On the role of arkypallidal and prototypical neurons for phase transitions in the external pallidum. - In: The journal of neuroscience, ISSN 1529-2401, Bd. 41 (2021), 31, S. 6673-6683
The external pallidum (globus pallidus pars externa [GPe]) plays a central role for basal ganglia functions and dynamics and, consequently, has been included in most computational studies of the basal ganglia. These studies considered the GPe as a homogeneous neural population. However, experimental studies have shown that the GPe contains at least two distinct cell types (prototypical and arkypallidal cells). In this work, we provide in silico insight into how pallidal heterogeneity modulates dynamic regimes inside the GPe and how they affect the GPe response to oscillatory input. We derive a mean-field model of the GPe system from a microscopic spiking neural network of recurrently coupled prototypical and arkypallidal neurons. Using bifurcation analysis, we examine the influence of dopamine-dependent changes of intrapallidal connectivity on the GPe dynamics. We find that increased self-inhibition of prototypical cells can induce oscillations, whereas increased inhibition of prototypical cells by arkypallidal cells leads to the emergence of a bistable regime. Furthermore, we show that oscillatory input to the GPe, arriving from striatum, leads to characteristic patterns of cross-frequency coupling observed at the GPe. Based on these findings, we propose two different hypotheses of how dopamine depletion at the GPe may lead to phase-amplitude coupling between the parkinsonian beta rhythm and a GPe-intrinsic y rhythm. Finally, we show that these findings generalize to realistic spiking neural networks of sparsely coupled Type I excitable GPe neurons. - SIGNIFICANCE STATEMENT Our work provides (1) insight into the theoretical implications of a dichotomous globus pallidus pars externa (GPe) organization, and (2) an exact mean-field model that allows for future investigations of the relationship between GPe spiking activity and local field potential fluctuations. We identify the major phase transitions that the GPe can undergo when subject to static or periodic input and link these phase transitions to the emergence of synchronized oscillations and cross-frequency coupling in the basal ganglia. Because of the close links between our model and experimental findings on the structure and dynamics of prototypical and arkypallidal cells, our results can be used to guide both experimental and computational studies on the role of the GPe for basal ganglia dynamics in health and disease.
https://doi.org/10.1523/JNEUROSCI.0094-21.2021
Automatic segmentation of skin cells in multiphoton data using multi-stage merging. - In: Scientific reports, ISSN 2045-2322, Bd. 11 (2021), 14534, S. 1-19
We propose a novel automatic segmentation algorithm that separates the components of human skin cells from the rest of the tissue in fluorescence data of three-dimensional scans using non-invasive multiphoton tomography. The algorithm encompasses a multi-stage merging on preprocessed superpixel images to ensure independence from a single empirical global threshold. This leads to a high robustness of the segmentation considering the depth-dependent data characteristics, which include variable contrasts and cell sizes. The subsequent classification of cell cytoplasm and nuclei are based on a cell model described by a set of four features. Two novel features, a relationship between outer cell and inner nucleus (OCIN) and a stability index, were derived. The OCIN feature describes the topology of the model, while the stability index indicates segment quality in the multi-stage merging process. These two new features, combined with the local gradient magnitude and compactness, are used for the model-based fuzzy evaluation of the cell segments. We exemplify our approach on an image stack with 200 × 200 × 100 [my]m^3, including the skin layers of the stratum spinosum and the stratum basale of a healthy volunteer. Our image processing pipeline contributes to the fully automated classification of human skin cells in multiphoton data and provides a basis for the detection of skin cancer using non-invasive optical biopsy.
https://doi.org/10.1038/s41598-021-93682-y
Normative data and standard operating procedures for static and dynamic retinal vessel analysis as biomarker for cardiovascular risk. - In: Scientific reports, ISSN 2045-2322, Bd. 11 (2021), 14136, S. 1-12
Retinal vessel phenotype is predictive for cardiovascular outcome. This cross-sectional population-based study aimed to quantify normative data and standard operating procedures for static and dynamic retinal vessel analysis. We analysed central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents, as well as retinal endothelial function, measured by flicker light‐induced maximal arteriolar (aFID) and venular (vFID) dilatation. Measurements were performed in 277 healthy individuals aged 20 to 82 years of the COmPLETE study. The mean range from the youngest compared to the oldest decade was 196 ± 13 to 166 ± 17 µm for CRAE, 220 ± 15 to 199 ± 16 µm for CRVE, 3.74 ± 2.17 to 3.79 ± 2.43% for aFID and 4.64 ± 1.85 to 3.86 ± 1.56% for vFID. Lower CRAE [estimate (95% CI): - 0.52 (- 0.61 to - 0.43)], CRVE [- 0.33 (- 0.43 to - 0.24)] and vFID [- 0.01 (- 0.26 to - 0.00)], but not aFID, were significantly associated with older age. Interestingly, higher blood pressure was associated with narrower CRAE [- 0.82 (- 1.00 to - 0.63)] but higher aFID [0.05 (0.03 to 0.07)]. Likewise, narrower CRAE were associated with a higher predicted aFID [- 0.02 (- 0.37 to - 0.01)]. We recommend use of defined standardized operating procedures and cardiovascular risk stratification based on normative data to allow for clinical implementation of retinal vessel analysis in a personalized medicine approach.
