Kinetic Analysis of dynamic MP4A PET Scans of Human Brain using Voxel based Nonlinear Least Squares Fitting

Dynamic PET (Positron Emission Tomography) involving a number of radiotracers is an established technique for in vivo estimation of biochemical parameters in human brain, such as the overall metabolic rate and certain receptor concentrations or enzyme activities. 11C labeled methyl-4-piperidyl acetate (MP4A) and -propionate (MP4P) are established radiotracers for measuring activity of acetylcholine esterase (AChE), which relates to functionality of the cholinergic system. MP4A kinetic analysis without arterial blood sampling employs a reference tissue based "irreversible tracer model". Implementations can be region or voxel based, in the second case providing parametric images of k3 which is an indicator of AChE activity. This work introduces an implementation of voxel based kinetic analysis using weighted Nonlinear Least Squares fitting (NLS), which is fast enough for standard PCs. The entire workflow leading from reconstructed PET scans to parametric images of k3, including normalization and correction for patient movement, has been automatized. Image preprocessing has been redefined and fixed masks are no longer required. A focus of this work is error estimation of k3 at the voxel and regional level. A formula is derived for voxel based estimation of random error, it is based on residual weighted squared differences and has been successfully validated against simulated data. The reference curves turned out to be the main source of errors in regional mean values of k3. Major improvements were reached in this area by switching from fixed to adaptive Putamen masks and raising their volume from 5.4 to 12.5 or 16 ml. Also, a method for correcting reference curves obtained from nonideal reference tissues is presented. For the improved implementation, random error of the mean k3 of a number of cerebral regions has been assessed based on PET studies of 12 human subjects, by splitting them in two independent data sets at the sinogram level. According to this sample, absolute standard errors of 0.0012 in most cortex regions and 0.0053 in Hippocampus are induced by noise of voxel based activity curves, while errors of approximately 0.0025 and 0.0050 are induced by noise of the reference curves. Different types of systematic as well as noise-induced bias have been investigated by simulations; their combined effect on the computed k3 was found below 3 percent. The implementation is available as a modul of the VINCI software package and has been used in clinical studies on Parkinson's Disease and Alzheimer Dementia

Full- & Reduced-Order State-Space Modeling of Wind Turbine Systems with Permanent-Magnet Synchronous Generator

Wind energy is an integral part of nowadays energy supply and one of the fastest growing sources of electricity in the world today. Accurate models for wind energy conversion systems (WECSs) are of key interest for the analysis and control design of present and future energy systems. Existing control-oriented WECSs models are subject to unstructured simplifications, which have not been discussed in literature so far. Thus, this technical note presents are thorough derivation of a physical state-space model for permanent magnet synchronous generator WECSs. The physical model considers all dynamic effects that significantly influence the system's power output, including the switching of the power electronics. Alternatively, the model is formulated in the $(a,b,c)$- and $(d,q)$-reference frame. Secondly, a complete control and operation management system for the wind regimes II and III and the transition between the regimes is presented. The control takes practical effects such as input saturation and integral windup into account. Thirdly, by a structured model reduction procedure, two state-space models of WECS with reduced complexity are derived: a non-switching model and a non-switching reduced-order model. The validity of the models is illustrated and compared through a numerical simulation study.Comment: 23 pages, 11 figure

Non-linear MPC for winding loss optimised torque control of anisotropic PMSM

For a non-linear anisotropic permanent magnet synchronous machine (PMSM), a prediction model for model predictive control (MPC) considering effects like cross-coupling and saturation is developed in a straight forward procedure. The objective of the designed MPC is either tracking of reference currents or torque tracking. Both approaches use the projected fast gradient method (PFGM) as optimisation algorithm. The latter approach makes look-up-tables for current references obsolete and additionally minimises winding losses. This two approaches are compared in a simulation study with a state of the art PI controller

Interaction of Glia Cells with Glioblastoma and Melanoma Cells under the Influence of Phytocannabinoids

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30–40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell–cell interactions in a 3D model. Furthermore, the effects of phytocannabinoids, cannabidiol (CBD), tetrahydrocannabidiol (THC), or their co-application were analyzed. Co-culture of tumor cells with glial cells had little effect on 3D spheroid formation, while treatment with cannabinoids led to significantly larger spheroids. The addition of astrocytes blocked cannabinoid-induced effects. None of the interventions affected cell death. Furthermore, glial cell-conditioned media led to a significant slowdown in collective, but not single-cell migration speed. Taken together, glial cells in glioblastoma and brain metastasis micromilieu impact the tumor spheroid formation, cell spreading, and motility. Since the size of spheroid remained unaffected in glial cell tumor co-cultures, phytocannabinoids increased the size of spheroids without any effects on migration. This aspect might be of relevance since phytocannabinoids are frequently used in tumor therapy for side effects

Full- and Reduced-Order State-Space Modeling of Wind Turbine Systems with Permanent Magnet Synchronous Generator

Full-order state-space models represent the starting point for the development of advanced control methods for wind turbine systems (WTSs). Regarding existing control-oriented WTS models, two research gaps must be noted: (i) There exists no full-order WTS model in form of one overall ordinary differential equation that considers all dynamical effects which significantly influence the electrical power output; (ii) all existing reduced-order WTS models are subject to rather arbitrary simplifications and are not validated against a full-order model. Therefore, in this paper, two full-order nonlinear state-space models (of 11th and 9th-order in the (a, b, c)- and (d, q)-reference frame, resp.) for variable-speed variable-pitch permanent magnet synchronous generator WTSs are derived. The full-order models cover all relevant dynamical effects with significant impact on the system’s power output, including the switching behavior of the power electronic devices. Based on the full-order models, by a step-by-step model reduction procedure, two reduced-order WTS models are deduced: A non-switching (averaging) 7th-order WTS model and a non-switching 3rd-order WTS model. Comparative simulation results reveal that all models capture the dominant system dynamics properly. The full-order models allow for a detailed analysis covering the high frequency oscillations in the instantaneous power output due to the switching in the power converters. The reduced-order models provide a time-averaged instantaneous power output (which still correctly reflects the energy produced by the WTS) and come with a drastically reduced complexity making those models appropriate for large-scale power grid controller design

Diversity-Oriented Synthesis of [2.2]Paracyclophane-derived Fused Imidazo[1,2-a]heterocycles by Groebke-Blackburn-Bienayme Reaction : Accessing Cyclophanyl Imidazole Ligands Library

This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienayme three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation.Peer reviewe

Diversity-Oriented Synthesis of [2.2]Paracyclophane-derived Fused Imidazo[1,2-a]heterocycles by Groebke-Blackburn-Bienaymé Reaction: Accessing Cyclophanyl Imidazole Ligands Library

This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation