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Characterization of testosterone and androgen receptor action in human and rhesus macaque heart muscle cells
Androgens are sex steroid hormones that influence various processes in reproductive tissues and peripheral organs. Their lipophilic nature enables free diffusion through the plasma membrane. In the cytoplasm, testosterone (T) binds to its receptor, the androgen receptor (AR), and the complex then translocates to the nucleus for activation or inhibition of gene expression. Although the effects of androgens are studied greatly in healthy and diseased reproductive tissues, little is known about their cellular and molecular action in the cardiovascular system. Clinical research reported the impact of high and low T levels on the human heart and vasculature, but the data are currently conflicting. Additionally, most of the molecular and cellular processes triggered by androgens in heart muscle cells were researched using rodents. These models vastly contributed to our understanding of biological processes, though are partially limited due to differences in heart physiology to humans. This work focused on studying the impact of male physiological (25 nM) and supraphysiological (100 nM) concentrations of T on primate cardiomyocytes (CMs) of human and rhesus macaque origin. For the first time, AR was detected in CM nuclei of male rhesus macaque tissue. Notably, no signal was detected in female heart cells. For further in vitro studies we used an induced pluripotent stem cell (iPSC) model. AR was detected in human and rhesus macaque iPSCs and was induced and translocated by T. A directed cardiac differentiation protocol was optimized and used to generate CMs from male and female human and rhesus macaque cell lines. Non-treated cells showed cytoplasmic AR staining while T-treated cells displayed mostly nuclear signals. T treatment induced AR abundance in male rhesus iPSCs and iPSC-CMs. Interestingly, we detected an AR-V7 isoform with no T-binding capabilities in human iPSC-CMs and human left ventricular tissue. Since T may also exhibit AR-independent action, we generated a clonal AR knock-out (KO) human male iPSC line to investigate AR-independent effects. Further analysis of the AR KO cell line showed fewer CMs generated after differentiation, a higher proliferation rate, and a more disorganized contractile apparatus compared with wild-type (WT) cells. The analysis of differentially expressed genes in KO and WT cells further highlighted a more immature state of KO CMs. While 24 hours of T treatment resulted in a decrease in Ca2+ current density, 48 hours of exposure did not result in significant changes between treated and non- treated groups of WT cells. Overall, the data has shown a more drastic effect of the AR KO itself than T treatment. That is why we hypothesized T conversion to other androgens. LC- MS/MS analysis demonstrated low levels of T in cell culture media 48 hours after T addition confirming our assumption. Moreover, androstenedione, a weaker androgen than T, was detected in human samples, but almost none in rhesus. In conclusion, this work demonstrates relevant effects of the T / AR system on proliferation, cytoskeleton organization, electrophysiological parameters, and gene expression of primate CMs.2024-04-0
Trophic ecology of earthworms: the relative role of litter- and root-derived resources investigated with compound-specific stable isotope analysis of amino acids
Earthworms, known as ecosystem engineers, shape the structure and functioning of ecosystems by altering nutrient cycling, habitat architecture and plant growth due to feeding interactions or physiological activities. They play a central role in soil food webs due to their high biomass. However, despite their ecological importance, the trophic niches of earthworms to date remain controversial. This largely limits the reconstruction of soil food web topology and the understanding of belowground processes. Earthworms are typically assumed to be fuelled by brown energy, i.e., dead plant litter. However, there is growing evidence that root-derived resources as the ‘green’ energy channel in soil food webs are of significant importance. Using resource manipulation experiments, this dissertation investigated the role of root- and litter-derived resources of different quality to earthworm nutrition and how earthworms in turn affect the plant performance. Further, the effect of different cropping systems on the incorporation of root-derived C and mineral N by earthworms and centipedes was explored based on a labelling experiment. In addition, I tested if the variation of trophic niches of earthworms further propagates to higher trophic levels using centipedes as representatives of major macrofauna predators.
Chapter two investigates the dietary contribution of root-derived resources of differing quality (grasses, legumes) to the nutrition of earthworms by combining bulk and compound-specific amino acid stable isotope analysis. The results suggest that root-derived resources contribute to earthworm nutrition primarily via the bacterial channel. Direct contribution of plants to earthworm nutrition averaged 30% and was enhanced by legume monoculture and mixed cultures. The results provide novel insights into interactions between plant roots and detritivore soil animals and shed light on the contribution of ‘green’ energy to the nutrition of soil macro-detritivores. This study also challenges the view that the fungal energy channel dominates in soil food webs.
