY - Lausanne ER -