https://doi.org/10.1038/s41598-021-93617-7
Using the multi-linear rank-(Lr, Lr, 1) decomposition for the detection of the 200 Hz band activity in somatosensory evoked magnetic fields and somatosensory evoked electrical potentials. - In: IEEE access, ISSN 2169-3536, Bd. 9 (2021), S. 106232-106244
Im Titel ist "r" tiefgestellt
https://doi.org/10.1109/ACCESS.2021.3100759
Reactive auto-completion of modeling activities. - In: IEEE transactions on software engineering, ISSN 1939-3520, Bd. 47 (2021), 7, S. 1431-1451
Assisting and automating software engineering tasks is a state-of-the-art way to support stakeholders of development projects. A common assistance function of IDEs is the auto-completion of source code. Assistance functions, such as auto-completion, are almost entirely missing in modeling tools though auto-completion in general gains continuously more importance in software development. We analyze a user’s performed editing operations in order to anticipate modeling activities and to recommend appropriate auto-completions for them. Editing operations are captured as events and modeling activities are defined as complex event patterns, facilitating the matching by complex-event-processing. The approach provides adapted auto-completions reactively upon each editing operation of the user. We implemented the RapMOD prototype as add-in for the modeling tool Sparx Enterprise Architect™ . A controlled user experiment with 37 participants performing modeling tasks demonstrated the approach's potential to reduce modeling effort significantly. Users having auto-completions available for a modeling scenario performed the task 27 percent faster, needed to perform 56 percent less actions, and perceived the task 29 percent less difficult.
https://doi.org/10.1109/TSE.2019.2924886
Defocus particle tracking : a comparison of methods based on model functions, cross-correlation, and neural networks. - In: Measurement science and technology, ISSN 1361-6501, Bd. 32 (2021), 9, 094011, insges. 14 S.
Defocus particle tracking (DPT) has gained increasing importance for its use to determine particle trajectories in all three dimensions with a single-camera system, as typical for a standard microscope, the workhorse of todays ongoing biomedical revolution. DPT methods derive the depth coordinates of particle images from the different defocusing patterns that they show when observed in a volume much larger than the respective depth of field. Therefore it has become common for state-of-the-art methods to apply image recognition techniques. Two of the most commonly and widely used DPT approaches are the application of (astigmatism) particle image model functions (MF methods) and the normalized cross-correlations between measured particle images and reference templates (CC methods). Though still young in the field, the use of neural networks (NN methods) is expected to play a significant role in future and more complex defocus tracking applications. To assess the different strengths of such defocus tracking approaches, we present in this work a general and objective assessment of their performances when applied to synthetic and experimental images of different degrees of astigmatism, noise levels, and particle image overlapping. We show that MF methods work very well in low-concentration cases, while CC methods are more robust and provide better performance in cases of larger particle concentration and thus stronger particle image overlap. The tested NN methods generally showed the lowest performance, however, in comparison to the MF and CC methods, they are yet in an early stage and have still great potential to develop within the field of DPT.
https://doi.org/10.1088/1361-6501/abfef6
Surface-modified magnetite nanoparticles affect lysozyme amyloid fibrillization. - In: Biochimica et biophysica acta, ISSN 1872-8006, Bd. 1865 (2021), 9, 129941, insges. 9 S.
Background - The surface of nanoparticles (NPs) is an important factor affecting the process of poly/peptides' amyloid aggregation. We have investigated the in vitro effect of trisodium citrate (TC), gum arabic (GA) and citric acid (CA) surface-modified magnetite nanoparticles (COAT-MNPs) on hen egg-white lysozyme (HEWL) amyloid fibrillization and mature HEWL fibrils. - Methods - Dynamic light scattering (DLS) was used to characterize the physico-chemical properties of studied COAT-MNPs and determine the adsorption potential of their surface towards HEWL. The anti-amyloid properties were studied using thioflavin T (ThT) and tryptophan (Trp) intrinsic fluorescence assays, and atomic force microscopy (AFM). The morphology of amyloid aggregates was analyzed using Gwyddion software. The cytotoxicity of COAT-MNPs was determined utilizing Trypan blue (TB) assay. - Results - Agents used for surface modification affect the COAT-MNPs physico-chemical properties and modulate their anti-amyloid potential. The results from ThT and intrinsic fluorescence showed that the inhibitory activities result from the more favorable interactions of COAT-MNPs with early pre-amyloid species, presumably reducing nuclei and oligomers formation necessary for amyloid fibrillization. COAT-MNPs also possess destroying potential, which is presumably caused by the interaction with hydrophobic residues of the fibrils, resulting in the interruption of an interface between [beta]-sheets stabilizing the amyloid fibrils. - Conclusion - COAT-MNPs were able to inhibit HEWL fibrillization and destroy mature fibrils with different efficacy depending on their properties, TC-MNPs being the most potent nanoparticles. - General significance - The study reports findings regarding the general impact of nanoparticles' surface modifications on the amyloid aggregation of proteins.
