Academic literature on the topic 'Pathway/network research'
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Journal articles on the topic "Pathway/network research"
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Tanabe, Shihori, Sabina Quader, Ryuichi Ono, Horacio Cabral, Kazuhiko Aoyagi, Akihiko Hirose, Hiroshi Yokozaki, and Hiroki Sasaki. "Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer." Cancers 12, no. 12 (December 18, 2020): 3833. http://dx.doi.org/10.3390/cancers12123833.
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Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.
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Sahajpal, Nikhil Shri, Ashis Mondal, Meenakshi Ahluwalia, Allan Njoroge Njau, Vamsi Kota, Nwogbo Okechukwu, Gretchen Purcell Jackson, et al. "Clinical utility of comprehensive genomic pathway and integrated network analyses in personalized oncology." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e14051-e14051. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e14051.
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e14051 Background: Adoption of next-generation sequencing (NGS) technology in routine clinical practice has enabled the detection of genetic aberrations such as single nucleotide variants, copy number alterations, and gene fusions. Pathway and network analyses (PNA) are key components for evaluation of NGS data in a clinical setting to explain findings involving thousands of altered genes and proteins with a smaller and more interpretable set of altered processes. Though PNA have been applied to identify driver genes and pathways in cohort-based analyses, its application in precision oncology remains unexplored. We investigate the potential utility of the Watson for Genomics (WfG) pathway analyses tool in interpreting complex and multiple genomic alterations in individual cancers. Methods: DNA and RNA isolated from 70 patient tumors across 30 different cancer types were processed with Illumina’s TST170 NGS platform. WfG’s feature of pathway analyses was used to identify gene variants, signaling pathways, networks, and the drugs targeting these alterations based on evidence in the clinical literature and FDA drug databases. Results: Analyses defined 5 different pathway/network models: 1) downstream therapeutic targets, 2) synthetic lethality, 3) combinatorial downstream targets + synthetic lethality, 4) two or more pathways converging to downstream targets, and 5) complex profile analyses. The five PNA models are illustrated by the following unique cases. 1) A thyroid cancer case with HRAS variant and activated RAF1 downstream pathway showed MAPK1/3 were suggestive of relevant targets. 2) An acute myeloid leukemia case with BRCA1, BRCA2 and PTEN variants, targeting a common synthetic lethal partner PARP1 was ideal for therapy. 3) A penile carcinoma case with BRAF, CDKN2A and TP53 variants, targeting the BRAF downstream pathway in combination with either CDKN2A or TP53 were the likely choice for therapy. 4) A glioma case with activated PI3K and MEK downstream pathway, targeting a common downstream marker would block both pathways. 5) A breast carcinoma case with a complex pathogenic variant profile provided relevant clinical information and levels of evidence for multiple drug targets. Conclusions: We discovered that the integrated WfG pathway analyses tool is ideal for visualization of the variants with levels of evidence from clinical literature and FDA drug databases that can help inform treatment options and provides a holistic understanding of a specific tumor profile allowing the treating clinician to select personalized targeted therapy.
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Yuan, Mengxia, Qi He, Zhiyong Long, Xiaofei Zhu, Wang Xiang, Yonghe Wu, and Shibin Lin. "Exploring the Pharmacological Mechanism of Liuwei Dihuang Decoction for Diabetic Retinopathy: A Systematic Biological Strategy-Based Research." Evidence-Based Complementary and Alternative Medicine 2021 (August 2, 2021): 1–20. http://dx.doi.org/10.1155/2021/5544518.
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Objective. To explore the pharmacological mechanism of Liuwei Dihuang decoction (LDD) for diabetic retinopathy (DR). Methods. The potential targets of LDD were predicted by PharmMapper. GeneCards and other databases were used to collect DR genes. Cytoscape was used to construct and analyze network DR and LDD’s network, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were carried out to verify the results of systematic pharmacology. Results. Five networks were constructed and analyzed: (1) diabetic retinopathy genes’ PPI network; (2) compound-compound target network of LDD; (3) LDD-DR PPI network; (4) compound-known target network of LDD; (5) LDD known target-DR PPI network. Several DR and treatment-related targets, clusters, signaling pathways, and biological processes were found. Animal experiments found that LDD can improve the histopathological changes of the retina. LDD can also increase erythrocyte filtration rate and decrease the platelet adhesion rate ( P < 0.05 ) and decrease MDA and TXB2 ( P < 0.05 ). Compared with the model group, the retinal VEGF and HIF-1α expression in the LDD group decreased significantly ( P < 0.05 ). Conclusion. The therapeutic effect of LDD on DR may be achieved by interfering with the biological processes (such as response to insulin, glucose homeostasis, and regulation of angiogenesis) and signaling pathways (such as insulin, VEGF, HIF-1, and ErbB signaling pathway) related to the development of DR that was found in this research.
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Tanabe, Shihori, Sabina Quader, Ryuichi Ono, Horacio Cabral, Kazuhiko Aoyagi, Akihiko Hirose, Hiroshi Yokozaki, and Hiroki Sasaki. "Cell Cycle Regulation and DNA Damage Response Networks in Diffuse- and Intestinal-Type Gastric Cancer." Cancers 13, no. 22 (November 18, 2021): 5786. http://dx.doi.org/10.3390/cancers13225786.