Chapter three tests the effects of earthworm species (epigeic, anecic and endogeic) on plant performance of differing functional groups in monoculture and mixture. Plant mixture promoted the growth of both legumes and grasses, likely via complementary nitrogen use and alleviated intraspecific competition. Additionally, grass fuelled the activity of soil microorganisms by root exudation, likely benefiting legume nitrogen fixation. Earthworm species differentially affected nitrogen uptake by grasses, with epigeic and endogeic species facilitating nitrogen uptake of grasses more than anecic species, especially in grass monocultures. While underlining the potential of legume-grass mixture in improving plant nitrogen uptake and productivity, the results also highlight the role of earthworms in altering and improving the uptake of nitrogen by grass from different pools in soil. These findings suggest that epigeic and endogeic earthworms may be able to improve performance of grass monocultures, with potential implications for future agricultural management strategies.
Chapter four uncovers the dietary contribution of litter-derived resources of differing quality to earthworm species of different ecological groups (epigeic, anecic and endogeic) using bulk and compound-specific amino acid stable isotope analysis. Litter resources contributed to earthworm nutrition mainly via the bacterial channel, but that this varied with earthworm ecological groups. Direct contribution of plant-derived resources to earthworm nutrition averaged 30%, but higher litter quality shifted the channelling of resources from the bacterial to the plant energy channel, suggesting important functional shifts in soil food webs in response to higher litter quality.
Chapter five explores the effects of cropping system (rape, grass, willow) on the incorporation of root-derived C and mineral N by earthworms (epigeic, anecic and endogeic) and centipedes based on a combination of 13C pulse-labelling of plants and 15N labelling of soil and using analyses of bulk stable isotopes and compound-specific stable isotopes of amino acids. Across all cropping systems, anecic and epigeic earthworms incorporated more root-derived C than endogeic earthworms, supporting the notion that endogeic earthworms mainly rely on older soil organic matter. Compared to willow, the grass and rape only allowed faster root-derived C flux to anecic earthworms and centipedes, while coupling between root-derived C and mineral N incorporation by all soil animals was stronger in grass and rape either due to the direct use of plant root-derived resources or of root-associated microorganisms. In willow, the use of plant root-derived resources also facilitated the coupling of root-derived C and mineral N assimilation by anecic earthworms. Supporting the ‘trophic whales’ notion, earthworms were not the intermediate link in transferring the root-derived C and mineral N to centipedes as higher trophic level predators. Rather, soil mesofauna collembolans appeared to be the main mediator in simultaneously conveying root-derived C and mineral N to centipedes. Together, this study demonstrates joint effects of cropping system and ecological group of soil animals in modulating the fluxes of root-derived C and mineral N to the soil food web.
Overall, this dissertation highlights that soil decomposer animals play key functional roles in linking green and brown energy via multiple energy channels, and that plant-based resources of different quality/identity alter the coupling of these energy channels. In turn, soil decomposer animals also enhance the nutrient uptake by plants via different nitrogen pools in soil, and thus improve the performance of plant monocultures, suggesting potential implications for sustainable agricultural management strategies.2024-07-3
Evaluating a Collection of Agronomic Traits to Better Understand the Importance of Epistasis and Epistasis by Environment Interaction in Maize.
General Directorate of Education Abroad (Yurt Dışı Eğitim Genel Müdürlüğü) Ministry of Education, Republic of Türkiye.Maize, a key cereal crop, stands alongside wheat and rice in global importance. Its domestication from teosinte in southern Mexico 10,000 years ago marked a turning point in human agriculture. Over the centuries, maize has spread globally, becoming a staple crop vital for food, feed, and biofuel. Modern plant breeding techniques and improved genetic backgrounds have propelled maize production, making it adaptable to diverse environments and significantly contributing to global food security.
The increase in agronomic traits owes to multiple factors, including advancements in plant genetics, agronomic practices, and technological innovations. Agronomic practices, precision agriculture, and remote sensing contribute to higher yields, underscoring the multidimensional approach to crop improvement. Molecular markers and genomic selection enable breeders to identify genes controlling crucial agronomic traits like yield, flowering time, and plant height. Genetic markers, especially single nucleotide polymorphisms (SNPs), have been pivotal in developing improved maize varieties.
The integration of sequencing technology has revolutionized plant breeding, making genetic information more accessible. The decreasing cost of sequencing has facilitated genome exploration, enabling the identification of genes controlling agronomic traits.
