25 results
Search Results
Now showing 1 - 10 of 25
- ItemZebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells(London : Nature Publishing Group, 2017) Arulmozhivarman, Guruchandar; Kräter, Martin; Wobus, Manja; Friedrichs, Jens; Bejestani, Elham Pishali; Müller, Katrin; Lambert, Katrin; Alexopoulou, Dimitra; Dahl, Andreas; Stöter, Martin; Bickle, Marc; Shayegi, Nona; Hampe, Jochen; Stölzel, Friedrich; Brand, Michael; von Bonin, Malte; Bornhäuser, MartinThe identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice. Interestingly, VPA increased CD34+ cell adhesion to primary mesenchymal stromal cells and reduced their in vitro chemokine-mediated migration capacity. In line with this, VPA-treated human CD34+ cells showed reduced homing and early engraftment in a xenograft transplant model, but retained their long-term engraftment potential in vivo, and maintained their differentiation ability both in vitro and in vivo. In summary, our data demonstrate that certain HDACIs lead to a net expansion of hHSPCs with retained long-term engraftment potential and could be further explored as candidate compounds to amplify ex-vivo engineered peripheral blood stem cells.
- ItemDirect estimation of the global distribution of vertical velocity within cirrus clouds(London : Nature Publishing Group, 2017) Barahona, Donifan; Molod, Andrea; Kalesse, HeikeCirrus clouds determine the radiative balance of the upper troposphere and the transport of water vapor across the tropopause. The representation of vertical wind velocity, W, in atmospheric models constitutes the largest source of uncertainty in the calculation of the cirrus formation rate. Using global atmospheric simulations with a spatial resolution of 7 km we obtain for the first time a direct estimate of the distribution of W at the scale relevant for cirrus formation, validated against long-term observations at two different ground sites. The standard deviation in W, σ w, varies widely over the globe with the highest values resulting from orographic uplift and convection, and the lowest occurring in the Arctic. Globally about 90% of the simulated σ w values are below 0.1 m s-1 and about one in 104 cloud formation events occur in environments with σ w > 0.8 m s-1. Combining our estimate with reanalysis products and an advanced cloud formation scheme results in lower homogeneous ice nucleation frequency than previously reported, and a decreasing average ice crystal concentration with decreasing temperature. These features are in agreement with observations and suggest that the correct parameterization of σ w is critical to simulate realistic cirrus properties.
- ItemCorrelated electronic decay in expanding clusters triggered by intense XUV pulses from a Free-Electron-Laser(London : Nature Publishing Group, 2017) Oelze, Tim; Schütte, Bernd; Müller, Maria; Müller, Jan P.; Wieland, Marek; Frühling, Ulrike; Drescher, Markus; Al-Shemmary, Alaa; Golz, Torsten; Stojanovic, Nikola; Krikunova, MariaIrradiation of nanoscale clusters and large molecules with intense laser pulses transforms them into highly-excited non- equilibrium states. The dynamics of intense laser-cluster interaction is encoded in electron kinetic energy spectra, which contain signatures of direct photoelectron emission as well as emission of thermalized nanoplasma electrons. In this work we report on a so far not observed spectrally narrow bound state signature in the electron kinetic energy spectra from mixed Xe core - Ar shell clusters ionized by intense extreme-ultraviolet (XUV) pulses from a free-electron-laser. This signature is attributed to the correlated electronic decay (CED) process, in which an excited atom relaxes and the excess energy is used to ionize the same or another excited atom or a nanoplasma electron. By applying the terahertz field streaking principle we demonstrate that CED-electrons are emitted at least a few picoseconds after the ionizing XUV pulse has ended. Following the recent finding of CED in clusters ionized by intense near-infrared laser pulses, our observation of CED in the XUV range suggests that this process is of general relevance for the relaxation dynamics in laser produced nanoplasmas.