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Dynamic regulation in molecular networks including cell cycle regulation and DNA damage response play an important role in cancer. To reveal the feature of cancer malignancy, gene expression and network regulation were profiled in diffuse- and intestinal-type gastric cancer (GC). The results of the network analysis with Ingenuity Pathway Analysis (IPA) showed that the activation states of several canonical pathways related to cell cycle regulation were altered. The G1/S checkpoint regulation pathway was activated in diffuse-type GC compared to intestinal-type GC, while canonical pathways of the cell cycle control of chromosomal replication, and the cyclin and cell cycle regulation, were activated in intestinal-type GC compared to diffuse-type GC. A canonical pathway on the role of BRCA1 in the DNA damage response was activated in intestinal-type GC compared to diffuse-type GC, where gene expression of BRCA1, which is related to G1/S phase transition, was upregulated in intestinal-type GC compared to diffuse-type GC. Several microRNAs (miRNAs), such as mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451 and mir-605, were identified to have direct relationships in the G1/S cell cycle checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in epithelial-mesenchymal transition (EMT) conditions. The alterations in the activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC highlighted the significance of cell cycle regulation in EMT.
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Sirico, Marianna, Alberto D’Angelo, Caterina Gianni, Chiara Casadei, Filippo Merloni, and Ugo De Giorgi. "Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy." Cancers 15, no. 3 (January 23, 2023): 703. http://dx.doi.org/10.3390/cancers15030703.
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The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.
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Vandermeulen, Matthew D., and Paul J. Cullen. "Gene by Environment Interactions reveal new regulatory aspects of signaling network plasticity." PLOS Genetics 18, no. 1 (January 4, 2022): e1009988. http://dx.doi.org/10.1371/journal.pgen.1009988.
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Phenotypes can change during exposure to different environments through the regulation of signaling pathways that operate in integrated networks. How signaling networks produce different phenotypes in different settings is not fully understood. Here, Gene by Environment Interactions (GEIs) were used to explore the regulatory network that controls filamentous/invasive growth in the yeast Saccharomyces cerevisiae. GEI analysis revealed that the regulation of invasive growth is decentralized and varies extensively across environments. Different regulatory pathways were critical or dispensable depending on the environment, microenvironment, or time point tested, and the pathway that made the strongest contribution changed depending on the environment. Some regulators even showed conditional role reversals. Ranking pathways’ roles across environments revealed an under-appreciated pathway (OPI1) as the single strongest regulator among the major pathways tested (RAS, RIM101, and MAPK). One mechanism that may explain the high degree of regulatory plasticity observed was conditional pathway interactions, such as conditional redundancy and conditional cross-pathway regulation. Another mechanism was that different pathways conditionally and differentially regulated gene expression, such as target genes that control separate cell adhesion mechanisms (FLO11 and SFG1). An exception to decentralized regulation of invasive growth was that morphogenetic changes (cell elongation and budding pattern) were primarily regulated by one pathway (MAPK). GEI analysis also uncovered a round-cell invasion phenotype. Our work suggests that GEI analysis is a simple and powerful approach to define the regulatory basis of complex phenotypes and may be applicable to many systems.
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Hayne, Victoria, Leah A. Stein, Carole Kathleen Tremonti, Elizabeth H. Baldini, John G. Phillips, Susanna C. Hilfer, David Michael Jackman, et al. "Implementing radiation oncology pathways at Dana-Farber Cancer Institute/Brigham and Women’s Hospital." Journal of Clinical Oncology 36, no. 30_suppl (October 20, 2018): 301. http://dx.doi.org/10.1200/jco.2018.36.30_suppl.301.
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301 Background: Modern cancer care faces increasing complexity and the challenge of delivering consistent, high-quality care across growing networks. Dana-Farber Pathways address these concerns by translating expert content into treatment algorithms delivered through a web-based platform and implemented across the network. We had previously built 31 Medical Oncology (MO) pathways. Our goal was to build and implement Radiation Oncology (RO) pathways for common cancer conditions in 18 months. Methods: Partnering with lead clinicians from each disease group, we chose the most appropriate framework for each pathway: expand previously established RO pathway; use corresponding MO pathway; or if no framework was available, develop RO pathway in its entirety. We worked with each disease group to gain consensus about the recommended on-pathway selections that reflect the latest research and institutional standard of care. Implementation consisted of pre- and post-launch department communications about metric goals and individual provider training on the system. Because the program was launched without provider incentivization, the usage rate goal was navigations for at least 25% of patients receiving radiation treatment. The on-pathway rate goal range was 70-80%. Results: We exceeded our goal: we built and implemented 25 pathways in 12 months and constructed all 27 pathways in 18 months. We have met both key rate goals across all disease pathways since time of launch: usage rate is 63%; on-pathway rate is 85% (39 providers across 3 sites). Conclusions: A preliminary analysis of RO Pathway data demonstrates collective adoption across all sites. Qualitative surveys show it to be a useful resource in radiation treatment decision-making and in palliative care service. We will continue to analyze the use of RO Pathways and develop strategies to collaborate with MO to further guide multi-disciplinary decision-making.[Table: see text]
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Brougher, Laura Ione, Rocky Lee Billups, Tonya Cox, Therese Dodd, and Charles F. LeMaistre. "Development and implementation of clinical pathways across a network of blood cancer programs." Journal of Clinical Oncology 35, no. 8_suppl (March 10, 2017): 161. http://dx.doi.org/10.1200/jco.2017.35.8_suppl.161.
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161 Background: The Sarah Cannon Blood Cancer Network (SCBCN) is comprised of 7 blood cancer and Hematopoietic Cell Therapy (HCT) programs providing care for complex blood cancer patients. Network commitment to achieving standardization of care for quality and clinical platforms led to process design for development of evidence-based pathways. Methods: Standard operating procedures and a document control process were developed by the network quality management (QM). With oversight by physician leaders, initial efforts focused on standardizing patient selection criteria for HCT followed by formation of disease-specific work groups (leukemia, lymphoma, multiple myeloma, HCT). Physician-led and composed of key network team members (PharmDs, QM professionals, SCBCN leaders, research staff), the groups are responsible for developing evidence-based diagnostic and treatment pathways/algorithms for hematologic malignancies. Members participate in monthly teleconferences to develop the pathways. Annual review and deviation tracking are conducted, providing a mechanism for subsequent pathway revisions reflecting changing treatment paradigms and updated clinical evidence. QM oversees implementation and tracking across the network. Deviation tracking is managed locally using pathway-associated algorithms, with attending physician attestation to either compliance or pathway deviation/reason (e.g. co-morbidity, age, disease status, enrolled on clinical trial, other). Results are reported quarterly with review by QM. Results: See table. To date, 13 HCT pathways (18 algorithms) have been developed and released to SCBCN programs. Final approval is pending for 5 disease-based pathways (19 algorithms). Conclusions: The first compliance report will be submitted to QM in December, 2016. While deviation tracking has been paper-based, work efforts are underway to implement an electronic solution, enabling automated real-time monitoring. Implementation is expected in early 2017. [Table: see text]
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Li, Jianjie, Yuqi Gao, and Xuan Yu. "A structural analysis of the hypoxia response network." PeerJ 9 (April 6, 2021): e10985. http://dx.doi.org/10.7717/peerj.10985.
