To cope with environmental changes, humans need to adjust their cognitive control states to meet different challenges. Two important cognitive control states are cognitive persistence and cognitive... Show moreTo cope with environmental changes, humans need to adjust their cognitive control states to meet different challenges. Two important cognitive control states are cognitive persistence and cognitive flexibility. Persistence is a state of maintaining stable attention, while flexibility is a state where attention can switch freely. These two states are antagonistic to each other; one cannot switch attention flexibly while being focused, and one cannot focus on a single stimulus while switching attention flexibly. Our understanding of the neural mechanisms underlying these cognitive control states is still limited. Therefore, in this dissertation, we used two brain science research techniques, EEG and fMRI, to study brain activities associated with these two states. To induce these states, the dissertation employed two creative thinking tasks, namely convergent thinking and divergent thinking, and two meditation techniques, focused attention meditation and open monitoring meditation. The results discuss EEG and fMRI indicators related to these states, providing preliminary evidence for research in this field. Show less
This thesis focused on the exploration of monolayer graphene as a membrane in direct methanol fuel cell (DMFC) applications, with improvements achieved through plasma exposure or damage- free... Show moreThis thesis focused on the exploration of monolayer graphene as a membrane in direct methanol fuel cell (DMFC) applications, with improvements achieved through plasma exposure or damage- free chemical functionalization. The advancements in low-dimensional materials (LDMs) have unveiled a new era where artificial membranes can regulate ion transport with atomic precision.The trade-off between selectivity and conductivity, which has impeded the development of proton exchange membranes, has been overcome through monolayer graphene, making it applicable in large-scale devices such as DMFCs. This work has the potential to solve many challenges faced by devices requiring proton exchange membranes, extending beyond fuel cells. Show less
The study focuses on how to establish prohibited airspace over conflict zones.This study endeavors to answer the following research questions:1) What are the conditions, including legal... Show moreThe study focuses on how to establish prohibited airspace over conflict zones.This study endeavors to answer the following research questions:1) What are the conditions, including legal requirements, for establishing prohibited airspace?2) Who has jurisdiction to establish prohibited airspace?3) How can the status quo be changed with respect to prohibited airspace to enhance aviation security?The establishment of prohibited airspace concerns on the one hand, the principle of air sovereignty, agreed by governments as recognized in Article 1 Chicago Convention, and on the other hand, the object of agreeing on this principle to “develop international civil aviation in a safe and orderly manner”.Threads running through the chapters are the themes of sovereignty, jurisdiction, and territory. Show less
This research analyses to what extent China is achieving decent work based on a case study of decent working time. The word ‘achieving’ underlines that China is still in the process of securing... Show moreThis research analyses to what extent China is achieving decent work based on a case study of decent working time. The word ‘achieving’ underlines that China is still in the process of securing this aim. This research builds on a mixed methodology of case study, historical analysis, content analysis, structured critical analysis, and comparative law. The findings show that the development goal of decent work has not been achieved in China, but there are some significant developments. Particularly, many labour standards with regard to workers’ health and safety have markedly been intensified and increased, as have the making and enforcement of Chinese labour laws, which both are signals that China has created an environment receptive to further reform and development on its path to achieving decent work. Show less
B and T cell receptor (immune) repertoires can represent an individual’s immune history. While current repertoire analysis methods aim to discriminate between health and disease states, they are... Show moreB and T cell receptor (immune) repertoires can represent an individual’s immune history. While current repertoire analysis methods aim to discriminate between health and disease states, they are typically based on only a limited number of parameters. Here, we introduce immuneREF: a quantitative multidimensional measure of adaptive immune repertoire (and transcriptome) similarity that allows interpretation of immune repertoire variation by relying on both repertoire features and cross-referencing of simulated and experimental datasets. To quantify immune repertoire similarity landscapes across health and disease, we applied immuneREF to >2,400 datasets from individuals with varying immune states (healthy, [autoimmune] disease, and infection). We discovered, in contrast to the current paradigm, that blood-derived immune repertoires of healthy and diseased individuals are highly similar for certain immune states, suggesting that repertoire changes to immune perturbations are less pronounced than previously thought. In conclusion, immuneREF enables the population-wide study of adaptive immune response similarity across immune states. Show less