- ItemImpact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells(London : Nature Publishing Group, 2018) Brownlee, William J.; Seib, F. PhilippBreast cancer cells adapt to the hypoxic tumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cell phenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocytic uptake and specific intracellular trafficking. The aim of this study was to examine the impact of hypoxia and simulated reperfusion on the in vitro uptake and release of nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal changes in the hypoxic circuit (e.g. HIF-1α expression). The preconditioned cells were then dosed with nanoparticles for 45 or 180 minutes emulating nanomedicine access following tumor reperfusion. Hypoxic preconditioning significantly increased nanoparticle retention by up to 10% when compared to normoxic cultures, with the greatest relative difference between normoxic and hypoxic cultures occurring with a 45 minute dosing interval. Exocytosis studies indicated that the preconditioned cells had a significantly increased nanoparticle efflux (up to 9%) when compared to normoxic cells. Overall, we were able to show that hypoxic preconditioning regulates both the endocytosis and exocytosis of nanomedicines in human breast cancer cells.
- ItemSwitchable plasmonic routers controlled by external magnetic fields by using magneto-plasmonic waveguides(London : Nature Publishing Group, 2018) Ho, Kum-Song; Im, Song-Jin; Pae, Ji-Song; Ri, Chol-Song; Han, Yong-Ha; Herrmann, JoachimWe analytically and numerically investigate magneto-plasmons in metal films surrounded by a ferromagnetic dielectric. In such waveguide using a metal film with a thickness exceeding the Skin depth, an external magnetic field in the transverse direction can induce a significant spatial asymmetry of mode distribution. Superposition of the odd and the even asymmetric modes over a distance leads to a concentration of the energy on one interface which is switched to the other interface by the magnetic field reversal. The requested magnitude of magnetization is exponentially reduced with the increase of the metal film thickness. Based on this phenomenon, we propose a waveguide-integrated magnetically controlled switchable plasmonic routers with 99-%-high contrast within the optical bandwidth of tens of THz. This configuration can also operate as a magneto-plasmonic modulator.
- ItemNovel insights on new particle formation derived from a pan-european observing system(London : Nature Publishing Group, 2018) Dall’Osto, M.; Beddows, D.C.S.; Asmi, A.; Poulain, L.; Hao, L.; Freney, E.; Allan, J.D.; Canagaratna, M.; Crippa, M.; Bianchi, F.; de Leeuw, G.; Eriksson, A.; Swietlicki, E.; Hansson, H.C.; Henzing, J.S.; Granier, C.; Zemankova, K.; Laj, P.; Onasch, T.; Prevot, A.; Putaud, J. P.; Sellegri, K.; Vidal, M.; Virtanen, A.; Simo, R.; Worsnop, D.; O’Dowd, C.; Kulmala, M.; Harrison, Roy M.The formation of new atmospheric particles involves an initial step forming stable clusters less than a nanometre in size (<~1 nm), followed by growth into quasi-stable aerosol particles a few nanometres (~1-10 nm) and larger (>~10 nm). Although at times, the same species can be responsible for both processes, it is thought that more generally each step comprises differing chemical contributors. Here, we present a novel analysis of measurements from a unique multi-station ground-based observing system which reveals new insights into continental-scale patterns associated with new particle formation. Statistical cluster analysis of this unique 2-year multi-station dataset comprising size distribution and chemical composition reveals that across Europe, there are different major seasonal trends depending on geographical location, concomitant with diversity in nucleating species while it seems that the growth phase is dominated by organic aerosol formation. The diversity and seasonality of these events requires an advanced observing system to elucidate the key processes and species driving particle formation, along with detecting continental scale changes in aerosol formation into the future.