Furthermore, researchers have identified that additive genetic variation predominantly contributes to the variation within a population. However, it is acknowledged that additive variation does not fully account for heritability, leaving a portion known as missing heritability. Consequently, an increasing number of studies are directing their focus toward understanding and incorporating this missing heritability to enhance the prediction of quantitative agronomic traits. Epistasis, representing complex interactions between genes, is one approach employed to calculate this missing heritability. However, detecting epistatic interactions poses challenges, notably the multiple testing problem. Additionally, environmental factors can modify gene effects, complicating their detection. To address these complexities and identify epistatic interactions while considering the impact of the environment on genotypes, a unique population must be tested across various environments.
The initial study aimed to identify epistasis by environment interactions using genomes-to-field (G2F) data tested in multiple environments. In the second study, we aimed to investigate origin-of-seed effects utilizing an Epistasis Mapping Population (EMP).
Epistasis by environment (EEI) study delves into the complicated relationships between various agronomic traits in maize, exploring correlations, heritability, and quantitative trait loci (QTL) mapping across multiple environments to find the interactions between QTLs, QTLs by environment, and epistasis by environment interactions. The research investigated the following quantitative traits: pollination and silking days, plant and ear height, stand percentage, and yield. The initial analysis reveals strong correlations between pollen and silk days after pollination (DAP), as well as between plant height (PH) and ear height (EH). Moderate correlations exist among PH, EH, pollen DAP, and silk DAP, indicative of the intricate network of influences among these quantitative traits. Interestingly, the stand percentage exhibits a low correlation with other traits across locations, suggesting its sensitivity to external factors during the growing period. The subsequent QTL mapping analysis uncovers significant loci associated with the studied traits across environments. These findings align with previous research, emphasizing the genetic complexity of traits. Notably, the study identifies specific QTLs for each trait in different locations, underlining the substantial impact of environmental factors on trait expression. Our analysis extends to QTL-environment interactions, revealing location-specific markers and significant interactions for pollen DAP, silk DAP, PH, EH, and yield. This underscores the importance of considering the environment when interpreting genetic influences on these traits.
Moreover, we identified significant epistatic interactions for each phenotypic trait. The following analysis introduces the concept of epistasis by environment interactions (EEI), illustrating pollen and silk DAP, PH, EH, and yield. EEI study comprehensively illustrates the genetic and environmental factors influencing agronomic traits in maize. Our research contributes valuable insights that can inform future breeding strategies and enhance our understanding of maize phenotypic traits' complex genetic and environmental interactions.
In the second study, we utilized two diverse seed sources of Epistasis Mapping Populations (EMPs), which aim to identify epistatic interactions between genomic regions, to investigate origin-of-seed effects on mRNA levels. By comparing phenotypic performances, EMP helps identify regions of the genome where epistasis occurs, contributing valuable insights into gene regulation and species evolution. EMPs reduce the multiple-testing and provide a nuanced understanding of gene interactions. The study focused on the influence of origin-of-seed on maize seedlings at the V2 growth stage with EMPs. While complete sets of EMPs are traditionally required for studying epistatic interactions, the study uses a subset of genotypes in this part of the research question.
Our study found no differentially expressed genes (DEGs) between two seed sources at the V2 growing stage. Despite limitations, such as a small sample size and focusing solely on mRNA expression, the study suggests that greenhouse and field environmental conditions do not significantly impact the progeny's gene expression at the V2 growing stage. In addition, robust comparisons between different genotypes validate the reliability of the analysis, reinforcing the conclusion that origin-of-seed effects do not lead to significant expression. Overall, this research contributes valuable insights into the origin-of-seed effect on maize seedlings, pointing out a direction for further investigations.2024-04-1
Bone changes in cranial vaults of a contemporary population of body donors from the Anatomy Center of the University Medical Center Göttingen: A contribution to paleopathology.