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Background The hypoxia-inducible factor-1 (HIF-1) signaling pathway is an important topic in high-altitude medicine. Network analysis is a novel method for integrating information on different aspects and levels of biological networks. However, this method has not been used in research on the HIF-1 signaling pathway network. To introduce this method into HIF-1-related research fields and verify its feasibility and effectiveness, we used a network analytical method to explore the structural attributes of the HIF-1 signaling pathway network. Methods First, we analyzed the overall network of the HIF-1 signaling pathway using information retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG). We performed topology analysis, centrality analysis, and subgroup analysis of the network. Then, we analyzed the core network based on the overall network analysis. We analyzed the properties of the topology, the bow-tie structure, and the structural complexity of the core network. Results We obtained topological structure diagrams and quantitative indicators of the overall and core networks of the HIF-1 signaling pathway. For the structure diagrams, we generated topology diagrams of the network and the bow-tie structure of the core network. As quantitative indicators, we identified topology, centrality, subgroups, the bow-tie structure, and structural complexity. The topology indicators were the number of nodes, the number of lines, the network diameter, and the network density. The centrality indicators were the degree, closeness, and betweenness. The cohesive subgroup indicator was the components of the network. The bow-tie structure indicators included the core, input, and tendril-like structures. The structural complexity indicators included a power-law fitting model and its scale parameter. Conclusions The core network could be extracted based on the subgroup analysis of the overall network of the HIF-1 signaling pathway. The critical elements of the network could be identified in the centrality analysis. The results of the study show the feasibility and effectiveness of the network analytical method used to explore the network properties of the HIF-1 signaling pathway and provide support for further research.
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He, Qiaoyu, Xiaopeng Chen, Jing Liu, Chunxia Li, Hong Xing, Yumeng Shi, and Qian Tang. "Combining Network Pharmacology with Molecular Docking for Mechanistic Research on Thyroid Dysfunction Caused by Polybrominated Diphenyl Ethers and Their Metabolites." BioMed Research International 2021 (November 17, 2021): 1–12. http://dx.doi.org/10.1155/2021/2961747.
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Network pharmacology was used to illuminate the targets and pathways of polybrominated diphenyl ethers (PBDEs) causing thyroid dysfunction. A protein-protein interaction (PPI) network was constructed. Molecular docking was applied to analyze PBDEs and key targets according to the network pharmacology results. A total of 247 targets were found to be related to 16 PBDEs. Ten key targets with direct action were identified, including the top five PIK3R1, MAPK1, SRC, RXRA, and TP53. Gene Ontology (GO) functional enrichment analysis identified 75 biological items. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified 62 pathways mainly related to the regulation of the thyroid hormone signaling pathway, MAPK signaling pathway, PI3K-Akt signaling, pathways in cancer, proteoglycans in cancer, progesterone-mediated oocyte maturation, and others. The molecular docking results showed that BDE-99, BDE-153, 5-OH-BDE47, 5 ′ -OH-BDE99, 5-BDE47 sulfate, and 5 ′ -BDE99 sulfate have a good binding effect with the kernel targets. PBDEs could interfere with the thyroid hormone endocrine through multiple targets and biological pathways, and metabolites demonstrated stronger effects than the prototypes. This research provides a basis for further research on the toxicological effects and molecular mechanisms of PBDEs and their metabolites. Furthermore, the application of network pharmacology to the study of the toxicity mechanisms of environmental pollutants provides a new methodology for environmental toxicology.
Dissertations / Theses on the topic "Pathway/network research"
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Quiedeville, Sylvain. "Ex-post assessment of impacts of research on innovations for organic farming : issues, methods, tools and instruments." Thesis, Montpellier, SupAgro, 2017. http://www.theses.fr/2017NSAM0038/document.
