@article{EngelmannRoethEberbecketal.2018, author = {Engelmann, Ulrich M. and Roeth, Anjali A.J. and Eberbeck, Dietmar and Buhl, Eva Miriam and Neumann, Ulf Peter and Schmitz-Rode, Thomas and Slabu, Ioana}, title = {Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {Cham}, issn = {2045-2322}, doi = {10.1038/s41598-018-31553-9}, pages = {Article number 13210}, year = {2018}, abstract = {Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95\% was achieved by depositing an intracellular total thermal energy with about 50\% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86\% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65\% after MNP were internalized inside cells.}, language = {en} } @article{EngelmannBuhlDraacketal.2018, author = {Engelmann, Ulrich M. and Buhl, Eva Miriam and Draack, Sebastian and Viereck, Thilo and Frank, and Schmitz-Rode, Thomas and Slabu, Ioana}, title = {Magnetic relaxation of agglomerated and immobilized iron oxide nanoparticles for hyperthermia and imaging applications}, series = {IEEE Magnetic Letters}, volume = {9}, journal = {IEEE Magnetic Letters}, number = {Article number 8519617}, publisher = {IEEE}, address = {New York, NY}, issn = {1949-307X}, doi = {10.1109/LMAG.2018.2879034}, year = {2018}, abstract = {Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23\% for agglomerated MNP in suspension and a decrease by up to 28\% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy.}, language = {en} } @article{ConzenAlbannaWeissetal.2018, author = {Conzen, Catharina and Albanna, Walid and Weiss, Miriam and K{\"u}rten, David and Vilser, Walthard and Kotliar, Konstantin and Z{\"a}ske, Charlotte and Clusmann, Hans and Schubert, Gerrit Alexander}, title = {Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes}, series = {Translational Stroke Research}, journal = {Translational Stroke Research}, number = {9}, publisher = {Springer Nature}, address = {Cham}, issn = {1868-601X}, doi = {10.1007/s12975-017-0585-8}, pages = {284 -- 293}, year = {2018}, abstract = {Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels—central retinal arteriolar and venular equivalent—was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.}, language = {en} } @article{DitzhausGaigall2018, author = {Ditzhaus, Marc and Gaigall, Daniel}, title = {A consistent goodness-of-fit test for huge dimensional and functional data}, series = {Journal of Nonparametric Statistics}, volume = {30}, journal = {Journal of Nonparametric Statistics}, number = {4}, publisher = {Taylor \& Francis}, address = {Abingdon}, issn = {1029-0311}, doi = {10.1080/10485252.2018.1486402}, pages = {834 -- 859}, year = {2018}, abstract = {A nonparametric goodness-of-fit test for random variables with values in a separable Hilbert space is investigated. To verify the null hypothesis that the data come from a specific distribution, an integral type test based on a Cram{\´e}r-von-Mises statistic is suggested. The convergence in distribution of the test statistic under the null hypothesis is proved and the test's consistency is concluded. Moreover, properties under local alternatives are discussed. Applications are given for data of huge but finite dimension and for functional data in infinite dimensional spaces. A general approach enables the treatment of incomplete data. In simulation studies the test competes with alternative proposals.}, language = {en} } @article{BaringhausGaigallThiele2018, author = {Baringhaus, Ludwig and Gaigall, Daniel and Thiele, Jan Philipp}, title = {Statistical inference for L²-distances to uniformity}, series = {Computational Statistics}, volume = {2018}, journal = {Computational Statistics}, number = {33}, publisher = {Springer}, address = {Berlin}, issn = {1613-9658}, doi = {10.1007/s00180-018-0820-0}, pages = {1863 -- 1896}, year = {2018}, abstract = {The paper deals with the asymptotic behaviour of estimators, statistical tests and confidence intervals for L²-distances to uniformity based on the empirical distribution function, the integrated empirical distribution function and the integrated empirical survival function. Approximations of power functions, confidence intervals for the L²-distances and statistical neighbourhood-of-uniformity validation tests are obtained as main applications. The finite sample behaviour of the procedures is illustrated by a simulation study.