Many works in the field of geriatrics and gerontology have focused on the anatomical, physiological, and biochemical changes in the aging organism and their mutual influence. However, in paleopathological research, aside from degenerative changes, this topic represents a gap. Distinguishing between physiological, purely age-related, non-pathological changes and pathological changes is often difficult due to their mutual influence—especially in archaeological bone finds, where this distinction is often complicated by postmortem changes. Against this background, the question arose as to whether such age-related physiological and pathological changes are present in a contemporary population and how they manifest. Furthermore, the question arose of whether it is possible to differentiate between physiological age-related changes and pathological changes based on morphological findings, and whether these changes show a dependence on age and sex. Also of interest was the extent to which these changes mutually influence their morphological appearance. In order to contribute to anthropological-paleopathological assessment, the pathomechanisms and diseases underlying bone changes were made plausible. For this purpose, 616 skullcaps from body donations that died between 1985 and 2005 were examined for bony changes. In order to do justice to the entire extent of bone changes on the skull roof, the results of macroscopic, microscopic, and radiological findings were presented and detailed in selected case examples. A variety of images were used in the work to facilitate the comparison of findings on archaeological bone finds. Regarding age, statistical relevance could not be demonstrated due to the mostly small sample size of affected individuals and a generally insufficient representation of younger individuals. In most cases, a balanced distribution of sexes could be demonstrated. An exception was found in the frequency of enlarged impressions of meningeal vessels and the associated neoplasia in the marginal area of meningeal vessels and traces of perisinuous processes. In these cases, women were statistically significantly more affected by these changes than men. The bone changes were also discussed against the background of metabolic, structural, and immunological aging changes to demonstrate their diverse interplay mechanisms. In summary, it must be said that in the discussion of bone changes, there often appears to be a blurry boundary between the physiological and the pathological. It was shown that bone changes such as substance loss, neoplasia, and traces of hypervascularization, which are primarily associated with pathological processes, can often be strongly influenced by the effects of physiological aging changes. Consequently, it is worth discussing whether these changes could be age-related bone modulations. This is a matter that requires further study for subsequent clarification.2024-06-1
Action understanding and prediction during inter-agent interaction
The utilisation of robotics has seen a significant rise over the years, particularly fuelled by the burgeoning advancements in deep learning and artificial intelligence research and development. Despite this progress, the challenge of social acceptance remains a significant
hurdle in the widespread adoption of robots for practical applications. A prominent aspect of this challenge lies in the effectiveness and naturalness of HRI (Human-Robot Interaction). Enhancing robotic behaviours holds considerable potential to substantially improve the social
acceptance of robots. The approach to achieve the enhancement of HRI of this research is by firstly obtaining a profound comprehension of human behaviours in interactive situations of HHI (Human-Human Interaction). Subsequently, the research will use the unveiled insights and
principles to guide the design, evolution, and implementation of socially adept robots.
The research begins by crafting experiment paradigms centred on the concept of "double contingency," which is a term stands for a social situation that the agents perceive each other without having prior knowledge about the forthcoming events. Across the study, three distinct
experiment games are designed to simulate diverse interaction scenarios. Game 1 delves into competitive contexts, employing the do/undo paradigm and assigning two player roles: leader and follower. It challenges follower players to keenly observe the actions of the leader player
and counteract accordingly. Game 2 and Game 3 target collaborative scenarios, where two players are tasked with constructing a predefined combination of objects while constrained to act simultaneously.
Subsequently, the research targets at implementing a sophisticated experiment setup capable of capturing details of human behaviour patterns during interaction. Eye movement, touching/untouching events and hand movement are the three major types of data in this research. The
successful implementations have enabled the experiment setup to effectively and sufficiently interpret the patterns of human actions in the designed situations.
With the deployment of game 1, the study collects rich empirical data on human decision-making, prediction capabilities, and so on. Analysing the collected data uncovers the behavioural patterns in competitive interactive situations of HHI. Hypotheses are formulated and rigorously
tested to evaluate the predictive abilities of observers, and the timing of transition phases within interactions. It is found that, in the designed dyadic alternative interaction situation, on one hand, the observers can successfully predict the target objects and the target
locations of the actors in the majority of the cases, and the leader observers have higher successful prediction rate of the target of the actors compared to the follower observers, as they have prior knowledge about the upcoming counteractions of the followers. Moreover, during
observation, the observers tend to start the prediction of target locations of the actors before the actors have actually touched the target objects. In addition, the observers start their own action roughly 1.58 seconds after the actors finish their actions. On the other hand,
the actors have 2.31 candidate target objects and 1.15 candidate target locations on average when planning. When they plan the target objects, they transit their eye fixations on the candidates 5.54 or 7.27 times on average based on different planning types (type Alpha actors start
the target location selection before the Touching event and tye Beta actors start it after the Touching event). As for fixation transitions of candidate target locations, the average numbers are 5.15 and 2.70 for type Alpha and type Beta, respectively.