- ItemCationic double K-hole pre-edge states of CS2 and SF6(London : Nature Publishing Group, 2017) Feifel, R.; Eland, J.H.D.; Carniato, S.; Selles, P.; Püttner, R.; Koulentianos, D.; Marchenko, T.; Journel, L.; Guillemin, R.; Goldsztejn, G.; Travnikova, O.; Ismail, I.; Miranda, B. Cunha de; Lago, A.F.; Céolin, D.; Lablanquie, P.; Penent, F.; Piancastelli, M.N.; Simon, M.Recent advances in X-ray instrumentation have made it possible to measure the spectra of an essentially unexplored class of electronic states associated with double inner-shell vacancies. Using the technique of single electron spectroscopy, spectra of states in CS2 and SF6 with a double hole in the K-shell and one electron exited to a normally unoccupied orbital have been obtained. The spectra are interpreted with the aid of a high-level theoretical model giving excellent agreement with the experiment. The results shed new light on the important distinction between direct and conjugate shake-up in a molecular context. In particular, systematic similarities and differences between pre-edge states near single core holes investigated in X-ray absorption spectra and the corresponding states near double core holes studied here are brought out.
- ItemLimbal stromal cells derived from porcine tissue demonstrate mesenchymal characteristics in vitro(London : Nature Publishing Group, 2017) Fernández-Pérez, Julia; Binner, Marcus; Werner, Carsten; Bray, Laura J.Limbal stromal cells (LSCs) from the human ocular surface display mesenchymal stromal cell characteristics in vitro. In this study, we isolated cells from the porcine limbal stroma (pLSCs), characterised them, and evaluated their ability to support angiogenesis and the culture of porcine limbal epithelial stem cells (pLESCs). The isolated cells adhered to plastic and grew in monolayers in vitro using serum-supplemented or serum-free medium. The pLSCs demonstrated expression of CD29, and cross-reactivity with anti-human CD45, CD90, CD105, CD146, and HLA-ABC. However, expression of CD105, CD146 and HLA-ABC reduced when cultured in serum-free medium. PLSCs did not undergo adipogenic or osteogenic differentiation, but differentiated towards the chondrogenic lineage. Isolated cells were also co-cultured with human umbilical vein endothelial cells (HUVECs) in star-shaped Poly(ethylene glycol) (starPEG)-heparin hydrogels to assess their pericyte capacity which supported angiogenesis networks of HUVECs. PLSCs supported the three dimensional HUVEC network for 7 days. The isolated cells were further growth-arrested and evaluated as feeder cells for pLESC expansion on silk fibroin membranes, as a potential carrier material for transplantation. PLSCs supported the growth of pLESCs comparably to murine 3T3 cells. In conclusion, although pLSCs were not completely comparable to their human counterpart, they display several mesenchymal-like characteristics in vitro.
- ItemAdvanced-Retarded Differential Equations in Quantum Photonic Systems(London : Nature Publishing Group, 2017) Alvarez-Rodriguez, Unai; Perez-Leija, Armando; Egusquiza, Iñigo L.; Gräfe, Markus; Sanz, Mikel; Lamata, Lucas; Szameit, Alexander; Solano, EnriqueWe propose the realization of photonic circuits whose dynamics is governed by advanced-retarded differential equations. Beyond their mathematical interest, these photonic configurations enable the implementation of quantum feedback and feedforward without requiring any intermediate measurement. We show how this protocol can be applied to implement interesting delay effects in the quantum regime, as well as in the classical limit. Our results elucidate the potential of the protocol as a promising route towards integrated quantum control systems on a chip.
- ItemDetection of small bunches of ions using image charges(London : Nature Publishing Group, 2018) Räcke, Paul; Spemann, Daniel; Gerlach, Jürgen W.; Rauschenbach, Bernd; Meijer, JanA concept for detection of charged particles in a single fly-by, e.g. within an ion optical system for deterministic implantation, is presented. It is based on recording the image charge signal of ions moving through a detector, comprising a set of cylindrical electrodes. This work describes theoretical and practical aspects of image charge detection (ICD) and detector design and its application in the context of real time ion detection. It is shown how false positive detections are excluded reliably, although the signal-to-noise ratio is far too low for time-domain analysis. This is achieved by applying a signal threshold detection scheme in the frequency domain, which - complemented by the development of specialised low-noise preamplifier electronics - will be the key to developing single ion image charge detection for deterministic implantation.
- «
- 1 (current)
- 2
- 3
- »