Colzato, L.S.; Beste, C.; Zhang, W.; Hommel B. 2022
Biomedical and clinical questions increasingly deal with biomass-restricted samples. To address these questions with a metabolomics approach, the development of new microscale analytical techniques... Show moreBiomedical and clinical questions increasingly deal with biomass-restricted samples. To address these questions with a metabolomics approach, the development of new microscale analytical techniques and workflows is needed. Over the past few years, significant efforts have been made to improve the overall sensitivity of MSbased metabolomics workflows to enable the analysis of biological samples that are low in metabolite concentration or biomass. In this paper, factors that are crucial for the performance of biomass-restricted metabolomics studies are discussed, including sampling and sample preparation methods, separation techniques and ionization sources. Overviews of MS-based miniaturized metabolomics studies reported over the past five years are given in tables, with information provided on sample type, sample preparation volume, injection volume, separation techniques and MS analyzers. Finally, some general conclusions and perspectives are given. Show less
Drouin, N.; Mever, M. van; Zhang, W.; Tobolkina, E.; Ferre, S.; Servais, A.C.; ... ; Ramautar, R. 2020
Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison... Show moreCapillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and less reproducible, notably for migration time. The latter is key for a reliable comparison of metabolic profiles and for unknown biomarker identification that is complementary to high resolution MS/MS. In this work, we present the results of a Metabo-ring trial involving 16 CE-MS platforms among 13 different laboratories spanning two continents. The goal was to assess the reproducibility and identification capability of CE-MS by employing effective electrophoretic mobility (mu(eff)) as the key parameter in comparison to the relative migration time (RMT) approach. For this purpose, a representative cationic metabolite mixture in water, pretreated human plasma, and urine samples spiked with the same metabolite mixture were used and distributed for analysis by all laboratories. The mu(eff) was determined for all metabolites spiked into each sample. The background electrolyte (BGE) was prepared and employed by each participating lab following the same protocol. All other parameters (capillary, interface, injection volume, voltage ramp, temperature, capillary conditioning, and rinsing procedure, etc.) were left to the discretion of the contributing laboratories. The results revealed that the reproducibility of the mu(eff) for 20 out of the 21 model compounds was below 3.1% vs 10.9% for RMT, regardless of the huge heterogeneity in experimental conditions and platforms across the 13 laboratories. Overall, this Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics. Show less
Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison... Show moreCapillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and less reproducible, notably for migration time. The latter is key for a reliable comparison of metabolic profiles and for unknown biomarker identification that is complementary to high resolution MS/MS. In this work, we present the results of a Metabo-ring trial involving 16 CE-MS platforms among 13 different laboratories spanning two continents. The goal was to assess the reproducibility and identification capability of CE-MS by employing effective electrophoretic mobility (mu(eff)) as the key parameter in comparison to the relative migration time (RMT) approach. For this purpose, a representative cationic metabolite mixture in water, pretreated human plasma, and urine samples spiked with the same metabolite mixture were used and distributed for analysis by all laboratories. The mu(eff) was determined for all metabolites spiked into each sample. The background electrolyte (BGE) was prepared and employed by each participating lab following the same protocol. All other parameters (capillary, interface, injection volume, voltage ramp, temperature, capillary conditioning, and rinsing procedure, etc.) were left to the discretion of the contributing laboratories. The results revealed that the reproducibility of the mu(eff) for 20 out of the 21 model compounds was below 3.1% vs 10.9% for RMT, regardless of the huge heterogeneity in experimental conditions and platforms across the 13 laboratories. Overall, this Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics. Show less
Segers, K.R.H.; Zhang, W.; Aourz, N.; Bongaerts, J.; Declerck, S.; Mangelings, D.; ... ; Eeckhaut, A. van 2020
