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See detailSystems ecology of the human microbiome
Wilmes, Paul UL

Scientific Conference (2018)

Detailed reference viewed: 25 (5 UL)
See detailSystems ecology of the human microbiome
Wilmes, Paul UL

Scientific Conference (2018, November)

Detailed reference viewed: 21 (0 UL)
See detailSystems Engineering, Systems Thinking, and Learning: a Case Study in Space Industry
Moser, Hubert UL

Doctoral thesis (2013)

Systems thinking is a prerequisite of systems engineering, which is performed in multi-disciplinary teams, i.e. software engineers, mechanical engineers, electronic engineers, and others, work together to ... [more ▼]

Systems thinking is a prerequisite of systems engineering, which is performed in multi-disciplinary teams, i.e. software engineers, mechanical engineers, electronic engineers, and others, work together to develop, build, and test technical systems such as space systems. The more team members consider a systems perspective the less rework is expected and the less effort of systems engineers is required. How systems thinking evolves in practice is not sufficiently understood. Therefore, work activity of multi-disciplinary teams has been studied in an empirical study. Data from multiple sources and of different temporal resolution has been collected over four years in four studies in space systems engineering. These studies are a concept exploration project in a summer school, two concept exploration projects in a concurrent design facility, and five projects in several lifecycle stages in a small space systems company. An analytical framework has been developed based on an activity-theoretical analysis and a theme-and-key-event analysis. Contradicting multiple roles, differences in parameter definition and impact, differences in work approaches and ways of interacting, contradicting work standards, trust and doubts in extra-disciplinary decisions, awareness of diversity and orientation towards extra-disciplinary interactors, and velocity and availability of information are identified contradictions with learning potential. These contradictions provoke initiators of multi-disciplinary interaction. These are proactive provision of extra-disciplinary advice and three types of questions: critical questioning across disciplinary boundaries, asking for extra-disciplinary advice, and questioning the current work approach. The contradictions prompt the selection of themes that comprise several key events. These themes and key events are analysed on three levels (macro, meso, and micro) with a focus on systems thinking content and discourse features. Systems thinking evolves in interaction within a broad temporal range, from minutes to years. It evolves vertically, i.e. within a discipline, and horizontally, i.e. across disciplines. The evolution of systems thinking is influenced by the multi-disciplinary quality of interaction. This quality is defined by the diversity or multi-disciplinarity of the interaction, the awareness of the diversity, the orientation towards extra-disciplinary interactors, the differences in interactional responsiveness, and the cohesion of interaction. Improving the multi-disciplinary quality of interaction to foster the evolution of systems thinking is the major goal of the developed WAVES (Work Activity for a Versatile Evolution of Systems engineering and thinking) strategy. The WAVES strategy comprises two paths. The first path focuses on the introduction of employees into professional life, (space) industry, a company, a team, and a task. The second path focuses on the continuous improvement of the work activity. The implementation and evaluation of WAVES in a small space system company is the basic contribution to industry. The implementation within systems engineering departments of large space organisations has been prepared. The developed analytical framework contributes a new approach to analyse work activity in practice. Finally, the answers to the first part of the main research question contribute to a better understanding of systems engineering, systems thinking, and its learning in practice. [less ▲]

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See detailSystems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease
Krishna, Abhimanyu UL; Biryukov, Maria UL; Trefois, Christophe UL et al

in BMC Genomics (2014), 15(1154),

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often ... [more ▼]

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often used as a cellular model for Parkinson’s disease, the relevance of this cellular model in the context of Parkinson’s disease (PD) and other neurodegenerative diseases has not yet been systematically evaluated. Results: We have used a systems genomics approach to characterize the SH-SY5Y cell line using whole-genome sequencing to determine the genetic content of the cell line and used transcriptomics and proteomics data to determine molecular correlations. Further, we integrated genomic variants using a network analysis approach to evaluate the suitability of the SH-SY5Y cell line for perturbation experiments in the context of neurodegenerative diseases, including PD. Conclusions: The systems genomics approach showed consistency across different biological levels (DNA, RNA and protein concentrations). Most of the genes belonging to the major Parkinson’s disease pathways and modules were intact in the SH-SY5Y genome. Specifically, each analysed gene related to PD has at least one intact copy in SH-SY5Y. The disease-specific network analysis approach ranked the genetic integrity of SH-SY5Y as higher for PD than for Alzheimer’s disease but lower than for Huntington’s disease and Amyotrophic Lateral Sclerosis for loss of function perturbation experiments. [less ▲]

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See detailA systems level analysis of epileptogenesis-associated proteome alterations.
Keck, Michael; Androsova, Ganna UL; Gualtieri, Fabio et al

in Neurobiology of disease (2017), 105

Despite intense research efforts, the knowledge about the mechanisms of epileptogenesis and epilepsy is still considered incomplete and limited. However, an in-depth understanding of molecular ... [more ▼]