Overall, this thesis contributes to the advancement of HRI research by introducing innovative experiment paradigms, conducting rigorous analyses, and providing valuable insights into human behaviour dynamics, through interactive HHI situation experiments. The findings pave the way
for future research aimed at further enhancing robot behaviors and fostering greater social acceptance in human-robot interactions.2024-06-2
LAA occlusion with the AMPLATZER devices - long term outcomes in a high-risk cohort
Langzeitergebnisse eines interventionellen Vorhofohrverschlusses durch einen Amplatzer-LAA-Okkluder in einem Hochrisikokollektiv
Der interventionelle Vorhofohrverschluss ist eine vorteilhafte Therapieoption bei Patienten mit Vorhofflimmern und Kontraindikationen für eine dauerhafte orale Antikoagulation. Die Effektivität der Methode zeigt sich im Nichtauftreten von Thromboembolien und Blutungen. Diese Studie ist eine monozentrische, retrospektive Kohortenstudie. Sie umfasst 212 Patienten, bei denen in der Zeit von 08‘2009 und 04‘2016 an der Universitätsmedizin Göttingen ein interventioneller Vorhofohrverschluss durchgeführt wurde. Alle Patienten hatten Vorhofflimmern und sowohl ein hohes Risiko für Thromboembolien als auch für Blutungen, der mittlere CHA2DS2-VASc-Score lag bei 5 ± 1,4 und der mittlere HAS-BLED-Score bei 3 ± 0,9. Ein telefonisches Follow-up wurde durchgeführt und die Endpunkte Schlaganfall, TIA, Thromboembolie, Device-assoziierte Komplikationen und Blutung erfasst. In einem Follow-up-Zeitraum von 1244,2 ± 756,7 Tagen und 674 Patientenjahren wurden 11 Schlaganfälle, drei TIAs, ein LAA-Thrombus, eine Device-assoziierte Komplikation und neun Blutungen beobachtet. Im Vergleich zum vorhergesagten Risiko mittels CHA2DS2-VASc-Score und HAS-BLED-Score konnte eine Risikoreduktion von 61 % für systemische Thromboembolien und eine Risikoreduktion von 74 % für Blutungen erreicht werden. Die Effektivität des interventionellen Vorhofohrverschlusses durch einen Amplatzer-LAA-Okkluder im längerfristigen Verlauf wurde demonstriert.LAA occlusion with the Amplatzer devices - long term outcomes in a high-risk cohort
LAA ooclusion is a favorable therapeutic option in patients with atrial fibrillation and contra-indications for oral anticoagulation therapy. The method proves its effectiveness by non-occurrence of thromboembolism and bleeding.
This study is a single-center, retrospective cohort study. It includes 212 patients, who underwent LAA occlusion between 08/2009 and 04/2016 at University Medicine Göttingen. All patients had atrial fibrillation and were at high risk for thromboembolism and bleeding, the mean CHA2DS2-VASc-Score was 5 ± 1,4 and the mean HAS-BLED-Score was 3 ± 0,9.
Follow-up was performed by phone call in 197 patients and focused on stroke, TIA, thromboembolism, device-related complications and bleeding. In a mean follow-up period of 1244,2 ± 756,7 days and 674 patient years we observed 11 strokes and three TIA, one LAA-thrombus, one device-related complication and nine bleedings. In comparison with the predicted risk for stroke and bleeding with the CHA2DS2-VASc-Score and the HAS-BLED-Score this study showed a risk reduction of 61 % for systemic thromboembolism and 74 % for bleeding. The effectiveness of the LAA-occlusion with the Amplatzer devices was demonstrated during a long-term follow-up period.2024-02-1
Match-paired study to assess influence of Kinematic versus Mechanical Alignment in Total Knee Replacement
Introduction: Match-paired study compares the early clinical and radiological outcomes after 2 weeks and 1-year between kinematic alignment total knee arthroplasty (KA TKA) and mechanical alignment total knee arthroplasty (MA TKA). Primary hypothesis were that KA TKAs patients have improved functional outcomes compared to MA TKAs patients? Secondary hypothesis was that there is difference between KA and MA patients.
Material and methods: A case-control study was carried out to compare the 2 weeks and 1-year clinical and radiographic outcomes between 24 consecutive KA-TKA patients and 24 matched MA-TKA patients. All patients had implantation with manual instruments and a cemented medial pivot TKA with excision of the PCL. All data were collected prospectively, and outcome scores were patient reported.