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Cette thèse a pour objet d’évaluer, de développer et de tester différentes méthodes qualitatives et manières d’évaluer ex-post les impacts et la contribution de la recherche sur les processus d’innovations et la société, par rapport à la transition à l’agriculture biologique.Nous avons réalisé deux cas d’études traitant de la transition à l’agriculture biologique. Le premier est le cas camarguais (en France) englobant un ensemble d’innovations techniques. Le second concerne le développement du produit biologique Ecostop pour protéger les abeilles contre la maladie de la varroatose en Bulgarie.Nous évaluons le potentiel d’une approche globale basée sur l’analyse participative du chemin de l’impact (PIPA) mais adaptée et complémentée par de nombreuses autres méthodes (premier article, partie 4), ainsi que le potentiel de l’analyse du réseau social (SNA) (deuxième article, partie 5) et de la théorie de l’acteur réseau (ANT) (troisième article, partie 6) pour l’évaluation ex-post des impacts et de la contribution de la recherche. Nous étudions les impacts de la recherche en Camargue et la manière dont ils ont été générés. Le cas Bulgare est seulement utilisé pour évaluer le potentiel d’ANT (avec le cas camarguais).L’approche basée sur PIPA permet d’évaluer avec succès les impacts et la contribution de la recherche. Nous avons pu mettre en évidence que la recherche a contribué au changement en Camargue à travers le développement d’interactions de co-apprentissage avec les producteurs bien que cela ne se soit pas avéré crucial pour le succès de l’innovation dans son ensemble. Les politiques agricoles, facteurs économiques, tests conduits indépendamment par les agriculteurs, et le cadre institutionnel, ont été les facteurs les plus importants et ayant eu le plus d’effets. En ce qui concerne SNA, il est apparu utile pour valider les dires des parties prenantes sur les relations entre acteurs ainsi que leurs implications sur la transition à l’agriculture biologique. Par exemple, le rôle grandissant joué par l’INRA (Institut National de la Recherche Agronomique) au sein du réseau d’acteurs a été confirmé de même que sa contribution à la transition vers l’agriculture biologique. Quant à l’approche ANT, elle permet de mettre en avant les relations interpersonnelles d’acteurs et leurs effets sur le développement de l’innovation. Nous soulignons en particulier l’importance des leaders d’opinion au cours des phases d’implémentation et de diffusion ; et montrons également l’importance de problématiser les questions devant être traitées afin d’améliorer le succès des programmes de rechercheThis thesis intends to evaluate, develop and test different qualitative methods and ways of ex-post assessing the impacts and contribution of the research on innovation processes and the society, in relation to the transition to organic agriculture.We have conducted two case studies focusing on the transition to organic farming. First is the Camargue case (in France) that encompasses a broad range of technical innovations. Second is on the development of the organic product Ecostop to protect bees against the varroatosis disease in Bulgaria.We evaluate the potential of a broad approach based on the Participatory Impact Pathway Analysis (PIPA) and adapted & complemented by several other methods (first article, part 4), as well as the potential of the Social Network Analysis (SNA) (second paper, part 5) and of the Actor Network Theory (ANT) (third paper, part 6), in evaluating ex-post the impacts and contribution of the research. We study the impacts of the research in the Camargue and how they were generated. The Bulgarian case is only used to evaluate the potential of ANT (together with the Camargue case).The approach based on PIPA allows assessing successfully the impacts and contribution of the research. We could show that the research contributed to change in the Camargue by developing co-learning interactions with farmers although this was not critical to the success of the innovation as a whole. The agricultural policies, economic factors, the testing conducted independently by farmers, and the institutional framework, were the most important and influential factors. With respect to SNA, it was of interest to validate stakeholders’ views on actors’ relationships and their implications on the transition to organic farming. For example, the growing role played by INRA (National Research Agronomic Institute) within the actor network was confirmed as well as its contribution to the transition. As to ANT, it allows highlighting interpersonal actors’ relationships and their effects on the innovation development. We particularly underline the importance of opinion leaders in the phases of implementation and diffusion; and also show the importance of problematizing the issues to be tackled in order to increase the success of research programs
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Stanfield, Zachary. "Comprehensive Characterization of the Transcriptional Signaling of Human Parturition through Integrative Analysis of Myometrial Tissues and Cell Lines." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1562863761406809.
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Bauer-Mehren, Anna. "Integrative approaches to investigate the molecular basis of diseases and adverse drug reactions: from multivariate statistical analysis to systems biology." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7219.
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Despite some great success, many human diseases cannot be effectively treated, prevented or cured, yet. Moreover, prescribed drugs are often not very efficient and cause undesired side effects. Hence, there is a need to investigate the molecular basis of diseases and adverse drug reactions in more detail. For this purpose, relevant biomedical data needs to be gathered, integrated and analysed in a meaningful way. In this regard, we have developed novel integrative analysis approaches based on both perspectives, classical multivariate statistics and systems biology. A novel multilevel statistical method has been developed for exploiting molecular and pharmacological information for a set of drugs in order to investigate undesired side effects. Systems biology approaches have been used to study the genetic basis of human diseases at a global scale. For this purpose, we have developed an integrated gene-disease association database and tools for user-friendly access and analysis. We showed that modularity applies for mendelian, complex and environmental diseases and identified disease-related core biological processes. We have constructed a workflow to investigate adverse drug reactions using our gene-disease association database. A detailed study of currently available pathway data has been performed to evaluate its applicability to build network models. Finally, a strategy to integrate information about sequence variations with biological pathways has been implemented to study the effect of the sequence variations onto biological processes. In summary, the developed methods are of immense practical value for other biomedical researchers and can aid to improve the understanding of the molecular basis of diseases and adverse drug reactions.
A pesar de que existen tratamientos eficaces para las enfermedades, no hay todavía una cura o un tratamiento efectivo para muchas de ellas. Asimismo los medicamentos pueden ser ineficaces o causar efectos secundarios indeseables. Por lo tanto, es necesario investigar en profundidad las bases moleculares de las enfermedades y de los efectos secundarios de los medicamentos. Para ello, es necesario identificar y analizar de forma integrada los datos biomédicos relevantes. En este sentido, hemos desarrollado nuevos métodos de análisis e integración de datos biomédicos que van desde el análisis estadístico multivariante a la biología de sistemas. En primer lugar, hemos desarrollado un nuevo método estadístico multinivel para la explotación de la información molecular y farmacológica de un conjunto de drogas a fin de investigar efectos secundarios no deseados. Luego, hemos usado métodos de biología de sistemas para estudiar las bases genéticas de enfermedades humanas a escala global. Para ello, hemos integrado en una base de datos asociaciones entre genes y enfermedades y hemos desarrollado herramientas para el fácil acceso y análisis de los datos. Mostramos que las enfermedades mendelianas, complejas y ambientales presentan modularidad e identificamos los procesos biológicos relacionados con dichas enfermedades. Hemos construido una herramienta para investigar las reacciones adversas a los medicamentos basada en nuestra base de datos de asociaciones entre genes y enfermedades. Realizamos un estudio detallado de los datos disponibles sobre los procesos biológicos para evaluar su aplicabilidad en la construcción de modelos dinámicos. Por último, desarrollamos una estrategia para integrar la información sobre las variaciones de secuencia de genes con los procesos biológicos para estudiar el efecto de dichas variaciones en los procesos biológicos.
