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Background: There is extensive evidence that explicit memory, which involves conscious recall of encoded information, can be modulated by emotions; emotions may influence encoding, consolidation or retrieval of information. However, less is known about the modulatory effects of emotions on procedural processes like motor memory, which do not depend upon conscious recall and are instead demonstrated through changes in behaviour. Experiment 1: The goal of the first experiment was to examine the influence of emotions on motor learning. Four groups of subjects completed a motor learning task performing brisk isometric abductions with their thumb. While performing the motor task, the subjects heard emotional sounds varying in arousal and valence: (1) valence negative / arousal low (V-/A-), (2) valence negative / arousal high (V-/A+), (3) valence positive / arousal low (V+/A-), and (4) valence positive / arousal high (V+/A+). Descriptive analysis of the complete data set showed best performances for motor learning in the V-/A- condition, but the differences between the conditions did not reach significance. Results suggest that the interaction between valence and arousal may modulate motor encoding processes. Since limitations of the study cannot be ruled out, future studies with different emotional stimuli have to test the assumption that exposure to low arousing negative stimuli during encoding has a facilitating effect on short term motor memory. Experiment 2: The purpose of the second experiment was to investigate the effects of emotional interference on consolidation of sequential learning. In different sessions, 6 groups of subjects were initially trained on a serial reaction time task (SRTT). To modulate consolidation of the newly learned skill, subjects were exposed, after the training, to 1 of 3 (positive, negative or neutral) different classes of emotional stimuli which consisted of a set of emotional pictures combined with congruent emotional musical pieces or neutral sound. Emotional intervention for each subject group was done in 2 different time intervals (either directly after the training session, or 6 h later). After a 72 h post-training interval, each group was retested on the SRTT. Re-test performance was evaluated in terms of response times and accuracy during performance of the target sequence. Emotional intervention did not influence either response times or accuracy of re-testing SRTT task performance. However, explicit awareness of sequence knowledge was enhanced by arousing negative stimuli applied at 0 h after training. These findings suggest that consolidation of explicit aspects of procedural learning may be more responsive toward emotional interference than are implicit aspects. Consolidation of different domains of skill acquisition may be governed by different mechanisms. Since skill performance did not correlate with explicit awareness we suggest that implicit and explicit modes of SRTT performance are not complementary. Experiment 3: The aim of the third experiment was to analyze if the left hemisphere preferentially controls flexion responses towards positive stimuli, while the right hemisphere is specialized towards extensor responses to negative pictures. To this end, right-handed subjects had to pull or push a joystick subsequent to seeing a positive or a negative stimulus in their left or right hemifield. Flexion responses were faster for positive stimuli, while negative stimuli were associated with faster extensions responses. Overall, performance was fastest when emotional stimuli were presented to the left visual hemifield. This right hemisphere superiority was especially clear for negative stimuli, while reaction times towards positive pictures showed no hemispheric difference. We did not find any interaction between hemifield and response type. Neither was there a triple interaction between valence, hemifield and response type. In our experimental context the interaction between valence and hemifield seems to be stronger than the interaction between valence and motor behaviour. From these results we suppose that under certain conditions a hierarchy scaling of the asymmetry patterns prevails, which might mask any other existing asymmetries.
When More Is Better – Consumption Priming Decreases Responders’ Rejections in the Ultimatum Game
(2017)
During the past decades, economic theories of rational choice have been exposed to outcomes that were severe challenges to their claim of universal validity. For example, traditional theories cannot account for refusals to cooperate if cooperation would result in higher payoffs. A prominent illustration are responders’ rejections of positive but unequal payoffs in the Ultimatum Game. To accommodate this anomaly in a rational framework one needs to assume both a preference for higher payoffs and a preference for equal payoffs. The current set of studies shows that the relative weight of these preference components depends on external conditions and that consumption priming may decrease responders’ rejections of unequal payoffs. Specifically, we demonstrate that increasing the accessibility of consumption-related information accentuates the preference for higher payoffs. Furthermore, consumption priming increased responders’ reaction times for unequal payoffs which suggests an increased conflict between both preference components. While these results may also be integrated into existing social preference models, we try to identify some basic psychological processes underlying economic decision making. Going beyond the Ultimatum Game, we propose that a distinction between comparative and deductive evaluations may provide a more general framework to account for various anomalies in behavioral economics.
Utility is perhaps the most central concept in modern economic theorizing. However, the behaviorist reduction to Revealed Preference not only removed the psychological content of utility but experimental investigations also exposed numerous anomalies in this theory.
This program of research focused on the psychological processes by which utility judgments are generated. For this purpose, the standard assumption of a homogeneous concept is substituted by the Utilitarian Duality Hypothesis.