Results: KA patients had superior values in Forgotten Joint Score (FJS) at 2weeks and 1-year (KA 77 vs. MA 51) (p=0.05) follow-up. All other outcomes were not statistically significant but new Knee Society Score (KSS) (p=0.02), and in sport section of the Knee Osteoarthritis Outcome Score (KOOS) (p=0.01) after 1 year. Eleven out of 24 patients (46%) in KA group and 7/24 patients (29%) in MA group had limb alignment out of 180°±3°, whereas 17/24 (70%) of KA patients, and 14/24 (58%) of MA patients had orientation of tibial component with more than 3° of varus. No reoperation or revision occurred in either group.
Discussion/conclusion: The KA TKA design offers a good efficacy at early-term, with some 2 weeks and 1-year functional performance higher to the ones from MA TKA. Further research is needed to define if those early results will last over time.2024-02-2
Sleep complaints in depression and bipolar disorder course of therapy under intermittent theta burst stimulation or drug treatment
Es wurden insgesamt 73 Probanden in einer depressiven Phase über 5 Wochen auf
Veränderungen ihrer Schlafbeschwerden im Verlauf unterschiedlicher Therapien verglichen:
38 Probanden erhielten intermittierende Theta-Burst-Stimulation und 35 Probanden
erhielten konventionelle Antidepressiva. Zur Analyse wurde ein generalisiertes lineares
Modell verwendet. Die Studiengruppen unterschieden sich statistisch nicht signifikant in
Alter, Geschlecht und gesamten Bildungsjahren. Die Schlafbeschwerden gemessen durch die
Schlafitems des HDRS und die Schlafdauer verbesserten sich statistisch signifikant über die
Zeit, es konnte aber kein statistisch signifikanter Unterschied zwischen den
Behandlungsgruppen beobachtet werden. Probanden mit hoher initialer Insomnie erfuhren
eine statistisch signifikante Verbesserung in beiden Behandlungsgruppen. Die Verbesserung
der Schlafbeschwerden korrelierte statistisch signifikant mit einem generellen
Therapieansprechen und einer Verbesserung von ängstlichen Symptomen. Es konnte kein
Unterschied zwischen standardisiertem und personalisiertem Stimulationsprotokoll auf die
Schlafbeschwerden festgestellt werden. Diese Ergebnisse weisen auf eine Gleichwertigkeit
der Magnetstimulation im Vergleich zu Antidepressiva hin, um die Schlafbeschwerden bei
Depressionen zu lindern. Dabei stellt ein Vorteil der Magnetstimulation die geringeren
Nebenwirkungen dar. Weitere Studien mit Polysomnographie sind nötig um die Effektivität
der intermittierenden Theta-Burst-Stimulation in der Behandlung von Schlafbeschwerden
bei Depressionen weiter zu bestärken.A total of 73 test subjects in a depressive phase were compared over 5 weeks for changes in their sleep complaints over the course of different therapies: 38 subjects received intermittent theta burst stimulation and 35 subjects received conventional antidepressants. A generalised linear model was used for the analysis. The study groups did not differ statistically significantly in age, gender and total years of education. The sleep complaints measured by the sleep items of the HDRS and sleep duration improved statistically significantly over time, but no statistically significant difference was observed between the treatment groups. Subjects with high initial insomnia experienced experienced a statistically significant improvement in both treatment groups. The improvement of sleep complaints correlated statistically significantly with a general response to treatment and an improvement in anxiety symptoms. No difference was found between the standardised and personalised stimulation protocol on sleep complaints. These results indicate an equivalence of magnetic stimulation compared to antidepressants to alleviate sleep complaints in depression. One advantage of magnetic stimulation is that it has fewer side effects. Further studies with polysomnography are necessary to demonstrate the effectiveness of intermittent theta burst stimulation.2024-02-1
Dehydration behavior of hydrogels
Hydrogels, with their porous structures, steric networks, and high water content, which closely resemble living organisms, are attractive materials for numerous applications, including wound dressing, tissue engineering, and soft actuation. In reality, the dehydration of hydrogels always occurs, thereby modifying the characteristics of materials simultaneously. A thorough grasp of the physicochemical aspects of hydrogel dehydration can advance the use of hydrogels and also provide a new perspective on nature. The object of this research is to investigate the dehydration behavior of hydrogels and to fabricate functional materials via this path.