En resumen, los métodos presentados en esta tesis constituyen una herramienta valiosa para otros investigadores y pueden ayudar a mejorar la comprensión de las bases moleculares de las enfermedades y de las reacciones adversas a los medicamentos.
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Mark, Rutenberg Richard. "COMPUTER IMAGE ANALYSIS BASED QUANTIFICATION OF COMPARATIVE IHC LEVELS OF P53 AND SIGNALING ASSOCIATED WITH THE DNA DAMAGE REPAIR PATHWAY DISCRIMINATES BETWEEN INFLAMMATORY AND DYSPLASTIC CELLULAR ATYPIA." Cleveland State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=csu1586182859848301.
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Aung, Thazin Nwe. "Molecular Mechanisms of Natural Compounds : Compound Kushen Injection (CKI) in Cancer." Thesis, 2019. http://hdl.handle.net/2440/120399.
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Chemotherapy is a treatment that uses cytotoxic drugs to kill rapidly dividing cancer cells. There are many anti-cancer chemotherapeutic drugs used alone or in combination with others to kill cancerous cells, and some of these, are of plant origin. Naturally occurring compounds, such as Taxol, are used in chemotherapy and have very specific, unique, molecular targets. However, according to the World Health Organization (Ekor, 2014), approximately eighty percent of the world’s population depends on natural compounds from traditional medicine and these compounds are widely used in complementary medicine as anti-cancer drugs (Foster et al., 2000). Traditional Chinese medicine (TCM) uses treatments that contain multiple natural compounds, a number of which have been claimed to be of therapeutic benefit to cancer sufferers (Chung et al., 2015). Some TCM preparations have shown anti-cancer, anti-migratory and anti-metastatic properties in laboratory settings (Wang et al., 2009;Pan et al., 2011;Qu et al., 2016). Research suggests that TCM natural compound mixtures might synergistically trigger therapeutic benefits through the action of multiple components affecting multiple regulatory signaling targets (Wang et al., 2008). Compound Kushen injection (CKI) is a TCM anticancer agent which has been approved by the Chinese State Food and Drug Administration to treat solid tumors in combination with chemotherapy drugs in clinics for pain relief, cancer metastasis and enhancement of the immune system since 1995, and is used to treat approximately 30,000 patients daily. Although a large body of evidence has suggested CKI has anti-cancer properties (Xu et al., 2011;Gao et al., 2018) the anti-cancer mechanisms attributable to specific compounds within the mixture remain unknown. CKI contains multiple alkaloid and flavonoid compounds and the main bioactive compounds such as matrine and oxymatrine have shown to affect cancer cells in the lab. However, other medicinal herbs containing these two compounds as main components have demonstrated patient toxicity. It is therefore important to better understand the effects of CKI, particularly with respect the contributions of individual compounds within the mixture. In this thesis, I describe a multi-disciplinary approach including analytical chemistry, cellular assays and transcriptome analysis to explore the effects of several major compounds present in CKI. Through the application of a subtractive fractionation method that removed individual compounds one, two or three at a time, I have been able to map these compounds and their interactions to specific pathways based on altered gene expression profiles. This has illuminated the roles of several major compounds of CKI, that on their own, have no, or minimal, activity in our bioassay. This approach has enabled us to identify the interactions between compounds in a mixture as shown by the response of cancer cell cultures. Using a systems biology approach along with cellular migration and invasion assays, I have mapped the activity of related proteins and pathways which may contribute to the migrastatic activity of CKI. Altogether, this thesis presents an initial characterization of the underlying mechanistic changes induced by CKI. First, by comparing differentially expressed genes across treatment combinations generated using our subtractive fractionation approach, I identified specific candidate pathways that were altered by the removal of compounds from the mixture. Second, by using transcriptome data of a breast cancer cell line, the effects of CKI on candidate anti-migratory pathways for six different cancer cell lines were assessed. These experiments identified specific candidate target pathways through which CKI might act. These approaches can be used to understand the roles and interactions of individual compounds from any complex natural compound mixture whose biological activity cannot be associated with purified compounds.Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 2019
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Singh, Arti. "Informatics Approaches to Linking Mutations to Biological Pathways, Networks and Clinical Data." Thesis, 2011. http://hdl.handle.net/1805/2608.
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Indiana University-Purdue University Indianapolis (IUPUI)The information gained from sequencing of the human genome has begun to transform human biology and genetic medicine. The discovery of functionally important genetic variation lies at the heart of these endeavors, and there has been substantial progress in understanding the common patterns of single-nucleotide polymorphism (SNP) in humans- the most frequent type of variation in humans. Although more than 99% of human DNA sequences are the same across the population, variations in DNA sequence have a major impact on how we humans respond to disease; to environmental entities such as bacteria, viruses, toxins, and chemicals; and drugs and other therapies and thus studying differences between our genomes is vital. This makes SNPs as well other genetic variation data of great value for biomedical research and for developing pharmaceutical products or medical diagnostics. The goal of the project is to link genetic variation data to biological pathways and networks data, and also to clinical data for creating a framework for translational and systems biology studies. The study of the interactions between the components of biological systems and biological pathways has become increasingly important. It is known and accepted by scientists that it as important to study different biological entities as interacting systems, as in isolation. This project has ideas rooted in this thinking aiming at the integration of a genetic variation dataset with biological pathways dataset. Annotating genetic variation data with standardized disease notation is a very difficult yet important endeavor. One of the goals of this research is to identify whether informatics approaches can be applied to automatically annotate genetic variation data with a classification of diseases.