In particular, judgments concerning categorical utility (uCat) infer an object's category based on its attributes which may subsequently allow the transfer of evaluative information like feelings or attitudes. In contrast, comparative utility (uCom) depends on the distance to a reference value on a specific dimension of comparison. Importantly, dimensions of comparison are manifold and context dependent.
In a series of experiments, we show that the resulting Dual Utility Model is able to explain several known anomalies in a parsimonious fashion. Moreover, we identify central factors determining the relative weight assigned to both utility components.
Finally, we discuss the implications of the Utilitarian Duality for both, the experimental practice in economics as well as the consequences for economic theorizing. In sum, we propose that the Dual Utility Model can serve as an integrative framework for both the rational model and its anomalies.
The importance of proactive and timely prediction of critical events is steadily increasing, whether in the manufacturing industry or in private life. In the past, machines in the manufacturing industry were often maintained based on a regular schedule or threshold violations, which is no longer competitive as it causes unnecessary costs and downtime. In contrast, the predictions of critical events in everyday life are often much more concealed and hardly noticeable to the private individual, unless the critical event occurs. For instance, our electricity provider has to ensure that we, as end users, are always supplied with sufficient electricity, or our favorite streaming service has to guarantee that we can watch our favorite series without interruptions. For this purpose, they have to constantly analyze what the current situation is, how it will develop in the near future, and how they have to react in order to cope with future conditions without causing power outages or video stalling.
In order to analyze the performance of a system, monitoring mechanisms are often integrated to observe characteristics that describe the workload and the state of the system and its environment. Reactive systems typically employ thresholds, utility functions, or models to determine the current state of the system. However, such reactive systems cannot proactively estimate future events, but only as they occur. In the case of critical events, reactive determination of the current system state is futile, whereas a proactive system could have predicted this event in advance and enabled timely countermeasures. To achieve proactivity, the system requires estimates of future system states. Given the gap between design time and runtime, it is typically not possible to use expert knowledge to a priori model all situations a system might encounter at runtime. Therefore, prediction methods must be integrated into the system. Depending on the available monitoring data and the complexity of the prediction task, either time series forecasting in combination with thresholding or more sophisticated machine and deep learning models have to be trained.
Although numerous forecasting methods have been proposed in the literature, these methods have their advantages and disadvantages depending on the characteristics of the time series under consideration. Therefore, expert knowledge is required to decide which forecasting method to choose. However, since the time series observed at runtime cannot be known at design time, such expert knowledge cannot be implemented in the system. In addition to selecting an appropriate forecasting method, several time series preprocessing steps are required to achieve satisfactory forecasting accuracy. In the literature, this preprocessing is often done manually, which is not practical for autonomous computing systems, such as Self-Aware Computing Systems. Several approaches have also been presented in the literature for predicting critical events based on multivariate monitoring data using machine and deep learning. However, these approaches are typically highly domain-specific, such as financial failures, bearing failures, or product failures. Therefore, they require in-depth expert knowledge. For this reason, these approaches cannot be fully automated and are not transferable to other use cases. Thus, the literature lacks generalizable end-to-end workflows for modeling, detecting, and predicting failures that require only little expert knowledge.
To overcome these shortcomings, this thesis presents a system model for meta-self-aware prediction of critical events based on the LRA-M loop of Self-Aware Computing Systems. Building upon this system model, this thesis provides six further contributions to critical event prediction. While the first two contributions address critical event prediction based on univariate data via time series forecasting, the three subsequent contributions address critical event prediction for multivariate monitoring data using machine and deep learning algorithms. Finally, the last contribution addresses the update procedure of the system model. Specifically, the seven main contributions of this thesis can be summarized as follows:
First, we present a system model for meta self-aware prediction of critical events. To handle both univariate and multivariate monitoring data, it offers univariate time series forecasting for use cases where a single observed variable is representative of the state of the system, and machine learning algorithms combined with various preprocessing techniques for use cases where a large number of variables are observed to characterize the system’s state. However, the two different modeling alternatives are not disjoint, as univariate time series forecasts can also be included to estimate future monitoring data as additional input to the machine learning models. Finally, a feedback loop is incorporated to monitor the achieved prediction quality and trigger model updates.
We propose a novel hybrid time series forecasting method for univariate, seasonal time series, called Telescope. To this end, Telescope automatically preprocesses the time series, performs a kind of divide-and-conquer technique to split the time series into multiple components, and derives additional categorical information. It then forecasts the components and categorical information separately using a specific state-of-the-art method for each component. Finally, Telescope recombines the individual predictions. As Telescope performs both preprocessing and forecasting automatically, it represents a complete end-to-end approach to univariate seasonal time series forecasting. Experimental results show that Telescope achieves enhanced forecast accuracy, more reliable forecasts, and a substantial speedup. Furthermore, we apply Telescope to the scenario of predicting critical events for virtual machine auto-scaling. Here, results show that Telescope considerably reduces the average response time and significantly reduces the number of service level objective violations.