Currently, a high variety of analytical techniques to perform metabolomics is available. One of these techniques is capillary electrophoresis coupled to mass spectrometry (CE-MS), which has emerged... Show moreCurrently, a high variety of analytical techniques to perform metabolomics is available. One of these techniques is capillary electrophoresis coupled to mass spectrometry (CE-MS), which has emerged as a rather strong analytical technique for profiling polar and charged compounds. This work aims to discover with CE-MS potential metabolic consequences of evoked seizures in plasma by using a 6Hz acute corneal seizure mouse model. CE-MS is an appealing technique because of its capability to handle very small sample volumes, such as the 10 mu L plasma samples obtained using capillary microsampling in this study. After liquid-liquid extraction, the samples were analyzed with CE-MS using low-pH separation conditions, followed by data analysis and biomarker identification. Both electrically induced seizures showed decreased values of methionine, lysine, glycine, phenylalanine, citrulline, 3-methyladenine and histidine in mice plasma. However, a second provoked seizure, 13 days later, showed a less pronounced decrease of the mean concentrations of these plasma metabolites, demonstrated by higher fold change ratios. Other obtained markers that can be related to seizure activities based on literature data, are isoleucine, serine, proline, tryptophan, alanine, arginine, valine and asparagine. Most amino acids showed relatively stable plasma concentrations between the basal levels (Time point 1) and after the 13-day wash-out period (Time point 3), which suggests its effectiveness. Overall, this work clearly demonstrated the possibility of profiling metabolite consequences related to seizure activities of an intrinsically low amount of body fluid using CE-MS. It would be useful to investigate and validate, in the future, the known and unknown metabolites in different animal models as well as in humans. Show less
The major and ultimate aim of metabolomics is to obtain an answer to a specific biological or clinical question. For that, many strategies have been applied in this field, including NMR and MS... Show moreThe major and ultimate aim of metabolomics is to obtain an answer to a specific biological or clinical question. For that, many strategies have been applied in this field, including NMR and MS-based approaches. CE-MS is one of the techniques in this field but remains underappreciated because of issues such as compromised sensitivity and poor reproducibility. In this thesis, we proposed standardized protocols for CE-MS studies using a sheathless interface and applied them in the metabolic analysis of ultra-small biological samples, such as low numbers of HepG2 cells. Another CE-MS technique used in this thesis is the traditional sheath liquid CE-MS, and it was successfully used in the metabolic profiling of plasma samples. We also introduced CE-MS with both interfaces in the field of nanosciences with our efforts in revealing the adsorption characteristics of polar metabolites to the surface of nanomaterials. This work clearly demonstrates that CE-MS can be reliably performed for metabolomics studies with acceptable repeatability. The use of sheathless CE-MS interface enables us to have in-depth profiling for ultra-small samples, and may become a powerful tool in the emerging field of single-cell analysis. Show less
Zhang, W.; Guled, F.; Hankemeier, T.; Ramautar, R. 2020
Negative ion mode nano-ESI-MS is often considered for the analysis of acidic compounds, including nucleotides. However, under high aqueous separation conditions, corona discharge is frequently... Show moreNegative ion mode nano-ESI-MS is often considered for the analysis of acidic compounds, including nucleotides. However, under high aqueous separation conditions, corona discharge is frequently observed at emitter tips, which may result in low ion abundances and reduced nano-ESI needle emitter lifetimes. In this work, we introduce a sheathless CE-MS method for the highly efficient and sensitive analysis of nucleotides employing ESI in positive ion mode, thereby fully circumventing corona discharge. By using a background electrolyte of 16 mM ammonium acetate (pH 9.7) a mixture of 12 nucleotides, composed of mono-, di-, and tri-phosphates, could be efficiently analyzed with plate numbers per meter above 220 000 and with LODs in the range from 0.06 to 1.3 nM, corresponding to 0.4 to 8.6 attomole, when using an injection volume of about 6.5 nL only. The utility of the method was demonstrated for the profiling of nucleotides in low numbers of mammalian cells using HepG2 cells as a model system. Endogenous nucleotides could be efficiently analyzed in extracts from 50 000 down to 500 HepG2 cells only. Moreover, apart from nucleotides, also some nicotinamide-adenine dinucleotides and amino acids could be analyzed under these conditions, thereby clearly illustrating the utility of this approach for metabolic profiling of low amounts of biological material. Show less