}, language = {en} } @article{KetelhutGoellBraunsteinetal.2018, author = {Ketelhut, Maike and G{\"o}ll, Fabian and Braunstein, Bj{\"o}rn and Albracht, Kirsten and Abel, Dirk}, title = {Comparison of different training algorithms for the leg extension training with an industrial robot}, series = {Current Directions in Biomedical Engineering}, volume = {4}, journal = {Current Directions in Biomedical Engineering}, number = {1}, publisher = {De Gruyter}, address = {Berlin}, issn = {2364-5504}, doi = {10.1515/cdbme-2018-0005}, pages = {17 -- 20}, year = {2018}, abstract = {In the past, different training scenarios have been developed and implemented on robotic research platforms, but no systematic analysis and comparison have been done so far. This paper deals with the comparison of an isokinematic (motion with constant velocity) and an isotonic (motion against constant weight) training algorithm. Both algorithms are designed for a robotic research platform consisting of a 3D force plate and a high payload industrial robot, which allows leg extension training with arbitrary six-dimensional motion trajectories. In the isokinematic as well as the isotonic training algorithm, individual paths are defined i n C artesian s pace by sufficient s upport p oses. I n t he i sotonic t raining s cenario, the trajectory is adapted to the measured force as the robot should only move along the trajectory as long as the force applied by the user exceeds a minimum threshold. In the isotonic training scenario however, the robot's acceleration is a function of the force applied by the user. To validate these findings, a simulative experiment with a simple linear trajectory is performed. For this purpose, the same force path is applied in both training scenarios. The results illustrate that the algorithms differ in the force dependent trajectory adaption.}, language = {en} } @article{WerkhausenAlbrachtCroninetal.2018, author = {Werkhausen, Amelie and Albracht, Kirsten and Cronin, Neil J and Paulsen, G{\o}ran and Bojsen-M{\o}ller, Jens and Seynnes, Olivier R}, title = {Effect of training-induced changes in achilles tendon stiffness on muscle-tendon behavior during landing}, series = {Frontiers in physiology}, journal = {Frontiers in physiology}, number = {9}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-042X}, doi = {10.3389/fphys.2018.00794}, pages = {11 Seiten}, year = {2018}, abstract = {During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18\%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8\%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21\%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation.}, language = {en} } @article{RabehiGarlanAchtsnichtetal.2018, author = {Rabehi, Amine and Garlan, Benjamin and Achtsnicht, Stefan and Krause, Hans-Joachim and Offenh{\"a}usser, Andreas and Ngo, Kieu and Neveu, Sophie and Graff-Dubois, Stephanie and Kokabi, Hamid}, title = {Magnetic detection structure for Lab-on-Chip applications based on the frequency mixing technique}, series = {Sensors}, volume = {18}, journal = {Sensors}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {1424-8220}, doi = {10.3390/s18061747}, pages = {14 Seiten}, year = {2018}, abstract = {A magnetic frequency mixing technique with a set of miniaturized planar coils was investigated for use with a completely integrated Lab-on-Chip (LoC) pathogen sensing system. The system allows the detection and quantification of superparamagnetic beads. Additionally, in terms of magnetic nanoparticle characterization ability, the system can be used for immunoassays using the beads as markers. Analytical calculations and simulations for both excitation and pick-up coils are presented; the goal was to investigate the miniaturization of simple and cost-effective planar spiral coils. Following these calculations, a Printed Circuit Board (PCB) prototype was designed, manufactured, and tested for limit of detection, linear response, and validation of theoretical concepts. Using the magnetic frequency mixing technique, a limit of detection of 15 µg/mL of 20 nm core-sized nanoparticles was achieved without any shielding.}, language = {en} } @article{AlbannaKotliarLuekeetal.2018, author = {Albanna, Walid and Kotliar, Konstantin and L{\"u}ke, Jan Niklas and Alpdogan, Serdar and Conzen, Catharina and Lindauer, Ute and Clusmann, Hans and Hescheler, J{\"u}rgen and Vilser, Walthard and Schneider, Toni and Schubert, Gerrit Alexander}, title = {Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis}, series = {Plos one}, volume = {13}, journal = {Plos one}, number = {10}, publisher = {PLOS}, address = {San Francisco}, doi = {10.1371/journal.pone.0204689}, pages = {e0204689}, year = {2018}, abstract = {Background Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC. Methods A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed. Results A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001). Conclusions To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals.}, language = {en} }