For the automatic selection of a suitable forecasting method, we introduce two frameworks for recommending forecasting methods. The first framework extracts various time series characteristics to learn the relationship between them and forecast accuracy. In contrast, the other framework divides the historical observations into internal training and validation parts to estimate the most appropriate forecasting method. Moreover, this framework also includes time series preprocessing steps. Comparisons between the proposed forecasting method recommendation frameworks and the individual state-of-the-art forecasting methods and the state-of-the-art forecasting method recommendation approach show that the proposed frameworks considerably improve the forecast accuracy.
With regard to multivariate monitoring data, we first present an end-to-end workflow to detect critical events in technical systems in the form of anomalous machine states. The end-to-end design includes raw data processing, phase segmentation, data resampling, feature extraction, and machine tool anomaly detection. In addition, the workflow does not rely on profound domain knowledge or specific monitoring variables, but merely assumes standard machine monitoring data. We evaluate the end-to-end workflow using data from a real CNC machine. The results indicate that conventional frequency analysis does not detect the critical machine conditions well, while our workflow detects the critical events very well with an F1-score of almost 91%.
To predict critical events rather than merely detecting them, we compare different modeling alternatives for critical event prediction in the use case of time-to-failure prediction of hard disk drives. Given that failure records are typically significantly less frequent than instances representing the normal state, we employ different oversampling strategies. Next, we compare the prediction quality of binary class modeling with downscaled multi-class modeling. Furthermore, we integrate univariate time series forecasting into the feature generation process to estimate future monitoring data. Finally, we model the time-to-failure using not only classification models but also regression models. The results suggest that multi-class modeling provides the overall best prediction quality with respect to practical requirements. In addition, we prove that forecasting the features of the prediction model significantly improves the critical event prediction quality.
We propose an end-to-end workflow for predicting critical events of industrial machines. Again, this approach does not rely on expert knowledge except for the definition of monitoring data, and therefore represents a generalizable workflow for predicting critical events of industrial machines. The workflow includes feature extraction, feature handling, target class mapping, and model learning with integrated hyperparameter tuning via a grid-search technique. Drawing on the result of the previous contribution, the workflow models the time-to-failure prediction in terms of multiple classes, where we compare different labeling strategies for multi-class classification. The evaluation using real-world production data of an industrial press demonstrates that the workflow is capable of predicting six different time-to-failure windows with a macro F1-score of 90%. When scaling the time-to-failure classes down to a binary prediction of critical events, the F1-score increases to above 98%.
Finally, we present four update triggers to assess when critical event prediction models should be re-trained during on-line application. Such re-training is required, for instance, due to concept drift. The update triggers introduced in this thesis take into account the elapsed time since the last update, the prediction quality achieved on the current test data, and the prediction quality achieved on the preceding test data. We compare the different update strategies with each other and with the static baseline model. The results demonstrate the necessity of model updates during on-line application and suggest that the update triggers that consider both the prediction quality of the current and preceding test data achieve the best trade-off between prediction quality and number of updates required.
We are convinced that the contributions of this thesis constitute significant impulses for the academic research community as well as for practitioners. First of all, to the best of our knowledge, we are the first to propose a fully automated, end-to-end, hybrid, component-based forecasting method for seasonal time series that also includes time series preprocessing. Due to the combination of reliably high forecast accuracy and reliably low time-to-result, it offers many new opportunities in applications requiring accurate forecasts within a fixed time period in order to take timely countermeasures. In addition, the promising results of the forecasting method recommendation systems provide new opportunities to enhance forecasting performance for all types of time series, not just seasonal ones. Furthermore, we are the first to expose the deficiencies of the prior state-of-the-art forecasting method recommendation system.
Concerning the contributions to critical event prediction based on multivariate monitoring data, we have already collaborated closely with industrial partners, which supports the practical relevance of the contributions of this thesis. The automated end-to-end design of the proposed workflows that do not demand profound domain or expert knowledge represents a milestone in bridging the gap between academic theory and industrial application. Finally, the workflow for predicting critical events in industrial machines is currently being operationalized in a real production system, underscoring the practical impact of this thesis.
Zyberaj, Jetmir ; Seibel, Sebastian ; Schowalter, Annika F. ; Pötz, Lennart ; Richter-Killenberg, Stefanie ; Volmer, Judith
The Coronavirus disease 2019 (COVID-19) has not only had negative effects on employees' health, but also on their prospects to gain and maintain employment. Using a longitudinal research design with two measurement points, we investigated the ramifications of various psychological and organizational resources on employees' careers during the COVID-19 pandemic. Specifically, in a sample of German employees (N = 305), we investigated the role of psychological capital (PsyCap) for four career-related outcomes: career satisfaction, career engagement, coping with changes in career due to COVID-19, and career-related COVID-19 worries. We also employed leader–member exchange (LMX) as a moderator and career adaptability as a mediating variable in these relationships. Results from path analyses revealed a positive association between PsyCap and career satisfaction and career coping. Furthermore, PsyCap was indirectly related to career engagement through career adaptability. However, moderation analysis showed no moderating role of LMX on the link between PsyCap and career adaptability. Our study contributes to the systematic research concerning the role of psychological and organizational resources for employees' careers and well-being, especially for crisis contexts.
