Synthesis and Characterization of Iron Oxide Nanoparticles and Investigation of their Biocompatibility on Astrocyte Cultures

Magnetic iron oxide nanoparticles (IONPs) are used as tools for a wide range of biomedical and (neuro)biological applications, for example as contrast agent in magnetic resonance imaging, as transporter for drug delivery across biological barriers or for cancer treatment by magnetic field-induced hyperthermia. However, the knowledge on the effects of such particles on brain cells have only recently been addressed. This thesis describes the synthesis and characterization of citrate- and dimercaptosuccinate (DMSA)-coated IONPs. In addition, the uptake, reactivity and biocompatibility of such particles were investigated for astrocyte-rich primary cultures as a model system for brain astrocytes. Citrate- and DMSA-coated IONPs were accumulated by viable cultured astrocytes in a time- and concentration-dependent process leading to more than 100fold elevated specific cellular iron contents. Electron microscopy revealed that IONPs were present in intracellular vesicles as well as attached extracellularly to the cell membrane. Lowering the incubation temperature to 4°C reduced the iron accumulation to about 50% which represented almost exclusively membrane associated extracellular IONPs. Presence of an external magnetic field increased the amount of cellular iron by 2-4fold, while presence of serum strongly reduced IONP-accumulation by up to 90% compared with the respective controls. Application of endocytosis inhibitors revealed that clathrin-mediated endocytosis and macropinocytosis contributed to IONP-uptake in serum-containing conditions. However, additional mechanisms are responsible for IONP-uptake under serum-free conditions. Prolonged presence of IONPs in cultured astrocytes for up to 7 d after a transient loading period of 4 h neither compromised cell viability nor affected basic metabolic pathways. However, a transient formation of reactive oxygen species and a delayed upregulation of cellular ferritin indicate that iron ions were liberated from the accumulated particles. In summary, this thesis revealed that viable astrocytes efficiently take up and safely store IONPs and IONP-derived iron, supporting the view that such particles can be used as save tools for diagnostic or therapeutic approaches in the brain

Nuclear Charge Radius of 12^{12}Be

The nuclear charge radius of $^{12}$Be was precisely determined using the technique of collinear laser spectroscopy on the $2s_{1/2}\rightarrow 2p_{1/2, 3/2}$ transition in the Be$^{+}$ ion. The mean square charge radius increases from $^{10}$Be to $^{12}$Be by \delta ^{10,12} = 0.69(5) \fm^{2} compared to \delta ^{10,11} = 0.49(5) \fm^{2} for the one-neutron halo isotope $^{11}$Be. Calculations in the fermionic molecular dynamics approach show a strong sensitivity of the charge radius to the structure of $^{12}$Be. The experimental charge radius is consistent with a breakdown of the N=8 shell closure.Comment: 5 pages, 3 figure

Collinear laser spectroscopy of atomic cadmium

Hyperfine structure $A$ and $B$ factors of the atomic 5s\,5p\,\; ^3\rm{P}_2 \rightarrow 5s\,6s\,\; ^3\rm{S}_1 transition are determined from collinear laser spectroscopy data of $^{107-123}$Cd and $^{111m-123m}$Cd. Nuclear magnetic moments and electric quadrupole moments are extracted using reference dipole moments and calculated electric field gradients, respectively. The hyperfine structure anomaly for isotopes with $s_{1/2}$ and $d_{5/2}$ nuclear ground states and isomeric $h_{11/2}$ states is evaluated and a linear relationship is observed for all nuclear states except $s_{1/2}$. This corresponds to the Moskowitz-Lombardi rule that was established in the mercury region of the nuclear chart but in the case of cadmium the slope is distinctively smaller than for mercury. In total four atomic and ionic levels were analyzed and all of them exhibit a similar behaviour. The electric field gradient for the atomic 5s\,5p\,\; ^3\mathrm{P}_2 level is derived from multi-configuration Dirac-Hartree-Fock calculations in order to evaluate the spectroscopic nuclear quadrupole moments. The results are consistent with those obtained in an ionic transition and based on a similar calculation.Comment: 12 pages, 5 figure

Warm Cores around Regions of Low-Mass Star Formation

Warm cores (or hot corinos) around low-mass protostellar objects show a rich chemistry with strong spatial variations. This chemistry is generally attributed to the sublimation of icy mantles on dust grains initiated by the warming effect of the stellar radiation. We have used a model of the chemistry in warm cores in which the sublimation process is based on extensive laboratory data; these data indicate that sublimation from mixed ices occurs in several well-defined temperature bands. We have determined the position of these bands for the slow warming by a solar-mass star. The resulting chemistry is dominated by the sublimation process and by subsequent gas-phase reactions; strong spatial and temporal variations in certain molecular species are found to occur, and our results are, in general, consistent with observational results for the well-studied source IRAS 16293-2422. The model used is similar to one that describes the chemistry of hot cores. We infer that the chemistry of both hot cores and warm cores may be described by the same model (suitably adjusted for different physical parameters).Comment: 11 pages, 5 figures, 2 tables. Accepted by MNRA

