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With its need for high SNR and short acquisition times, Cardiac MRI (CMR) is an intriguing target application for ultrahigh field MRI. Due to the sheer size of the upper torso, however, the known RF issues of 7T MRI are also most prominent in CMR. Recent years brought substantial progress but the full potential of the ultrahigh field for CMR is yet to be exploited. Parallel transmission (pTx) is a promising approach in this context and several groups have already reported B1 shimming for 7T CMR. In such a static pTx application amplitudes and phases of all Tx channels are adjusted individually but otherwise imaging techniques established in current clinical practice 1.5 T and 3 T are applied. More advanced forms of pTx as spatially selective excitation (SSE) using Transmit SENSE promise additional benefits like faster imaging with reduced fields of view or improved SAR control. SSE requires the full dynamic capabilities of pTx, however, and for the majority of today's implemented pTx hardware the internal synchronization of the Tx array does not easily permit external triggering as needed for CMR. Here we report a software solution to this problem and demonstrate the feasibility of CINE CMR at 7 T using a Tx array.
Vollzug der Schenkung einer Unterbeteiligung : BGH, Urteil vom 29.11.2011 - II ZR 306/09 : Anmerkung
(2012)
Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
The radio-based wireless data communication has made the realization of new technical solutions possible in many fields of the automation technology (AT). For about ten years, a constant disproportionate growth of wireless technologies can be observed in the automation technology.
However, it shows that especially for the AT, conventional technologies of office automation are unsuitable and/or not manageable. The employment of mobile services in the industrial automation technology has the potential of significant cost and time savings. This leads to an increased productivity in various fields of the AT, for example in the factory and process automation or in production logistics. In this paper technologies and solutions for an automation-suited supply of mobile wireless services will be introduced under the criteria of real time suitability, IT-security and service orientation.
Emphasis will be put on the investigation and development of wireless convergence layers for different radio technologies, on the central provision of support services for an easy-to-use, central, backup enabled management of combined wired / wireless networks and on the study on integrability in a Profinet real-time Ethernet network.
Für die Ermittlung der erforderlichen Einspanntiefe von eingespannten Stahlquerschnitten in Betonkonstruktionen existieren verschiedene Bemessungsmodelle. Diese basieren vorwiegend auf Grundlage nationaler Normen wie z. B. DIN 18800 [1] und DIN 1045 [2], die durch die europäische Normung ersetzt wurden. Aus diesem Grund wird in diesem Aufsatz ein Berechnungsmodell für die erforderliche Einspanntiefe von eingespannten Stahlquerschnitten in Betonkonstruktionen auf Grundlage des Eurocodes vorgestellt. Das Grundgerüst für dieses Berechnungsmodell bildet das Verfahren nach Kindmann und Laumann, welches in [3] behandelt wurde. Gleichzeitig werden neue Formeln zur direkten Ermittlung der Mindesteinspanntiefe vorgestellt. Behandelt werden gewalzte I-Profile für einachsige Biegung um die starke Achse (y-y) mit Drucknormalkraft.
All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.