Assessing protein biomarkers to detect lethal acute traumatic brain injuries in cerebrospinal fluid
(2021)
Zwirner, Johann ; Bohnert, Simone ; Franke, Heike ; Garland, Jack ; Hammer, Niels ; Möbius, Dustin ; Tse, Rexson ; Ondruschka, Benjamin
Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R\(^2\) = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.
Zwirner, Johann ; Anders, Sven ; Bohnert, Simone ; Burkhardt, Ralph ; Da Broi, Ugo ; Hammer, Niels ; Pohlers, Dirk ; Tse, Rexson ; Ondruschka, Benjamin
A single, specific, sensitive biochemical biomarker that can reliably diagnose a traumatic brain injury (TBI) has not yet been found, but combining different biomarkers would be the most promising approach in clinical and postmortem settings. In addition, identifying new biomarkers and developing laboratory tests can be time-consuming and economically challenging. As such, it would be efficient to use established clinical diagnostic assays for postmortem biochemistry. In this study, postmortem cerebrospinal fluid samples from 45 lethal TBI cases and 47 controls were analyzed using commercially available blood-validated assays for creatine kinase (CK) activity and its heart-type isoenzyme (CK–MB). TBI cases with a survival time of up to two hours showed an increase in both CK and CK–MB with moderate (CK–MB: AUC = 0.788, p < 0.001) to high (CK: AUC = 0.811, p < 0.001) diagnostic accuracy. This reflected the excessive increase of the brain-type CK isoenzyme (CK–BB) following a TBI. The results provide evidence that CK immunoassays can be used as an adjunct quantitative test aid in diagnosing acute TBI-related fatalities.
Zwink, Nadine ; Jenetzky, Ekkehart ; Schmiedeke, Eberhard ; Schmidt, Dominik ; Märzheuser, Schmidt ; Grasshoff-Derr, Sabine ; Holland-Cunz, Stefan ; Weih, Sandra ; Hosie, Stuart ; Reifferscheid, Peter ; Ameis, Helen ; Kujath, Christina ; Rissmann, Anke ; Obermayr, Florian ; Schwarzer, Nicole ; Bartels, Enrika ; Reutter, Heiko ; Brenner, Hermann
Background: The use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
Methods: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births.
Results: In total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9-12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2-19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6-12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6-12.7) for singletons and 4.9 (2.4-10.1) for multiple births. Conclusions: There is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.
Fluorescence microscopy is a form of light microscopy that has developed during the 20th century and is nowadays a standard tool in Molecular and Cell biology for studying the structure and function of biological molecules. High-resolution fluorescence microscopy techniques, such as dSTORM (direct Stochastic Optical Reconstruction Microscopy) allow the visualization of cellular structures at the nanometre scale (10−9 m). This has already made it possible to decipher the composition and function of various biopolymers, such as proteins, lipids and nucleic acids, up to the three-dimensional (3D) structure of entire organelles. In practice, however, it has been shown that these imaging methods and their further developments still face great challenges in order to achieve an effective resolution below ∼ 10 nm. This is mainly due to the nature of labelling biomolecules. For the detection of molecular structures, immunostaining is often performed as a standard method. Antibodies to which fluorescent molecules are coupled, recognize and bind specifcally and with high affnity to the molecular section of the target structure, also called epitope or antigen. The fluorescent molecules serve as reporter molecules which are imaged with the use of a fluorescence microscope. However, the size of these labels with a length of about 10-15 nm in the case of immunoglobulin G (IgG) antibodies, cause a detection of the fluorescent molecules shifted to the real position of the studied antigen. In dense regions where epitopes are located close to each other, steric hindrance between antibodies can also occur and leads to an insuffcient label density. Together with the shifted detection of fluorescent molecules, these factors can limit the achievable resolution of a microscopy technique. Expansion microscopy (ExM) is a recently developed technique that achieves a resolution improvement by physical expansion of an investigated object. Therefore, biological samples such as cultured cells, tissue