The reorganization of dynamic hydrogels during dehydration were systematically investigated, resulting in the xerogel hollow tubes with unique wall-knot structures via an anisotropic process. Unlike the typical isotropic contraction of hydrogels during dehydration, a fast reorganization of dynamic hydrogels facilitated the migration of polymers within the plane under the induced stress of dehydration. This led to the creation of hollow xerogel tubes with similar density and wall thickness or knots. Specifically, the conformal hydrogel-wall interfaces allowed the isotropic dehydration process to continue steadily. The universal nature of dynamic hydrogel reorganization during dehydration has been demonstrated. To a certain extent, this phenomenon is not influenced by the types of monomer or solvent utilized, dynamic bonds, and can even permeate through the interface between dynamic hydrogels. Combined with the conformality of hydrogel-wall interfaces, it provides a large scale curved surface with nanopatterns.
Then, inspired by the formation of heterogeneous structures of natural plants, xerogel fibers with heterogeneous structures were prepared after sequential uniaxial stretching and subsequent air drying. The observation reveals distinct properties of the inner part as core and outer layer as a sheath in one single sample. The outer layer was dense with stronger orientated microstructures, while the inner part was porous and uniform. By adapting Deborah number (De) to the air drying of hydrogels as interaction time, the formation of heterogeneous structures can be correlated with the divergent De, while tuning De values can trigger the transition from homogeneity to heterogeneity in xerogel fibers. Specifically, the turning point was around De = 1. Combining numerical modeling and experimental investigation, the mechanism behind the association between De and heterogeneity is water content-dependent glass transition. By quantitatively analyzing the results in DVS tests, this unique heterogeneous structure was demonstrated to be the key parameter in tuning the water transmission and the capacity of water holding. Herein, based on the physicochemical process in the modified dehydration process of dynamic hybrid hydrogels, we provide a new angle to understand the formation of heterogeneous structures in soft matter.
A new method was demonstrated to create a designable optical material system using cellulose nanocrystals (CNCs) that exhibit birefringence through alkaline periodate oxidation (PO-CNCs) and gold nanorods (GNRs) that exhibit surface plasmon resonance (SPR) by uniaxial stretching and hydrogels dehydration. The resulting system allows for adjustable structural colours. The GNRs films show obvious absorbance around 525 nm, while the intensity of absorbance is related to the concentration and the relative angle to the polarizer. The retardation induced by PO-CNCs can be used to manipulate the light intensity transmitted through the polarizer. In addition to direct changing the amounts of nanomaterials in the nanocomposite films, two further strategies can be used to design the structural colors and broaden the color space: stacking the PO-CNCs and GNRs films or changing the rotation angle of GNRs films. In comparison with the directly prepared PO-CNCs + GNRs hybrid films, these two strategies display high flexibility and modularization. For the first time, the PO-CNCs are applied as one important element in constructing optical materials with designable structural colors.
This thesis is a cumulative work including 3 publications. Two of them had already been published, and one was being prepared for submission. The background, the objective of the study, results and discussion of the three publications and the conclusions are presented in Section 1-4.2025-01-1
Sensory processing and learning in spiking neural networks
Organismen können sich in einer äußerst komplexen Umgebung mithilfe ihrer Sinne
zurechtfinden. Hierbei nutzen sie oft die Tatsache aus, dass hochdimensionale sensorische
Signale häufig aus vergleichsweise wenigen Informationen abgeleitet werden können,
beispielsweise aus der Position, Ausrichtung und anderen Eigenschaften eines Objekts in einer
visuellen Szene. Das Erlernen solch reduzierter Darstellungen sensorischer Daten vermindert
nicht nur drastisch die zu verarbeitende Informationsmenge, sondern kann auch zur
Entdeckung von Umgebungseigenschaften führen, die für höhere kognitive Prozesse
entscheidend sind.
