1,125 research outputs found
Magnetic iron oxide nanoparticles as potential contrast agents for magnetic resonance imaging
This thesis presents the development of novel formulations on the basis of magnetic iron oxide nanoparticles. Optimization of the synthesis route resulted in the development of particles meeting general requirements for eventual applications. Furthermore, the selection of appropriate stabilizing agents imparted the nanoparticles with beneficial features, making an in vivo application possible. In doing so, the formulations seem to be especially promising for the application as contrast agents in magnetic resonance imaging.
Chapter 1 gives a brief insight into current research in the field of magnetic nanoparticles. While the originally promoted idea of dragging nanoparticles to the site of action by a massive external field is becoming less important, the use of magnetic carriers as single and multifunctional imaging agents is gaining in importance.
Chapter 2 describes the synthesis of magnetic iron oxide nanoparticles with optimal properties for MRI contrast enhancement and the comparative assessment of polymeric macromolecules as stabilizers for such nanoparticles. It was revealed that particles covered by poly(ethylene imine)-g-poly(ethylene glycol) performed better than their poly(ethylene imine) counterparts, in terms of stability and cytotoxicity. The systems containing the former polymer showed pronounced colloidal stability even in protein-rich cell media. In addition, cytotoxicity was reduced by more than an order of magnitude. In this respect, the assumptions made in the run-up to the studies have found confirmation. Indeed, the introduction of hydrophilic poly(ethylene glycol) moieties to the polymer backbone positively manipulated the above properties. In addition, the physicochemical properties of the generated iron oxide nanoparticles were found to be excellent, despite the simplicity of the synthesis procedure. The iron oxide cores displayed high crystallinity, high saturation magnetization and superparamagnetic features. The polymer-coated nanoparticles were narrowly distributed around an average diameter of 40 nm and showed relaxation parameters comparable to presently marketed products. Given these results, the established magnetic ferrofluids appear to be interesting for an intracorporal application as an MRI contrast agent.
The assumption that the configuration of magnetic nanoparticles affects cell uptake (mechanisms) and localization, and subsequently cellular MRI signaling, provided a basis for further studies. Chapter 3 includes the evaluation of oppositely charged iron oxide nanoparticle systems with regard to physicochemical properties, cell interaction and cell-constrained relaxometry. The findings of this section confirm that surface potential is the key factor controlling cell internalization of magnetic iron oxide nanoparticles. Particles with a positive zeta potential were taken up to an almost tenfold extent after 24 hours, and with faster kinetics than the negatively charged counterparts. Basically, these results confirm the preliminary assumptions that electrostatic attractive forces between the cell membrane and the nanoparticles favor an enhanced internalization of positive carriers. However, the clear discrepancy in overall uptake led to the conclusion that synergistic effects, such as colloidal stability, also influence the rate of particle accumulation in cells. Both systems were found to be compartmentalized in endosomes after their uptake into cells by a correspondent endocytotic pathway. This cellular confinement caused the relaxation parameters to change in comparison to freely dispersed nanosuspensions, in such a way that the signal contrast in T2-weighted MRI sequences degraded. Nevertheless, phantoms of cells incubated with positively charged nanoparticles still revealed effective signal darkening in these MRI sequences. The results suggest the suspensions examined as promising agents for cell tracking purposes, as here high iron uptake in combination with pronounced relaxivity is required
ââŠdes Volkes, des man niht enahtâŠâ: soziale Randgruppen und AuĂenseiter im Spiegel der österreichischen Chronistik des spĂ€ten Mittelalters unter besonderer BerĂŒcksichtigung der Ăberlieferungen zur Sozialstruktur in KĂ€rnten
1000 Worte Forschung: Laufende Dissertation (Mittelalterliche Geschichte), Alpen-Adria-UniversitÀt Klagenfur
Detection of metastable electronic states by Penning trap mass spectrometry
State-of-the-art optical clocks achieve fractional precisions of
and below using ensembles of atoms in optical lattices or individual ions in
radio-frequency traps. Promising candidates for novel clocks are highly charged
ions (HCIs) and nuclear transitions, which are largely insensitive to external
perturbations and reach wavelengths beyond the optical range, now becoming
accessible to frequency combs. However, insufficiently accurate atomic
structure calculations still hinder the identification of suitable transitions
in HCIs. Here, we report on the discovery of a long-lived metastable electronic
state in a HCI by measuring the mass difference of the ground and the excited
state in Re, the first non-destructive, direct determination of an electronic
excitation energy. This result agrees with our advanced calculations, and we
confirmed them with an Os ion with the same electronic configuration. We used
the high-precision Penning-trap mass spectrometer PENTATRAP, unique in its
synchronous use of five individual traps for simultaneous mass measurements.