Despite intense research efforts, the knowledge about the mechanisms of epileptogenesis and epilepsy is still considered incomplete and limited. However, an in-depth understanding of molecular pathophysiological processes is crucial for the rational selection of innovative biomarkers and target candidates. Here, we subjected proteomic data from different phases of a chronic rat epileptogenesis model to a comprehensive systems level analysis. Weighted Gene Co-expression Network analysis identified several modules of interconnected protein groups reflecting distinct molecular aspects of epileptogenesis in the hippocampus and the parahippocampal cortex. Characterization of these modules did not only further validate the data but also revealed regulation of molecular processes not described previously in the context of epilepsy development. The data sets also provide valuable information about temporal patterns, which should be taken into account for development of preventive strategies in particular when it comes to multi-targeting network pharmacology approaches. In addition, principal component analysis suggests candidate biomarkers, which might inform the design of novel molecular imaging approaches aiming to predict epileptogenesis during different phases or confirm epilepsy manifestation. Further studies are necessary to distinguish between molecular alterations, which correlate with epileptogenesis versus those reflecting a mere consequence of the status epilepticus. [less ▲]

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See detailSystems medicine and integrated care to combat chronic noncommunicable diseases
Bousquet, J.; Anto, J. M.; Sterk, P. J. et al

in Genome Medicine (2011), 3(7), 43-47

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic ... [more ▼]

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems. [less ▲]

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See detailSystems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.
Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel et al

in Current pharmaceutical design (2014), 20(38), 5928-44

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health ... [more ▼]

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing). [less ▲]

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See detailSystems medicine disease maps: community-driven comprehensive representation of disease mechanisms.
Mazein, Alexander; Ostaszewski, Marek UL; Kuperstein, Inna et al

in NPJ systems biology and applications (2018), 4

The development of computational approaches in systems biology has reached a state of maturity that allows their transition to systems medicine. Despite this progress, intuitive visualisation and context ... [more ▼]

The development of computational approaches in systems biology has reached a state of maturity that allows their transition to systems medicine. Despite this progress, intuitive visualisation and context-dependent knowledge representation still present a major bottleneck. In this paper, we describe the Disease Maps Project, an effort towards a community-driven computationally readable comprehensive representation of disease mechanisms. We outline the key principles and the framework required for the success of this initiative, including use of best practices, standards and protocols. We apply a modular approach to ensure efficient sharing and reuse of resources for projects dedicated to specific diseases. Community-wide use of disease maps will accelerate the conduct of biomedical research and lead to new disease ontologies defined from mechanism-based disease endotypes rather than phenotypes. [less ▲]

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See detailSystems of Interacting Argumentation Networks
Gabbay, Dov M. UL

in Journal of Logics and their Applications (2014)

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See detailSystems-level characterization of a host-microbe metabolic symbiosis in the mammalian gut.
Heinken, Almut Katrin UL; Sahoo, Swagatika UL; Fleming, Ronan MT UL et al

in Gut microbes (2013), 4(1), 28-40

The human gut microbiota consists of ten times more microorganisms than there are cells in our body, processes otherwise indigestible nutrients, and produces important energy precursors, essential amino ... [more ▼]

The human gut microbiota consists of ten times more microorganisms than there are cells in our body, processes otherwise indigestible nutrients, and produces important energy precursors, essential amino acids, and vitamins. In this study, we assembled and validated a genome-scale metabolic reconstruction of Bacteroides thetaiotaomicron (iAH991), a prominent representative of the human gut microbiota, consisting of 1488 reactions, 1152 metabolites, and 991 genes. To create a comprehensive metabolic model of host-microbe interactions, we integrated iAH991 with a previously published mouse metabolic reconstruction, which was extended for intestinal transport and absorption reactions. The two metabolic models were linked through a joint compartment, the lumen, allowing metabolite exchange and providing a route for simulating different dietary regimes. The resulting model consists of 7239 reactions, 5164 metabolites, and 2769 genes. We simultaneously modeled growth of mouse and B. thetaiotaomicron on five different diets varying in fat, carbohydrate, and protein content. The integrated model captured mutually beneficial cross-feeding as well as competitive interactions. Furthermore, we identified metabolites that were exchanged between the two organisms, which were compared with published metabolomics data. This analysis resulted for the first time in a comprehensive description of the co-metabolism between a host and its commensal microbe. We also demonstrate in silico that the presence of B. thetaiotaomicron could rescue the growth phenotype of the host with an otherwise lethal enzymopathy and vice versa. This systems approach represents a powerful tool for modeling metabolic interactions between a gut microbe and its host in health and disease. [less ▲]

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See detailA systems-wide understanding of photosynthetic acclimation in algae and higher plants
Wanjiku Moejes, Fiona; Matuszyńska, Anna; Adhikari, Kailash et al

in Journal of Experimental Botany (2017), 68(11), 26672681

The ability of phototrophs to colonise different environments relies on robust protection against oxidative stress, a critical requirement for the successful evolutionary transition from water to land ... [more ▼]