Obwohl zahlreiche empirische Belege darauf hindeuten, dass solch erlernte Darstellungen für
die sensorische Verarbeitung entscheidend sind, bleibt offen, wie genau dieses Prinzip die
Darstellung von Informationen mit Nervenimpulsen in den verschiedenen Stufen der
sensorischen Verarbeitung im Gehirn beeinflusst. Aufeinander folgende Nervenimpulse
könnten aufgrund einer aktiven Unterdrückung vorhersehbarer Informationen in höheren
Hirnarealen weniger redundant sein, oder sie könnten aufgrund einer verstärkten Integration
vergangener Informationen sogar redundanter sein. Zur Untersuchung dieser Fragen in
neuronalen Daten haben wir ein Maß und ein Schätzverfahren entwickelt, um die
Vorhersagbarkeit der Impulsfolge einzelner Neuronen zu schätzen, das mit zeitlicher
Redundanz zusammenhängt, sowie einen Zeitrahmen für die Vorhersagbarkeit, der mit dem
Zeitrahmen der zeitlichen Integration zusammenhängt. In der visuellen Hirnrinde der Maus
haben wir festgestellt, dass die mittlere Vorhersagbarkeit entlang einer anatomischen Hirarchie
von Gehirnbereichen abnimmt, während der Zeitrahmen der Vorhersagbarkeit zunimmt. Diese
Ergebnisse legen eine Reduzierung der zeitlichen Redundanz entlang einer sensorischen
Verarbeitungshierarchie nahe, die mit einer längeren Integration vergangener Informationen in
der höheren sensorischen Verarbeitung einhergeht.
In theoretischer Arbeit adressieren wir außerdem, wie neuronale Netzwerke lernen können,
effiziente Darstellungen sensorischer Daten zu erzeugen. Das Lernen mit Nervenzellen, die
diskrete Impulse senden, birgt erhebliche Herausforderungen, da die diskrete Kommunikation
die Übertragung genauer Fehlersignale verhindert, die für das Lernen erforderlich sind. Zu
diesem Zweck führen wir das Konzept der dendritischen Fehlerberechnung ein, die eine lokale
Berechnung von Fehlersignalen an den Dendriten der Nervenzellen ermöglicht und somit die
Notwendigkeit ihrer Übertragung umgeht. Wir zeigen, dass die dendritische Fehlerberechnung
Schlüsselprobleme früherer Lernmodelle in neuronalen Netzwerken löst und diese Theorien zu
einem kohärenten Bild vereint. Weiterhin macht dieses Modell neue Vorhersagen auf
subzellulärer Ebene, wie etwa die Vorhersage eines engen Gleichgewichtes zwischen Erregung
und Inhibition auf der Ebene einzelner Dendritenäste oder die Vorhersage einer
Spannungsabhängigkeit synaptischer Plastizität.Organisms are capable of navigating an extremely complex environment with the help of their
senses. To do this, they exploit that high dimensional sensory inputs can often be predicted from
relatively sparse information, such as the location, orientation and other properties of an object
in a visual scene. Learning such sparse, predictive representations does not only drastically reduce
the amount of information that has to be processed, but may also lead to the discovery of features
of the environment that are key for higher cognitive processing.
Although ample empirical evidence indicates that sparse and predictive representations are
essential for sensory processing, it remains open how exactly this principle shapes neural spiking
representations across stages of sensory processing in the brain. Higher-level representations
might be less redundant in time because of an active suppression of predictable information, or
more redundant because of an enhanced integration of past information to represent more
complex spatio-temporal features. To investigate this in neural data, we developed a measure and
an estimation procedure to estimate predictability in single-neuron spiking, which is related to
temporal redundancy, as well as an information timescale, which is related to the timescale of
temporal integration. In mouse visual cortex, we find that median predictability decreases along
an anatomical hierarchy of brain areas, while the median information timescale increases. These
results suggest a reduction of temporal redundancy along a sensory processing hierarchy, which
coincides with a longer integration of past information in higher sensory areas.
In theoretical work, we further address how spiking neural networks can efficiently learn to
represent sparse and predictive representations of sensory inputs. Learning with spiking neurons
poses severe challenges because the temporally sparse communication with action potentials
prohibits the communication of high-fidelity error signals that are required for learning. To this
end, we introduce the concept of dendritic error computation, which enables a local
computation of error signals at neural dendrites, and thus circumvents the necessity to transmit
these signals. We show that dendritic error computation solves key issues of previous learning
schemes based on Hebbian-like plasticity in recurrent spiking networks, or distinct populations
of error neurons in hierarchical predictive coding. Strikingly, dendritic error computation does
not only unify these theories into a coherent picture of predictive coding in cortex, but also
makes novel predictions on the subcellular level, such as a tight excitation-inhibition balance on
the level of individual dendritic branches, or a voltage-dependence of synaptic plasticity. Finally,
we show that mismatch responses in cortex, which have been previously explained through
predictive processing with dedicated error neurons, can also arise in neural networks where
errors are computed in the dendrites. This provides a new perspective on the role of local
dendritic processing for sensory processing and learning in the spiking neural networks of the
brain.2025-02-1