sections, whole organs or isolated organelles are chemically anchored into a swellable polymer. By absorbing water, this so-called superabsorber increases its own volume and pulls the covalently bound biomolecules isotropically apart. Routinely, this method achieves a magnifcation of the sample by about four times its volume. But protocol variants have already been developed that result in higher expansion factors of up to 50-fold. Since the ExM technique includes in the frst instance only the sample treatment for anchoring and magnifcation of the sample, it can be combined with various standard methods of fluorescence microscopy. In theory, the resolution of the used imaging technique improves linearly with the expansion factor of the ExM treated sample. However, an insuffcient label density and the size of the antibodies can here again impair the effective achievable resolution. The combination of ExM with high-resolution fluorescence microscopy methods represents a promising strategy to increase the resolution of light microscopy. In this thesis, I will present several ExM variants I developed which show the combination of ExM with confocal microscopy, SIM (Structured Illumination Microscopy), STED (STimulated Emission Depletion) and dSTORM. I optimized existing ExM protocols and developed different expansion strategies, which allow the combination with the respective imaging technique. Thereby, I gained new structural insights of isolated centrioles from the green algae Chlamydomonas reinhardtii by combining ExM with STED and confocal microscopy. In another project, I combined 3D-SIM imaging with ExM and investigated the molecular structure of the so-called synaptonemal complex. This structure is formed during meiosis in eukaryotic cells and contributes to the exchange of genetic material between homologous chromosomes. Especially in combination with dSTORM, the ExM method showed its high potential to overcome the limitations of modern fluorescence microscopy techniques. In this project, I expanded microtubules in mammalian cells, a polymer of the cytoskeleton as well as isolated centrioles from C. reinhardtii. By labelling after expansion of the samples, I was able to signifcantly reduce the linkage error of the label and achieve an improved label density. In future, these advantages together with the single molecule sensitivity and high resolution obtained by the dSTORM method could pave the way for achieving molecular resolution in fluorescence microscopy
Zvirblis, G. S. ; Gorboulev, Valentin G. ; Rubtsov, P. M. ; Chernov, B. K. ; Golova, Yu. B. ; Pozmogova, G. E. ; Skryabin, K. G. ; Bayev, A. A.
Results are presented of cloning cDNA of procine growth hormone, analysis of its primary structure, and creation of a construction capable of expression of this cDNA in Esqheriahia coti cells. It is shown that in the population of mRNA coding porcine growth hormone, heterogeneity is noted which is manifested not only at the level of the nucleotide sequence, but also is reflected in the amino acid sequence of the mature hormone.
Zusan, Andreas ; Gieseking, Björn ; Zerson, Mario ; Dyakonov, Vladimir ; Magerle, Robert ; Deibel, Carsten
Microstructural changes and the understanding of their effect on photocurrent generation are key aspects for improving the efficiency of organic photovoltaic devices. We analyze the impact of a systematically increased amount of the solvent additive diiodooctane (DIO) on the morphology of PBDTTT-C:PC71BM blends and related changes in free carrier formation and recombination by combining surface imaging, photophysical and charge extraction techniques. We identify agglomerates visible in AFM images of the 0% DIO blend as PC71BM domains embedded in an intermixed matrix phase. With the addition of DIO, a decrease in the size of fullerene domains along with a demixing of the matrix phase appears for 0.6% and 1% DIO. Surprisingly, transient absorption spectroscopy reveals an efficient photogeneration already for the smallest amount of DIO, although the largest efficiency is found for 3% DIO. It is ascribed to a fine-tuning of the blend morphology in terms of the formation of interpenetrating donor and acceptor phases minimizing geminate and nongeminate recombination as indicated by charge extraction experiments. An increase in the DIO content to 10% adversely affects the photovoltaic performance, most probably due to an inefficient free carrier formation and trapping in a less interconnected donor-acceptor network.
