Systems ecology of microbial pioneers in the gutWilmes, Paul ![]() Presentation (2017, October) Detailed reference viewed: 33 (3 UL) Systems ecology of microbiome-human interactions: identifying which functions are keyWilmes, Paul ![]() Scientific Conference (2018, April) Detailed reference viewed: 34 (0 UL) Systems ecology of microbiomesWilmes, Paul ![]() Scientific Conference (2018, December) Detailed reference viewed: 73 (9 UL) Systems ecology of microbiomesWilmes, Paul ![]() Scientific Conference (2018, May) Detailed reference viewed: 49 (0 UL) Systems ecology of microbiomes: a new frontier of discovery in microbiologyWilmes, Paul ![]() Presentation (2017, August) Detailed reference viewed: 30 (0 UL) Systems Ecology of Microbiomes: A New Frontier of Discovery in MicrobiologyWilmes, Paul ![]() Scientific Conference (2017, May) Detailed reference viewed: 35 (0 UL) Systems ecology of microbiomes: a new frontier of discovery in microbiologyWilmes, Paul ![]() Presentation (2017, August) Detailed reference viewed: 25 (0 UL) Systems ecology of microbiomes: a new frontier of discovery in microbiologyWilmes, Paul ![]() Scientific Conference (2017, September) Detailed reference viewed: 33 (1 UL) Systems Ecology of Microbiomes: A New Frontier of Discovery in MicrobiologyWilmes, Paul ![]() Scientific Conference (2017, March) Detailed reference viewed: 33 (0 UL) Systems Ecology of microbiomes: function is keyWilmes, Paul ![]() Scientific Conference (2018, April) Detailed reference viewed: 28 (0 UL) Systems Ecology of microbiomes: identifying key functionsWilmes, Paul ![]() Scientific Conference (2018, August) Detailed reference viewed: 29 (0 UL) Systems ecology of the human microbiomeWilmes, Paul ![]() Scientific Conference (2018) Detailed reference viewed: 39 (5 UL) Systems ecology of the human microbiomeWilmes, Paul ![]() Scientific Conference (2018, November) Detailed reference viewed: 50 (0 UL) Systems ecology reveals key functions underpinning host-microbiome interactions in health and diseaseWilmes, Paul ![]() Scientific Conference (2018, June) Detailed reference viewed: 35 (0 UL) Systems Engineering, Systems Thinking, and Learning: a Case Study in Space IndustryMoser, Hubert ![]() 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 ▲] Detailed reference viewed: 263 (11 UL) Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits.; Williams, Evan ; et alin Cell (2012), 150(6), 1287-99 Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to ... [more ▼] Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders. [less ▲] Detailed reference viewed: 43 (0 UL) Systems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s diseaseKrishna, Abhimanyu ; Biryukov, Maria ; Trefois, Christophe et alin 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 ▲] Detailed reference viewed: 268 (25 UL) A systems level analysis of epileptogenesis-associated proteome alterations.; Androsova, Ganna ; et alin 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 ▲] Detailed reference viewed: 160 (7 UL) Systems medicine and integrated care to combat chronic noncommunicable diseases; ; 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 ▲] Detailed reference viewed: 121 (4 UL) Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.; ; 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 ▲] Detailed reference viewed: 125 (0 UL) |
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