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- ItemPhenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Reichert, Doreen; Friedrichs, Jens; Ritter, Steffi; Käubler, Theresa; Werner, Carsten; Bornhäuser, Martin; Corbeil, DenisXenogenic transplantation models have been developed to study human hematopoiesis in immunocompromised murine recipients. They still have limitations and therefore it is important to delineate all players within the bone marrow that could account for species-specific differences. Here, we evaluated the proliferative capacity, morphological and physical characteristics of human CD34+ hematopoietic stem and progenitor cells (HSPCs) after co-culture on murine or human bone marrow-derived mesenchymal stromal cells (MSCs). After seven days, human CD34+CD133– HSPCs expanded to similar extents on both feeder layers while cellular subsets comprising primitive CD34+CD133+ and CD133+CD34– phenotypes are reduced fivefold on murine MSCs. The number of migrating HSPCs was also reduced on murine cells suggesting that MSC adhesion influences cellular polarization of HSPC. We used atomic force microscopy-based single-cell force spectroscopy to quantify their adhesive interactions. We found threefold higher detachment forces of human HSPCs from murine MSCs compared to human ones. This difference is related to the N-cadherin expression level on murine MSCs since its knockdown abolished their differential adhesion properties with human HSPCs. Our observations highlight phenotypic, morphological and adhesive differences of human HSPCs when cultured on murine or human MSCs, which raise some caution in data interpretation when xenogenic transplantation models are used.
- ItemNon-synchronization of lattice and carrier temperatures in light-emitting diodes([London] : Macmillan Publishers Limited, part of Springer Nature, 2016) Zhang, Jihong; Shih, Tienmo; Lu, Yijun; Merlitz, Holger; Chang, Richard Ru-Gin; Chen, ZhongPulse implementation or switching-off (PISO) of electrical currents has become a common operation in junction-temperature (Tj) measurements for semiconductor devices since 2004. Here we have experimentally discovered a substantial discrepancy between Tj values with and without, PISO (e.g., 36.8 °C versus 76.5 °C above the ambient temperature at 25.0 °C). Our research indicates that methods associated with PISO are flawed due to non-synchronization of lattice temperatures and carrier temperatures in transient states. To scrutinize this discrepancy, we propose a lattice-inertia thermal anchoring mechanism that (1) explains the cause of this discrepancy, (2) helps to develop a remedy to eliminate this discrepancy by identifying three transient phases, (3) has been applied to establishing an original, accurate and noninvasive technique for light-emitting diodes to measure Tj in the absence of PISO. Our finding may pave the foundation for LED communities to further establish reliable junction-temperature measurements based on the identified mechanism.
- ItemDistinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform([London] : Macmillan Publishers Limited, part of Springer Nature, 2016) Müller, Eike; Wang, Weijia; Qiao, Wenlian; Bornhäuser, Martin; Zandstra, Peter W.; Werner, Carsten; Pompe, TiloHomeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.
- ItemMagnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Newland, Ben; Leupelt, Daniel; Zheng, Yu; Thomas, Laurent S.V.; Werner, Carsten; Steinhart, Martin; Wang, WenxinExternally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers and various therapeutics.
- ItemAdam-Gibbs model in the density scaling regime and its implications for the configurational entropy scaling([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Masiewicz, Elżbieta; Grzybowski, Andrzej; Grzybowska, Katarzyna; Pawlus, Sebastian; Pionteck, Jürgen; Paluch, MarianTo solve a long-standing problem of condensed matter physics with determining a proper description of the thermodynamic evolution of the time scale of molecular dynamics near the glass transition, we have extended the well-known Adam-Gibbs model to describe the temperature-volume dependence of structural relaxation times, τα(T, V). We also employ the thermodynamic scaling idea reflected in the density scaling power law, τα = f(T−1V−γ), recently acknowledged as a valid unifying concept in the glass transition physics, to differentiate between physically relevant and irrelevant attempts at formulating the temperature-volume representations of the Adam-Gibbs model. As a consequence, we determine a straightforward relation between the structural relaxation time τα and the configurational entropy SC, giving evidence that also SC(T, V) = g(T−1V−γ) with the exponent γ that enables to scale τα(T, V). This important findings have meaningful implications for the connection between thermodynamics and molecular dynamics near the glass transition, because it implies that τα can be scaled with SC.
- ItemMaximal rectification ratios for idealized bi-segment thermal rectifiers([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Shih, Tien-Mo; Gao, Zhaojing; Guo, Ziquan; Merlitz, Holger; Pagni, Patrick J.; Chen, ZhongThermal rectifiers whose forward heat fluxes are greater than reverse counterparts have been extensively studied. Here we have discovered, idealized and derived the ultimate limit of such rectification ratios, which are partially validated by numerical simulations, experiments and micro-scale Hamiltonian-oscillator analyses. For rectifiers whose thermal conductivities (κ) are linear with the temperature, this limit is simply a numerical value of 3. For those whose conductivities are nonlinear with temperatures, the maxima equal κmax/κmin, where two extremes denote values of the solid segment materials that can be possibly found or fabricated within a reasonable temperature range. Recommendations for manufacturing high-ratio rectifiers are also given with examples. Under idealized assumptions, these proposed rectification limits cannot be defied by any bi-segment thermal rectifiers.
- ItemAn NMR Study of Biomimetic Fluorapatite - Gelatine Mesocrystals([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Vyalikh, Anastasia; Simon, Paul; Rosseeva, Elena; Buder, Jana; Scheler, Ulrich; Kniep, RüdigerThe mesocrystal system fluoroapatite—gelatine grown by double-diffusion is characterized by hierarchical composite structure on a mesoscale. In the present work we apply solid state NMR to characterize its structure on the molecular level and provide a link between the structural organisation on the mesoscale and atomistic computer simulations. Thus, we find that the individual nanocrystals are composed of crystalline fluorapatite domains covered by a thin boundary apatite-like layer. The latter is in contact with an amorphous layer, which fills the interparticle space. The amorphous layer is comprised of the organic matrix impregnated by isolated phosphate groups, Ca3F motifs and water molecules. Our NMR data provide clear evidence for the existence of precursor complexes in the gelatine phase, which were not involved in the formation of apatite crystals, proving hence theoretical predictions on the structural pre-treatment of gelatine by ion impregnation. The interfacial interactions, which may be described as the glue holding the composite materials together, comprise hydrogen bond interactions with the apatite PO43− groups. The reported results are in a good agreement with molecular dynamics simulations, which address the mechanisms of a growth control by collagen fibers and with experimental observations of an amorphous cover layer in biominerals.