Organic solar cells have great potential to become a low-cost and clean alternative to conventional photovoltaic technologies based on the inorganic bulk material silicon. As a highly promising concept in the field of organic photovoltaics, bulk heterojunction (BHJ) solar cells consist of a mixture of an electron donating and an electron withdrawing component. Their degree of intermixing crucially affects the generation of photocurrent. In this work, the effect of an altered blend morphology on polaron pair dissociation, charge carrier transport, and nongeminate recombination is analyzed by the charge extraction techniques time delayed collection field (TDCF) and open circuit corrected transient charge extraction (OTRACE). Different comparative studies cover a broad range of material systems, including polymer and small-molecule donors in combination with different fullerene acceptors. The field dependence of polaron pair dissociation is analyzed in blends based on the polymer pBTTT-C16, allowing a systematic tuning of the blend morphology by varying the acceptor type and fraction. The effect of both excess photon energy and intercalated phases are minor compared to the influence of excess fullerene, which reduces the field dependence of photogeneration. The study demonstrates that the presence of neat fullerene domains is the major driving force for efficient polaron pair dissociation that is linked to the delocalization of charge carriers. Furthermore, the influence of the processing additive diiodooctane (DIO) is analyzed using the photovoltaic blends PBDTTT-C:PC71BM and PTB7:PC71BM. The study reveals amulti-tiered alteration of the blend morphology of PBDTTT-C based blends upon a systematic increase of the amount of DIO. Domains on the hundred nanometers length scale in the DIO-free blend are identified as neat fullerene agglomerates embedded in an intermixed matrix. With the addition of the additive, 0.6% and 1% DIO already substantially reduces the size of these domains until reaching the optimum 3% DIO mixture, where a 7.1% power conversion efficiency is obtained. It is brought into connection with the formation of interpenetrating polymer and fullerene phases. Similar to PBDTTT-C, the morphology of DIO-free PTB7:PC71BM blends is characterized by large fullerene domains being decreased in size upon the addition of 3% DIO. OTRACE measurements reveal a reduced Langevin-type, super-second order recombination in both blends. It is demonstrated that the deviation from bimolecular recombination kinetics cannot be fully attributed to the carrier density dependence of the mobility but is rather related to trapping in segregated PC71BM domains. Finally, with regard to small-molecule donors, a higher yield of photogeneration and balanced transport properties are identified as the dominant factors enhancing the efficiency of vacuum deposited MD376:C60 relative to its solution processed counterpart MD376:PC61BM. The finding is explained by a higher degree of dimerization of the merocyanine dye MD376 and a stronger donor-acceptor interaction at the interface in the case of the vacuum deposited blend.
Government funding of research beyond biomedicine: challenges and opportunities for neuroethology
(2022)
Curiosity-driven research is fundamental for neuroethology and depends crucially on governmental funding. Here, we highlight similarities and differences in funding of curiosity-driven research across countries by comparing two major funding agencies—the National Science Foundation (NSF) in the United States and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). We interviewed representatives from each of the two agencies, focusing on general funding trends, levels of young investigator support, career-life balance, and international collaborations. While our analysis revealed a negative trend in NSF funding of biological research, including curiosity-driven research, German researchers in these areas have benefited from a robust positive trend in DFG funding. The main reason for the decrease in curiosity-driven research in the US is that the NSF has only partially been able to compensate for the funding gap resulting from the National Institutes of Health restricting their support to biomedical research using select model organisms. Notwithstanding some differences in funding programs, particularly those relevant for scientists in the postdoctoral phase, both the NSF and DFG clearly support curiosity-driven research.
Zullo, Alberto ; Fleckenstein, Johannes ; Schleip, Robert ; Hoppe, Kerstin ; Wearing, Scott ; Klingler, Werner
Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.
Zukher, Inna ; Novikova, Maria ; Tikhonov, Anton ; Nesterchuk, Mikhail V. ; Osterman, Ilya A. ; Djordjevic, Marko ; Sergiev, Petr V. ; Sharma, Cynthia M. ; Severinov, Konstantin
Microcin C (McC) is a peptide-nucleotide antibiotic produced by Escherichia coli cells harboring a plasmid-borne operon mccABCDE. The heptapeptide MccA is converted into McC by adenylation catalyzed by the MccB enzyme. Since MccA is a substrate for MccB, a mechanism that regulates the MccA/MccB ratio likely exists. Here, we show that transcription from a promoter located upstream of mccA directs the synthesis of two transcripts: a short highly abundant transcript containing the mccA ORF and a longer minor transcript containing mccA and downstream ORFs. The short transcript is generated when RNA polymerase terminates transcription at an intrinsic terminator located in the intergenic region between the mccA and mccB genes. The function of this terminator is strongly attenuated by upstream mcc sequences. Attenuation is relieved and transcription termination is induced when ribosome binds to the mccA ORF. Ribosome binding also makes the mccA RNA exceptionally stable. Together, these two effects-ribosome induced transcription termination and stabilization of the message-account for very high abundance of the mccA transcript that is essential for McC production. The general scheme appears to be evolutionary conserved as ribosome-induced transcription termination also occurs in a homologous operon from Helicobacter pylori.
Bacterial mastitis is caused by invasion of the udder, bacterial multiplication and induction of
inflammatory responses in the bovine mammary gland. Disease severity and the cause of disease are
influenced by environmental factors, the cow’s immune response as well as bacterial traits. Escherichia coli (E. coli) is one of the main causes of acute bovine mastitis, but although pathogenic E. coli strains can be classified into different pathotypes, E. coli causing mastitis cannot unambiguously be distinguished from commensal E. coli nor has a common set of virulence factors
been described for mastitis isolates. This project focussed on the characterization of virulence-
associated traits of E. coli mastitis isolates in comprehensive analyses under conditions either
mimicking initial pathogenesis or conditions that E. coli mastitis isolates should encounter while entering the udder. Virulence-associated traits as well as fitness traits of selected bovine mastitis or faecal E. coli strains were identified and analyzed in comparative phenotypic assays. Raw milk whey was introduced to
test bacterial fitness in native mammary secretion known to confer antimicrobial effects.