Books on the topic "Pathway/network research"
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Workshop on Computation of Biochemical Pathways and Genetic Networks (3rd 2003 Heidelberg, Germany). 3rd Workshop on Computation of Biochemical Pathways and Genetic Networks : EML Research, Villa Bosch, Heidelberg, October 6-7, 2003. Edited by Gauges R. Berlin: Logos, 2003.
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Workshop on Computation of Biochemical Pathways and Genetic Networks (4th 2005 Heidelberg, Germany). 4th Workshop on Computation of Biochemical Pathways and Genetic Networks: A BioSim event : EML research, Villa Bosch, Heidelberg, September 12-13, 2005. Edited by Kummer U. (Ursula) and EML Research (Firm). Berlin: Logos, 2005.
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MAP kinase signaling protocols. 2nd ed. New York, N.Y: Humana Press, 2010.
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Takao, Kumazawa, Kruger Lawrence, and Mizumura Kazue, eds. The polymodal receptor: A gateway to pathological pain. Amsterdam: Elsevier, 1996.
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Simpson, Patrick K. Artificial Neural Systems: Foundations, Paradigms, Applications, and Implementations (Neural Networks, Research and Applications). Pergamon Pr, 1990.
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Simpson, Patrick K. Artificial Neural Systems: Foundations, Paradigms, Applications, and Implementations (Neural Networks, Research and Applications). Pergamon Pr, 1990.
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Simpson, Patrick K. Artificial Neural Systems: Foundations, Paradigms, Applications, and Implementations (Neural Networks, Research and Applications). Pergamon Pr, 1990.
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Simpson, Patrick K. Artificial Neural Systems: Foundations, Paradigms, Applications, and Implementations (Neural Networks, Research and Applications). Pergamon Pr, 1990.
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Simpson, Patrick K. Artificial Neural Systems: Foundations, Paradigms, Applications, and Implementations (Neural Networks, Research and Applications). Mcgraw-Hill (Tx), 1990.
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Pathways to Nursing: A Guide to Library and Online Research in Nursing and Allied Health. Information Today, 2004.
Find full textBook chapters on the topic "Pathway/network research"
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Hao, Jie, Mohammad Masum, Jung Hun Oh, and Mingon Kang. "Gene- and Pathway-Based Deep Neural Network for Multi-omics Data Integration to Predict Cancer Survival Outcomes." In Bioinformatics Research and Applications, 113–24. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-20242-2_10.
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Wang, Junbai, Ben Davidson, and Tianhai Tian. "Systems Biology Studies of Gene Network and Cell Signaling Pathway in Cancer Research." In Translational Bioinformatics, 109–29. Dordrecht: Springer Netherlands, 2013. http://dx.doi.org/10.1007/978-94-007-7975-4_6.
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Keskiner, Elif, and Ismintha Waldring. "Are “Weak Ties” Really Weak? Social Capital Reliance Among Second Generation Turkish Lawyers in Paris." In IMISCOE Research Series, 41–60. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94972-3_3.
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AbstractThe chapter studies social capital development and application among highly educated Turkish second generation working in the law sector in Paris. Previously we have demonstrated how social capital was a crucial resource in the professional pathways of Turkish second generation lawyers in Sweden, the Netherlands, France and Germany. In this chapter we take our inquiry a step further analyzing the strong and weak ties that descendants of migrants relied upon in their professional pathways. We use biographical interviews conducted with descendants of migrants in France in which they explicate their entire educational and professional trajectories. We concentrate on Turkish second generation with low-educated parents hence young people who did not receive direct professional resources from their parents.We see for this group the development of professional networks already begins in tertiary education and continues into their labour market careers. The paper aims to make contributions to several strands of the literature. Firstly, it contributes to the debate on temporality of networks by showing how distinct forms of social capital became crucial in different phases of their careers and how they relied on both weak and strong ties strategically to overcome the glass ceilings in their sectors and move upwards in their pathways. Secondly, we aim to problematize the concepts of “strong” and “weak” ties in relation to their ethnic connotations. Our study shows that second generation lawyers were able to develop relations of trust with their so-called “weak ties” while the ethnic “strong ties” represented useful clientele.
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Ellis, Claire, and Anna Triandafyllidou. "Precarity, Opportunity, and Adaptation: Recently Arrived Immigrant and Refugee Experiences Navigating the Canadian Labour Market." In IMISCOE Research Series, 101–27. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-14009-9_5.
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AbstractImmigrants and refugees have contributed significant growth in the Canadian economy over the last three decades. Despite clear advantages of a smooth transition into the labour force, many newcomers experience multiple barriers impeding their pathways to sustainable livelihoods. Further, significant increases in refugee resettlement and asylum claims in Canada since 2015 resulted in a growing number of refugee newcomers entering the labour market, often facing additional challenges of precarious legal status while seeking employment. To interrogate the settlement landscape, this chapter examines newcomers’ employment-related needs, experiences, and aspirations through a case study of migrants and refugees in Greater Toronto. Using narrative-biographic interviews, the chapter presents an ethnographic approach to examine how individual migrants navigate labour market policies and settlement dynamics during their initial years. A biographical approach allowed us to focus on the interplay of migrant agency, precarity, and adaption to both long-standing labour market dynamics as well as new barriers and enablers brought on by the shifting sands of Canada’s pandemic affected economy. The chapter highlights how emotions, decisions, and actions are inter-related and coalesce with broader structural conditions within a network of actors – individuals, networks, and institutions – to shape the labour market experiences of recently arrived immigrants and refugees.
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Seitzer, Helen, Fabian Besche-Truthe, and Michael Windzio. "Networks of Global Policy Diffusion: The Introduction of Compulsory Education." In Networks and Geographies of Global Social Policy Diffusion, 59–81. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-83403-6_3.
