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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.
Design, evaluation and comparison of endorectal coils for hybrid MR-PET imaging of the prostate
(2020)
Prostate cancer is one of the most common cancers among men and its early detection is critical for its successful treatment. The use of multimodal imaging, such as MR-PET, is most advantageous as it is able to provide detailed information about the prostate. However, as the human prostate is flexible and can move into different positions under external conditions, it is important to localise the focused region-of-interest using both MRI and PET under identical circumstances. In this work, we designed five commonly used linear and quadrature radiofrequency surface coils suitable for hybrid MR-PET use in endorectal applications. Due to the endorectal design and the shielded PET insert, the outer face of the coils investigated was curved and the region to be imaged was outside the volume of the coil. The tilting angles of the coils were varied with respect to the main magnetic field direction. This was done to approximate the various positions from which the prostate could be imaged. The transmit efficiencies and safety excitation efficiencies from simulations, together with the signal-to-noise ratios from the MR images were calculated and analysed. Overall, it was found that the overlapped loops driven in quadrature were superior to the other types of coils we tested. In order to determine the effect of the different coil designs on PET, transmission scans were carried out, and it was observed that the differences between attenuation maps with and without the coils were negligible. The findings of this work can provide useful guidance for the integration of such coil designs into MR-PET hybrid systems in the future.
Within the Crystal Clear Collaboration four centres are developing 2nd generation high performance small animal PET scanners for different kinds of animals and medical applications. The first prototypes are PMT-based systems including depth of interaction (DOI) detection by using a phoswich layer of LSO and LuYAP. The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in FOVs caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN) was used. The simulations have shown that all PMT designs with one-to-one coupling of crystals have a very nonlinear axial sensitivity profile. By shifting every other PMT 1/4 of a PMT length in axial direction the sampling of the FOVs became more homogeneous. At an energy threshold of 350keV the regression coefficient increases from 0.818 for the non-shifted to 0.993 for the shifted design. Simulations of a point source centred in the FOV (threshold: 350keV) resulted in sensitivities of 4.2% for a 4×20PMT (LSO/LuYAP a 10mm) and 3.8% for a 4×16PMT (LSO/LuYAP a 8mm) ring design. The 3D-MLEM reconstruction of a point source shows the enormous improvement of resolution using a crystal double layer with DOI (3.1mm at 40mm from CFOV) instead of a 20mm single layer (11.9mm).
Within the Crystal Clear Collaboration (CCC), four centers are developing second generation high performance small animal positron emission tomography (PET) scanners for different kinds of animals and medical applications. The first prototypes are photomultiplier tube (PMT)-based systems including depth of interaction (DOI) detection by using a phoswich layer of lutetium oxyorthosilicate (LSO) and lutetium yttrium aluminum perovskite (LuYAP). The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in fields of view (FOVs) caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN, Geneva, Switzerland) was used.
Design of enzyme reactors as chromatographic columns for racemic resolution of amino acid esters
(1989)
The maintenance of wind turbines is of growing importance considering the transition to renewable energy. This paper presents a multi-robot-approach for automated wind turbine maintenance including a novel climbing robot. Currently, wind turbine maintenance remains a manual task, which is monotonous, dangerous, and also physically demanding due to the large scale of wind turbines. Technical climbers are required to work at significant heights, even in bad weather conditions. Furthermore, a skilled labor force with sufficient knowledge in repairing fiber composite material is rare. Autonomous mobile systems enable the digitization of the maintenance process. They can be designed for weather-independent operations. This work contributes to the development and experimental validation of a maintenance system consisting of multiple robotic platforms for a variety of tasks, such as wind turbine tower and rotor blade service. In this work, multicopters with vision and LiDAR sensors for global inspection are used to guide slower climbing robots. Light-weight magnetic climbers with surface contact were used to analyze structure parts with non-destructive inspection methods and to locally repair smaller defects. Localization was enabled by adapting odometry for conical-shaped surfaces considering additional navigation sensors. Magnets were suitable for steel towers to clamp onto the surface. A friction-based climbing ring robot (SMART— Scanning, Monitoring, Analyzing, Repair and Transportation) completed the set-up for higher payload. The maintenance period could be extended by using weather-proofed maintenance robots. The multi-robot-system was running the Robot Operating System (ROS). Additionally, first steps towards machine learning would enable maintenance staff to use pattern classification for fault diagnosis in order to operate safely from the ground in the future.
Design of a Measurement Setup for the Impedance of Low-Resistance Plate-Conductors in the RF-Range
(2006)
Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
Design and initial performance of PlanTIS: a high-resolution positron emission tomograph for plants
(2010)
Positron emitters such as 11C, 13N and 18F and their labelled compounds are widely used in clinical diagnosis and animal studies, but can also be used to study metabolic and physiological functions in plants dynamically and in vivo. A very particular tracer molecule is 11CO2 since it can be applied to a leaf as a gas. We have developed a Plant Tomographic Imaging System (PlanTIS), a high-resolution PET scanner for plant studies. Detectors, front-end electronics and data acquisition architecture of the scanner are based on the ClearPET™ system. The detectors consist of LSO and LuYAP crystals in phoswich configuration which are coupled to position-sensitive photomultiplier tubes. Signals are continuously sampled by free running ADCs, and data are stored in a list mode format. The detectors are arranged in a horizontal plane to allow the plants to be measured in the natural upright position. Two groups of four detector modules stand face-to-face and rotate around the field-of-view. This special system geometry requires dedicated image reconstruction and normalization procedures. We present the initial performance of the detector system and first phantom and plant measurements.
Purpose
To design and evaluate a four-channel cardiac transceiver coil array for functional cardiac imaging at 7T.
Materials and Methods
A four-element cardiac transceiver surface coil array was developed with two rectangular loops mounted on an anterior former and two rectangular loops on a posterior former. specific absorption rate (SAR) simulations were performed and a Burn:x-wiley:10531807:media:JMRI22451:tex2gif-stack-1 calibration method was applied prior to obtain 2D FLASH CINE (mSENSE, R = 2) images from nine healthy volunteers with a spatial resolution of up to 1 × 1 × 2.5 mm3.
Results
Tuning and matching was found to be better than 10 dB for all subjects. The decoupling (S21) was measured to be >18 dB between neighboring loops, >20 dB for opposite loops, and >30 dB for other loop combinations. SAR values were well within the limits provided by the IEC. Imaging provided clinically acceptable signal homogeneity with an excellent blood-myocardium contrast applying the Burn:x-wiley:10531807:media:JMRI22451:tex2gif-stack-2 calibration approach.
Conclusion
A four-channel cardiac transceiver coil array for 7T was built, allowing for cardiac imaging with clinically acceptable signal homogeneity and an excellent blood-myocardium contrast. Minor anatomic structures, such as pericardium, mitral, and tricuspid valves and their apparatus, as well as trabeculae, were accurately delineated.