Accordingly, E. coli isolates from bovine faeces represented a heterogeneous group of which some
isolates showed reduced ability to survive in milk whey whereas others phenotypically resembled
mastitis isolates that represented a homogeneous group in that they showed similar survival and
growth characteristics in milk whey. In contrast, mastitis isolates did not exhibit such a uniform phenotype when challenged with iron shortage, lactose as sole carbon source and lingual
antimicrobial peptide (LAP) as a main defensin of milk. Reduced bacterial fitness could be related to LAP suggesting that bacterial adaptation to an intramammary lifestyle requires resistance to host
defensins present in mammary secretions, at least LAP.
E. coli strain 1303 and ECC-1470 lack particular virulence genes associated to mastitis isolates. To find out whether differences in gene expression may contribute to the ability of E. coli variants to cause mastitis, the transcriptome of E. coli model mastitis isolates 1303 and ECC-1470 were analyzed to
identify candidate genes involved in bacterium-host interaction, fitness or even pathogenicity during bovine mastitis.
DNA microarray analysis was employed to assess the transcriptional response of E. coli 1303 and
ECC-1470 upon cocultivation with MAC-T immortalized bovine mammary gland epithelial cells to
identify candidate genes involved in bacterium-host interaction. Additionally, the cell adhesion and invasion ability of E. coli strain 1303 and ECC-1470 was investigated. The transcriptonal response to the presence of host cells rather suggested competition for nutrients and oxygen between E. coli and MAC-T cells than marked signs of adhesion and invasion. Accordingly, mostly fitness traits that may also contribute to efficient colonization of the E. coli primary habitat, the gut, have been utilized by the mastitis isolates under these conditions. In this study, RNA-Seq was employed to assess the bacterial transcriptional response to milk whey.
According to our transcriptome data, the lack of positively deregulated and also of true virulence-associated determinants in both of the mastitis isolates indicated that E. coli might have adapted by other means to the udder (or at least mammary secretion) as an inflammatory site. We identified traits that promote bacterial growth and survival in milk whey. The ability to utilize citrate promotes fitness and survival of E. coli that are thriving in mammary secretions. According to our results, lactoferrin has only weak impact on E. coli in mammary secretions. At the same time bacterial determinants involved in iron assimilation were negatively regulated, suggesting that, at least during the first hours, iron assimilation is not a challenge to E. coli colonizing the mammary gland. It has been hypothesized that cellular iron stores cause temporary independency to extracellular accessible iron. According to our transcriptome data, this hypothesis was supported and places iron uptake
systems beyond the speculative importance that has been suggested before, at least during early
phases of infection. It has also been shown that the ability to resist extracytoplasmic stress, by oxidative conditions as well as host defensins, is of substantial importance for bacterial survival in mammary secretions.
In summary, the presented thesis addresses important aspects of host-pathogen interaction and
bacterial conversion to hostile conditions during colonization of the mastitis inflammatory site, the mammary gland.
Neuronal representation and processing of chemosensory communication signals in the ant brain
(2008)
Ants heavily rely on olfaction for communication and orientation and ant societies are characterized by caste- and sex-specific division of labor. Olfaction plays a key role in mediating caste-specific behaviours. I investigated whether caste- and sex-specific differences in odor driven behavior are reflected in specific differences and/or adaptations in the ant olfactory system. In particular, I asked the question whether in the carpenter ant, Camponotus floridanus, the olfactory pathway exhibits structural and/or functional adaptations to processing of pheromonal and general odors. To analyze neuroanatomical specializations, the central olfactory pathway in the brain of large (major) workers, small (minor) workers, virgin queens, and males of the carpenter ant C. floridanus was investigated using fluorescent tracing, immunocytochemistry, confocal microscopy and 3D-analyzes. For physiological analyzes of processing of pheromonal and non-pheromonal odors in the first odor processing neuropil , the antennal lobe (AL), calcium imaging of olfactory projection neurons (PNs) was applied. Although different in total glomerular volumes, the numbers of olfactory glomeruli in the ALs were similar across the female worker caste and in virgin queens. Here the AL contains up to ~460 olfactory glomeruli organized in 7 distinct clusters innervated via 7 antennal sensory tracts. The AL is divided into two hemispheres regarding innervations of glomeruli by PNs with axons leaving via a dual output pathway. This pathway consists of the medial (m) and lateral (l) antenno-cerebral tract (ACT) and connects the AL with the higher integration areas in the mushroom bodies (MB) and the lateral horn (LH). M- and l-ACT PNs differ in their target areas in the MB calyx and the LH. Three additional ACTs (mediolateral - ml) project to the lateral protocerebrum only. Males had ~45% fewer glomeruli compared to females and one of the seven sensory tracts was absent. Despite a substantially smaller number