https://doi.org/10.1016/j.bbagen.2021.129941
T2- and T1 relaxivities and magnetic hyperthermia of iron-oxide nanoparticles combined with paramagnetic Gd complexes. - In: Journal of chemical sciences, ISSN 0973-7103, Bd. 133 (2021), 2, 43, insges. 10 S.
Im Titel sind "2-" und "1" tiefgestellt
The present paper reports the synthesis of iron-oxide nanoparticles (diameter 12.8±2.2 nm) coated with silica shell doped with paramagnetic Gd(III)-based complexes. The resulting nanoparticles with a silica shell thickness of about 45 nm have an average diameter of 113.1±14.3 nm and feature high transverse and longitudinal relaxivities (356 and 25 mM^-1 s^-1, respectively) at 1.5 T and 25 ˚C on a medical whole body NMR scanner. It has been also revealed using magnetic heating measurements that the prepared core-shell nanoparticles possess a high specific adsorption rate of around 236 W/g in aqueous media. The surface of the composite nanoparticles was decorated by amino-groups for a greater cellular uptake behaviour. The cell viability measurements reveal the concentration-dependent cytotoxicity of the nanoparticles, which agrees well with the high content of Gd(III) complexes in the nanomaterial. The obtained results show that the core-shell design of nanoparticles with superparamagnetic and paramagnetic parts can be promising for high transverse (and longitudinal) relaxivity as well as magnetic hyperthermia.
https://doi.org/10.1007/s12039-021-01904-7
Hydroxyapatite-coated SPIONs and their influence on cytokine release. - In: International journal of molecular sciences, ISSN 1422-0067, Bd. 22 (2021), 8, 4143, S. 1-19
Richtiger Name des 7. Verfassers: Aldo R. Boccacccini
Hydroxyapatite- or calcium phosphate-coated iron oxide nanoparticles have a high potential for use in many biomedical applications. In this study, a co-precipitation method for the synthesis of hydroxyapatite-coated nanoparticles (SPIONHAp), was used. The produced nanoparticles have been characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, Fourier transform infrared spectrometry, atomic emission spectroscopy, scanning electron microscopy, transmission electron microscopy, selected area diffraction, and energy-dispersive X-ray spectroscopy. The results showed a successful synthesis of 190 nm sized particles and their stable coating, resulting in SPIONHAp. Potential cytotoxic effects of SPIONHAp on EL4, THP-1, and Jurkat cells were tested, showing only a minor effect on cell viability at the highest tested concentration (400 [my]g Fe/mL). The results further showed that hydroxyapatite-coated SPIONs can induce minor TNF-α and IL-6 release by murine macrophages at a concentration of 100 [my]g Fe/mL. To investigate if and how such particles interact with other substances that modulate the immune response, SPIONHAp-treated macrophages were incubated with LPS (lipopolysaccharides) and dexamethasone. We found that cytokine release in response to these potent pro- and anti-inflammatory agents was modulated in the presence of SPIONHAp. Knowledge of this behavior is important for the management of inflammatory processes following in vivo applications of this type of SPIONs.
https://doi.org/10.3390/ijms22084143
Quantitative interpretation of UWB radar images for non-invasive tissue temperature estimation during hyperthermia. - In: Diagnostics, ISSN 2075-4418, Bd. 11 (2021), 5, 818, insges. 16 S.
The knowledge of temperature distribution inside the tissue to be treated is essential for patient safety, workflow and clinical outcomes of thermal therapies. Microwave imaging represents a promising approach for non-invasive tissue temperature monitoring during hyperthermia treatment. In the present paper, a methodology for quantitative non-invasive tissue temperature estimation based on ultra-wideband (UWB) radar imaging in the microwave frequency range is described. The capabilities of the proposed method are demonstrated by experiments with liquid phantoms and three-dimensional (3D) Delay-and-Sum beamforming algorithms. The results of our investigation show that the methodology can be applied for detection and estimation of the temperature induced dielectric properties change.
https://doi.org/10.3390/diagnostics11050818