The cyclotron frequency ratio of the ion in the ground state to the
metastable state could be determined to a precision of , unprecedented in the heavy atom regime. With a lifetime of about 130
days, the potential soft x-ray frequency reference at has a linewidth of only , and one of the highest electronic quality factor
() ever seen in an experiment. Our low
uncertainty enables searching for more HCI soft x-ray clock transitions, needed
for promising precision studies of fundamental physics in a thus far unexplored
frontier
Observation of a low-lying metastable electronic state in highly charged lead by Penning-trap mass spectrometry
Highly charged ions (HCIs) offer many opportunities for next-generation clock
research due to the vast landscape of available electronic transitions in
different charge states. The development of XUV frequency combs has enabled the
search for clock transitions based on shorter wavelengths in HCIs. However,
without initial knowledge of the energy of the clock states, these narrow
transitions are difficult to be probed by lasers. In this Letter, we provide
experimental observation and theoretical calculation of a long-lived electronic
state in Nb-like Pb which could be used as a clock state. With the mass
spectrometer Pentatrap, the excitation energy of this metastable state is
directly determined as a mass difference at an energy of 31.2(8) eV,
corresponding to one of the most precise relative mass determinations to date
with a fractional uncertainty of . This experimental result
agrees within 1 with two partially different \textit{ab initio}
multi-configuration Dirac-Hartree-Fock calculations of 31.68(13) eV and
31.76(35) eV, respectively. With a calculated lifetime of 26.5(5.3) days, the
transition from this metastable state to the ground state bears a quality
factor of and allows for the construction of a HCI clock
with a fractional frequency instability of
Stromal Expression of Heat-Shock Protein 27 Is Associated with Worse Clinical Outcome in Patients with Colorectal Cancer Lung Metastases
Pulmonary metastases are common in patients with primary colorectal cancer (CRC). Heat-
shock protein 27 (Hsp27) is upregulated in activated fibroblasts during wound healing and
systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs) are also
thought to play a role as prognostic and predictive markers in various malignancies includ-
ing CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. There-
fore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical
implications in patients with CRC lung metastases
Interleukinâ6 initiates muscleâ and adipose tissue wasting in a novel C57BL/6 model of cancerâassociated cachexia
BACKGROUND: Cancerâassociated cachexia (CAC) is a wasting syndrome drastically reducing efficacy of chemotherapy and life expectancy of patients. CAC affects up to 80% of cancer patients, yet the mechanisms underlying the disease are not well understood and no approved diseaseâspecific medication exists. As a multiorgan disorder, CAC can only be studied on an organismal level. To cover the diverse aetiologies of CAC, researchers rely on the availability of a multifaceted pool of cancer models with varying degrees of cachexia symptoms. So far, no tumour model syngeneic to C57BL/6 mice exists that allows direct comparison between cachexigenicâ and nonâcachexigenic tumours. METHODS: MCA207 and CHX207 fibrosarcoma cells were intramuscularly implanted into male or female, 10â11âweekâold C57BL/6J mice. Tumour tissues were subjected to magnetic resonance imaging, immunohistochemicalâ, and transcriptomic analysis. Mice were analysed for tumour growth, body weight and âcomposition, foodâ and water intake, locomotor activity, O(2) consumption, CO(2) production, circulating blood cells, metabolites, and tumourkines. Mice were sacrificed with same tumour weights in all groups. Adipose tissues were examined using highâresolution respirometry, lipolysis measurements in vitro and ex vivo, and radioactive tracer studies in vivo. Gene expression was determined in adiposeâ and muscle tissues by quantitative PCR and Western blotting analyses. Muscles and cultured myotubes were analysed histologically and by immunofluorescence microscopy for myofibre cross sectional area and myofibre diameter, respectively. Interleukinâ6 (Ilâ6) was deleted from cancer cells using CRISPR/Cas9 mediated gene editing. RESULTS: CHX207, but not MCA207âtumourâbearing mice exhibited major clinical features of CAC, including systemic inflammation, increased plasma ILâ6 concentrations (190 pg/mL, P â€Â 0.0001), increased energy expenditure (+28%, P â€Â 0.01), adipose tissue loss (â47%, P â€Â 0.0001), skeletal muscle wasting (â18%, P â€Â 0.001), and body weight reduction (â13%, P â€Â 0.01) 13 days after cancer cell inoculation. Adipose tissue loss resulted from reduced lipid uptake and âsynthesis combined with increased lipolysis but was not associated with elevated betaâadrenergic signalling or adipose tissue browning. Muscle atrophy was evident by reduced myofibre cross sectional area (â21.8%, P â€Â 0.001), increased catabolicâ and reduced anabolic signalling. Deletion of ILâ6 from CHX207 cancer cells completely protected CHX207(IL6KO)âtumourâbearing mice from CAC. CONCLUSIONS: In this study, we present CHX207 fibrosarcoma cells as a novel tool to investigate the mediators and metabolic consequences of CAC in C57BL/6 mice in comparison to nonâcachectic MCA207âtumourâbearing mice. ILâ6 represents an essential trigger for CAC development in CHX207âtumourâbearing mice
High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal, Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications
MiRNAs are discussed as diagnostic and therapeutic molecules. However,
effective miRNA drug treatments with miRNAs are, so far, hampered by the
complexity of the miRNA networks. To identify potential miRNA drugs in
colorectal cancer, we profiled miRNA and mRNA expression in matching normal,
tumor and metastasis tissues of eight patients by Illumina sequencing. We
validated six miRNAs in a large tissue screen containing 16 additional tumor
entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as
constantly de-regulated within the majority of cancers. Of these, we
investigated miRNA-1 as representative in a systems-biology simulation of
cellular cancer models implemented in PyBioS and assessed the effects of
depletion as well as overexpression in terms of miRNA-1 as a potential
treatment option. In this system, miRNA-1 treatment reverted the disease
phenotype with different effectiveness among the patients. Scoring the gene
expression changes obtained through mRNA-Seq from the same patients we show
that the combination of deep sequencing and systems biological modeling can
help to identify patient-specific responses to miRNA treatments. We present
this data as guideline for future pre-clinical assessments of new and
personalized therapeutic options
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