The ability of phototrophs to colonise different environments relies on robust protection against oxidative stress, a critical requirement for the successful evolutionary transition from water to land. Photosynthetic organisms have developed numerous strategies to adapt their photosynthetic apparatus to changing light conditions in order to optimise their photosynthetic yield, which is crucial for life on Earth to exist. Photosynthetic acclimation is an excellent example of the complexity of biological systems, where highly diverse processes, ranging from electron excitation over protein protonation to enzymatic processes coupling ion gradients with biosynthetic activity, interact on drastically different timescales from picoseconds to hours. Efficient functioning of the photosynthetic apparatus and its protection is paramount for efficient downstream processes, including metabolism and growth. Modern experimental techniques can be successfully integrated with theoretical and mathematical models to promote our understanding of underlying mechanisms and principles. This review aims to provide a retrospective analysis of multidisciplinary photosynthetic acclimation research carried out by members of the Marie Curie Initial Training Project, AccliPhot, placing the results in a wider context. The review also highlights the applicability of photosynthetic organisms for industry, particularly with regards to the cultivation of microalgae. It intends to demonstrate how theoretical concepts can successfully complement experimental studies broadening our knowledge of common principles in acclimation processes in photosynthetic organisms, as well as in the field of applied microalgal biotechnology. [less ▲]

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See detailSystemwände
Weiler, Michael UL

Speeches/Talks (2013)

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See detailSYSTOMONAS — an integrated database for systems biology analysis of Pseudomonas
Choi, Claudia; Münch, Richard; Leupold, Stefan et al

in Nucleic Acids Research (2007)

Detailed reference viewed: 64 (1 UL)
See detailSzLB – Skala zur Lebensbewertung (SLB).
Ferring, Dieter UL; Filipp, Sigrun-Heide; Schmidt, Katharina

in Zeitschrift für Differentielle und Diagnostische Psychologie (1996), 17(3)

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See detailT cell immunosenescence after early life adversity: association with cytomegalovirus infection.
Elwenspoek, M.M.C.; Sias, K.; Hengesch, X. et al

in Frontiers in Immunology (2017), 8

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health ... [more ▼]

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts. [less ▲]

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See detailT wie Trottel
Heimböckel, Dieter UL

Article for general public (2012)

Detailed reference viewed: 47 (0 UL)
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See detailT(H)INK : Development of an intelligence test for primary school children.
Baudson, Tanja Gabriele UL; Preckel, F.

Scientific Conference (2010)

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See detail(T)Apping the linguistic landscape. Methodological challenges and the scientific potential of a citizen science approach to the study of social semiotics
Purschke, Christoph UL

in Linguistic Landscape (2017), 3(3),

This article explores methodological challenges and scientific perspectives of a citizen science approach to linguistic landscapes research. Starting from the outline of a disciplinary landscape, the text ... [more ▼]

This article explores methodological challenges and scientific perspectives of a citizen science approach to linguistic landscapes research. Starting from the outline of a disciplinary landscape, the text first discusses development strategies and practical implementation of crowdsourcing via mobile applications as means to data collection in two participatory research projects. The comparison highlights the complex trade-off between empirical benefits and methodological drawbacks in relation to mobile app setups for crowdsourcing. In a second step, the use of crowdsourcing technology is embedded in a methodological framework for a citizen science approach to the study of social semiotics and discussed against the background of five guiding principles: participatory research, lifeworld orientation, societal engagement, computational analysis, and open research practice. The discussion points out that a citizen science approach brings about numerous opportunities as well as substantial challenges for academic practice in terms of a democratization, social embedding, and opening of research activities. [less ▲]

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See detailT-S Fuzzy Contact State Recognition for Compliant Motion Robotic Tasks Using Gravitational Search-Based Clustering Algorithm
Jasim, Ibrahim UL; Plapper, Peter UL

in 2013 IEEE International Conference on Fuzzy Systems (FUZZ-IEEE 2013) (2013, July)

In this paper, we address the problem of contact state recognition for compliant motion robotic systems. The wrench (Cartesian forces and torques) and pose (position and orientation) of the manipulated ... [more ▼]

In this paper, we address the problem of contact state recognition for compliant motion robotic systems. The wrench (Cartesian forces and torques) and pose (position and orientation) of the manipulated object in different Contact Formations (CFs) are firstly captured during a certain task execution. Then for each CF, we develop an efficient Takagi- Sugeno (T-S) fuzzy inference system that can model that specific CF using the available input (wrench and pose) - output (the desired model output for each CF) data. The antecedent part parameters are computed using the Gravitational Search- based Fuzzy Clustering Algorithm (GS- FCA) and the consequent parts parameters are tuned by the Least Mean Square (LMS). Excellent mapping and hence recognition capabilities can be expected from the suggested scheme. In order to validate the approach; experimental test stand is built which is composed of a KUKA Light Weight Robot (LWR) manipulating a cube rigid object that interacts with an environment composed of three orthogonal planes. The manipulated object is rigidly attached to the robot arm. The robot is programmed, by a human operator, to move in different CFs and for each CF, the wrench and pose readings are captured via the Fast Research Interface (FRI) available at the KUKA LWR. Using the suggested approach, excellent modeling is obtained for different CFs during the robot task execution. A comparison with the available CF recognition approaches is also performed and the superiority of the suggested scheme is shown. [less ▲]

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