of glomeruli, males possess a dual PN output pathway to the MBs. In contrast to females, however, only a small number of glomeruli were innervated by projection neurons of the m-ACT. Whereas all glomeruli in males were densely innervated by serotonergic processes, glomeruli innervated by sensory tract six lacked serotonergic innervations in the female castes. It appears that differences in general glomerular organization are subtle among the female castes, but sex-specific differences in the number, connectivity and neuromodulatory innervations of glomeruli are substantial and likely to promote differences in olfactory behavior. Calcium imaging experiments to monitor pheromonal and non-pheromonal processing in the ant AL revealed that odor responses were reproducible and comparable across individuals. Calcium responses to both odor groups were very sensitive (10-11 dilution), and patterns from both groups were partly overlapping indicating that processing of both odor classes is not spatially segregated within the AL. Intensity response patterns to the pheromone components tested (trail pheromone: nerolic acid; alarm pheromone: n-undecane), in most cases, remained invariant over a wide range of intensities (7-8 log units), whereas patterns in response to general odors (heptanal, octanol) varied across intensities. Durations of calcium responses to stimulation with the trail pheromone component nerolic acid increased with increasing odor concentration indicating that odor quality is maintained by a stable pattern (concentration invariance) and intensity is mainly encoded in the response durations of calcium activities. For n-undecane and both general odors increasing response dynamics were only monitored in very few cases. In summary, this is the first detailed structure-function analyses within the ant’s central olfactory system. The results contribute to a better understanding of important aspects of odor processing and olfactory adaptations in an insect’s central olfactory system. Furthermore, this study serves as an excellent basis for future anatomical and/or physiological experiments.
Zoungrana, Benewinde Jean-Bosco ; Conrad, Christopher ; Amekudzi, Leonard K. ; Thiel, Michael ; Dapola Da, Evariste ; Forkuor, Gerald ; Löw, Fabian
Accurate quantification of land use/cover change (LULCC) is important for efficient environmental management, especially in regions that are extremely affected by climate variability and continuous population growth such as West Africa. In this context, accurate LULC classification and statistically sound change area estimates are essential for a better understanding of LULCC processes. This study aimed at comparing mono-temporal and multi-temporal LULC classifications as well as their combination with ancillary data and to determine LULCC across the heterogeneous landscape of southwest Burkina Faso using accurate classification results. Landsat data (1999, 2006 and 2011) and ancillary data served as input features for the random forest classifier algorithm. Five LULC classes were identified: woodland, mixed vegetation, bare surface, water and agricultural area. A reference database was established using different sources including high-resolution images, aerial photo and field data. LULCC and LULC classification accuracies, area and area uncertainty were computed based on the method of adjusted error matrices. The results revealed that multi-temporal classification significantly outperformed those solely based on mono-temporal data in the study area. However, combining mono-temporal imagery and ancillary data for LULC classification had the same accuracy level as multi-temporal classification which is an indication that this combination is an efficient alternative to multi-temporal classification in the study region, where cloud free images are rare. The LULCC map obtained had an overall accuracy of 92%. Natural vegetation loss was estimated to be 17.9% ± 2.5% between 1999 and 2011. The study area experienced an increase in agricultural area and bare surface at the expense of woodland and mixed vegetation, which attests to the ongoing deforestation. These results can serve as means of regional and global land cover products validation, as they provide a new validated data set with uncertainty estimates in heterogeneous ecosystems prone to classification errors.
Based on the strand‐like coordination polymer (CP) type \(^{1}\)\(_{∞}\)[Ln(BSB)\(_{3}\)(py)\(_{2}\)], [BSB]−=bis‐salicylatoborate anion, mixed Eu/Tb‐containing compounds of the constitution \(^{1}\)\(_{∞}\)[Eu\(_{x}\)Tb\(_{1-x}\)(BSB)\(_{3}\)(py)\(_{2}\)] were synthesised ionothermally for a phase width of (x=0.25–0.75) and characterized regarding structure and optical properties. Previously, known only for other lanthanides, the mixed 1D−Eu/Tb‐CPs show excellent options for statistic replacement of the Ln‐cations during synthesis yielding solid solutions. The products are highly luminescent, with the chromaticity being a direct function of the amount of the respective Ln‐ions. Corresponding to an overall addition of emission intensities, the green Tb\(^{3+}\) emission and the red Eu\(^{3+}\) emission allow for a chromaticity control that also includes yellow emission. Control of the luminescence colour renders them suitable examples of the versatility of statistic replacement of metal ions in coordination chemistry. In addition, crystallization of [EMIm]\(_{2}\)[YCl\(_{5}\)(py)] illuminates possible other products of the ionothermal reactions of [EMIm][BSB] with LnCl\(_{3}\) constituted by components not being part of the main CPs.