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AbstractCompulsory education is closely related to the reproduction and change of a country’s culture. As we know from international comparative cultural research, however, there are different pathways into modernity, and so the particular role of education for a nation-state’s cultural basis might differ as well. At the same time, different relations between countries, such as cultural similarity or trade, can function as channels of diffusion of welfare policies. Our empirical analysis tests which dimensions of global networks structure the diffusion of introduction of compulsory education. We find a positive effect of exposure to other countries in a network of cultural similarity. Policy diffusion does not proceed via economic ties and colonial histories, but does through spatial proximity.
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Koltai, Júlia, Zoltán Kmetty, and Károly Bozsonyi. "From Durkheim to Machine Learning: Finding the Relevant Sociological Content in Depression and Suicide-Related Social Media Discourses." In Pathways Between Social Science and Computational Social Science, 237–58. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-54936-7_11.
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AbstractThe phenomenon of suicide has been a focal point since Durkheim among social scientists. Internet and social media sites provide new ways for people to express their positive feelings, but they are also platforms to express suicide ideation or depressed thoughts. Most of these posts are not about real suicide, and some of them are a cry for help. Nevertheless, suicide- and depression-related content varies among platforms, and it is not evident how a researcher can find these materials in mass data of social media. Our paper uses the corpus of more than four million Instagram posts, related to mental health problems. After defining the initial corpus, we present two different strategies to find the relevant sociological content in the noisy environment of social media. The first approach starts with a topic modeling (Latent Dirichlet Allocation), the output of which serves as the basis of a supervised classification method based on advanced machine-learning techniques. The other strategy is built on an artificial neural network-based word embedding language model. Based on our results, the combination of topic modeling and neural network word embedding methods seems to be a promising way to find the research related content in a large digital corpus.Our research can provide added value in the detection of possible self-harm events. With the utilization of complex techniques (such as topic modeling and word embedding methods), it is possible to identify the most problematic posts and most vulnerable users.
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van Noordwijk, Toos (C G. E. )., Isabel Bishop, Sarah Staunton-Lamb, Alice Oldfield, Steven Loiselle, Hilary Geoghegan, and Luigi Ceccaroni. "Creating Positive Environmental Impact Through Citizen Science." In The Science of Citizen Science, 373–95. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-58278-4_19.
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AbstractInterest in citizen science is growing, including from governments and research funders. This interest is often driven by a desire for positive environmental impact, and the expectation that citizen science can deliver it by engaging the public and simultaneously collecting environmental data. Yet, in practice, there is often a gap between expected and realised impact. To close this gap, we need to better understand pathways to impact and what it takes to realise them. We articulate six key pathways through which citizen science can create positive environmental change: (1) environmental management; (2) evidence for policy; (3) behaviour change; (4) social network championing; (5) political advocacy; and (6) community action. We explore the project attributes likely to create impact through each of these pathways and show that there is an interplay between these project attributes and the needs and motivations of target participant groups. Exploring this interplay, we create a framework that articulates four citizen science approaches that create environmental impact in different ways: place-based community action; interest group investigation; captive learning research; and mass participation census.
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You, Zhu-Hong, Zhong Ming, Liping Li, and Qiao-Ying Huang. "Research on Signaling Pathways Reconstruction by Integrating High Content RNAi Screening and Functional Gene Network." In Intelligent Computing Theories and Technology, 1–10. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-39482-9_1.
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Smith, Glen. "Clothing the Emperor: Supporting National Climate Change Action in Ireland Through Local Governance Networks." In Creating Resilient Futures, 109–27. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-80791-7_6.
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AbstractThe Irish Government has set out policies and a governance framework for implementing action on climate change. However, the potential for local governance architecture to support this process has perhaps been overlooked. This chapter explores how this architecture is not an obstacle in implementing change, but a potential asset, and how it could be mobilised and enticed to deliver a lot more on climate action, sustainable development and disaster risk reduction (DRR). The coastal town of Youghal in County Cork provides an Irish case study through which the value of local governance for climate action is expounded. The chapter also recommends further research to consider the potential for local focus groups to seek sustainable pathways. The ‘sustainable pathways’ concept encourages broad input into decision points that support the selection of sustainable future trajectories, based on an understanding of risk, vulnerability and opportunity.
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Dax, Thomas. "Shaping New Rural and Mountain Narratives: Priorities for Challenges and Opportunities in Mountain Research." In Alpine Landgesellschaften zwischen Urbanisierung und Globalisierung, 33–49. Wiesbaden: Springer Fachmedien Wiesbaden, 2022. http://dx.doi.org/10.1007/978-3-658-36562-2_2.
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AbstractIn recent decades, analyses on spatial change have addressed mountains as specific and crucial places for resilience and global sustainable development pathways. Comprehensive studies have recognized the complexity of "mountain" research issues at local to global levels. This article takes stock of the emerging shift in priorities across European research towards analyzing interactions in social-ecological systems of mountain areas. The analysis builds on long-term engagement in mountain research networks, the elaboration of a European mountain research strategy, and expert interviews on key requirements for research on mountain opportunities and challenges. In order to understand the complex interrelations of mountain social-ecological systems, it is crucial to apply inter- and transdisciplinary methods enabling the elaboration of new narratives on mountain research that address pressing societal challenges.
Conference papers on the topic "Pathway/network research"
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Yang, Kailin, George-Lucian Moldovan, Patrizia Vinciguerra, Junko Murai, Shunichi Takeda, and Alan D. D'Andrea. "Abstract PR4: Regulation of the Fanconi anemia pathway by a SUMO-like delivery network." In Abstracts: Second AACR International Conference on Frontiers in Basic Cancer Research--Sep 14-18, 2011; San Francisco, CA. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.fbcr11-pr4.