Precision Test of Many-Body QED in the Be+^+ 2p2p Fine Structure Doublet Using Short-Lived Isotopes

Absolute transition frequencies of the 2s\; ^2{\rm S}_{1/2} \rightarrow 2p\;^2\mathrm{P}_{1/2,3/2} transitions in Be$^+$ were measured for the isotopes $^{7,9-12}$Be. The fine structure splitting of the $2p$ state and its isotope dependence are extracted and compared to results of \textit{ab initio} calculations using explicitly correlated basis functions, including relativistic and quantum electrodynamics effects at the order of $m \alpha^6$ and $m \alpha^7 \ln \alpha$. Accuracy has been improved in both the theory and experiment by 2 orders of magnitude, and good agreement is observed. This represents one of the most accurate tests of quantum electrodynamics for many-electron systems, being insensitive to nuclear uncertainties.Comment: 5 pages, 2 figure

Clinical case-study describing the use of skin-perichondrium-cartilage graft from the auricular concha to cover large defects of the nose

<p>Abstract</p> <p>Background</p> <p>The composite graft from the conchal cartilage is a graft that is often used, especially in surgery on the nose, due to its capacity to resolve problems of cover and tissue deficit, arising from the removal of neoplasms or as the result of trauma, burns or following over-aggressive rhinoplasty. We have started to use skin-perichondrium-cartilage graft from the ear to cover large areas of the nose with very satisfying results as well as we describe in the reported clinical case.</p> <p>Methods</p> <p>The operation consisted of reconstruction of the cartilaginous nasal septum, which had previously been removed, using two vestibular labial mucosa flaps to reconstruct the mucosa, and cartilage from the ear conch for the cartilaginous septum. After this, the skin edges of the fistula were turned to recreate the inner lining of the nose and form a vascular base of wide area to accept the composite graft. The case concerns a female 74-year old patient who had undergone several oncological surgery for a relapsing basal cell carcinoma on the dorsum of the nose. The operation consisted of reconstruction of the cartilaginous nasal septum using two vestibular labial mucosa flaps to reconstruct the mucosa, and cartilage from the ear conch for the cartilaginous septum.</p> <p>Results</p> <p>The perichondrial cutaneous graft has shown in this surgical case very favorable peculiarities that make it usable even in facial plastic surgery.</p> <p>Conclusions</p> <p>We believe that the positive experience that we achieved in the use of composite grafts for the reconstruction of large areas of the nose could be interesting for others surgeons.</p

Synthese und Charakterisierung von Eisenoxid-Nanopartikeln und Untersuchung ihrer Biokompatibilität an Astrozytenkulturen

Magnetic iron oxide nanoparticles (IONPs) are used as tools for a wide range of biomedical and (neuro)biological applications, for example as contrast agent in magnetic resonance imaging, as transporter for drug delivery across biological barriers or for cancer treatment by magnetic field-induced hyperthermia. However, the knowledge on the effects of such particles on brain cells have only recently been addressed. This thesis describes the synthesis and characterization of citrate- and dimercaptosuccinate (DMSA)-coated IONPs. In addition, the uptake, reactivity and biocompatibility of such particles were investigated for astrocyte-rich primary cultures as a model system for brain astrocytes. Citrate- and DMSA-coated IONPs were accumulated by viable cultured astrocytes in a time- and concentration-dependent process leading to more than 100fold elevated specific cellular iron contents. Electron microscopy revealed that IONPs were present in intracellular vesicles as well as attached extracellularly to the cell membrane. Lowering the incubation temperature to 4°C reduced the iron accumulation to about 50% which represented almost exclusively membrane associated extracellular IONPs. Presence of an external magnetic field increased the amount of cellular iron by 2-4fold, while presence of serum strongly reduced IONP-accumulation by up to 90% compared with the respective controls. Application of endocytosis inhibitors revealed that clathrin-mediated endocytosis and macropinocytosis contributed to IONP-uptake in serum-containing conditions. However, additional mechanisms are responsible for IONP-uptake under serum-free conditions. Prolonged presence of IONPs in cultured astrocytes for up to 7 d after a transient loading period of 4 h neither compromised cell viability nor affected basic metabolic pathways. However, a transient formation of reactive oxygen species and a delayed upregulation of cellular ferritin indicate that iron ions were liberated from the accumulated particles. In summary, this thesis revealed that viable astrocytes efficiently take up and safely store IONPs and IONP-derived iron, supporting the view that such particles can be used as save tools for diagnostic or therapeutic approaches in the brain