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Chatterjee, Abheek, and Astrid Layton. "Bio-Inspired Human Network Design: A Multi-Currency Robustness Metric Inspired by Ecological Network Analysis." In ASME 2019 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/detc2019-98235.
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Abstract The Ecological Network Analysis (ENA) metric ecological robustness quantifies the unique balance that biological food webs have between their pathway efficiency and redundancy, enabling them to maximize their robustness to system disturbances. This robustness is a potentially desirable quality for human systems to mimic. Modeling the interactions between actors in human networks as predator-prey type exchanges (of a medium or currency rather than caloric exchanges) enables an ENA analysis. ENA has been shown to be a useful tool in improving the design of human networks because it allows the characteristics of biological networks to be mimicked. The application of these metrics is, however, limited to networks with only one flow type. Human networks are composed of many different types of flow interactions and thus a biologically-inspired indicator of total system robustness must take into account all of these interactions. This work further develops the traditional ENA ecological robustness metric to accommodate various flows between actors in multi-currency human networks. Two novel methods for quantifying multi-currency flow network robustness are introduced. The mathematical formulation for these new metrics is presented. The water network for the Kalundborg Eco-Industrial Park (EIP) is used as a case study to determine the benefits of the proposed robustness metrics. The results obtained using the single-currency robustness and the two multi-currency robustness metrics are compared using the case study. Based on the analysis of the results obtained at the system level, as well as at the sub-levels, both multi-currency metrics showed the ability to predict systems characteristics for the multi-currency Kalundborg EIP. While both of these are promising, more research regarding these metrics is needed in order to develop an elegant and comprehensive total system robustness metric.
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Amler, Hendrik, Lisa Eckey, Sebastian Faust, Marcel Kaiser, Philipp Sandner, and Benjamin Schlosser. "DeFi-ning DeFi: Challenges & Pathway." In 2021 3rd Conference on Blockchain Research & Applications for Innovative Networks and Services (BRAINS). IEEE, 2021. http://dx.doi.org/10.1109/brains52497.2021.9569795.
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DEVI, URMI, REZA PEJMAN, ZACHARY J. PHILLIPS, KALYANA B. NAKSHATRALA, AHMAD R. NAJAFI, KURT R. SCHAB, and JASON F. PATRICK. "A MULTIFUNCTIONAL AND RECONFIGURABLE MICROVASCULAR COMPOSITE." In Thirty-sixth Technical Conference. Destech Publications, Inc., 2021. http://dx.doi.org/10.12783/asc36/35898.
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Fiber-reinforced polymer (FRP) composites, consisting of stiff/strong fibers embedded within a continuous matrix, are a lightweight structural platform supporting an array of modern applications. Bioinspired vascularization of fiber-composites can augment existing performance with dynamic functionalities via liquid infiltration of the internal micro-fluidic network. Some vascular-enabled capabilities include self-healing to repair delamination damage and active-cooling to prevent thermal degradation. While such attributes have been demonstrated in separate platforms, research investigations that combine functionalities within a single composite have been limited. Here we provide a recent study that highlights a promising pathway for achieving both multifunctional, and reconfigurable behavior in microvascular FRP composites. Specifically, we detail the ability to regulate temperature and modulate electromagnetic signature via fluid substitution within the same serpentine vasculature. Varying microchannel density alters both active-cooling efficiency by water circulation and polarized radio-frequency wave reflection by liquid metal infiltration. We control these bulk property pluralities by widespread vascularization, while minimizing impact on structural performance, and decode the effects of micro-vascular topology on macromechanical behavior. Our in-depth experimental and computational investigation provides a new benchmark for future design optimization and real-world translation of multifunctional and adaptive microvascular composites.
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Hairston, Garrett, and Astrid Layton. "An Eco-Industrial Park-Based Method for Net Zero Community Creation." In ASME 2021 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2021. http://dx.doi.org/10.1115/detc2021-71440.
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Abstract Much emphasis is placed on the role of Net Zero Communities (NZCs) in achieving a sustainable future. Systems research on the topic, including the application of bio-inspired techniques already used on other human networks, is currently hindered by the lack of case studies documenting the structure and quantity of energy, water, and waste flows within realistic NZCs. This work proposes and preliminarily tests a method of generating a database of hypothetical-realistic NZCs by expanding the system boundaries for well-documented Eco-industrial Park (EIP) networks. The expansion includes residential and commercial actors from the community surrounding the EIP. Past studies using Ecological Network Analysis (ENA) to improve the environmental and economic performance of these EIPs have resulted in a quantitative database of case studies. Combining these industrial hubs to nearby residential, commercial, agricultural, etc. actors can generate potential multi-use networks on which similar design work can be conducted. Three EIP to NZC cases are generated and analyzed focusing on their system structure. Cyclicity, an ENA metric used to quantify the presence and complexity of cyclic pathways in a network, has been shown to promote the efficient use of resources in both biological and human networks. Cyclicity values for the original EIP networks, the community additions, and the potential NZC case studies reveals that there are many meaningful interactions that occur between actors that are only visible once the system boundaries are expanded to the NZC level. This offers a glimpse into the potential benefits of approaching the NZ problem, and sustainable living more generally, on a system scale — an analysis that will be further enabled by the generation of an NZC database initiated by this work.
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Ku, Kihong, Christian Jordan, and Jim Doerfler. "Pedagogical Explorations of an Open- Source Architecture Paradigm in Emerging Design Technologies." In AIA/ACSA Intersections Conference. ACSA Press, 2016. http://dx.doi.org/10.35483/acsa.aia.inter.16.1.
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Open-Source Architecture is an emerging paradigm advocating peer-to-peer collectivity, inclusiveness and participatory culture in architectural design. These conditions support a broad interest at the intersection of education, research and practice in emerging design technologies exploring formal complexity, performance, biomimicry and responsiveness. In the last decade, rich participatory, open-source communities, open-source software, and open-source hardware, created by and designed for the fields of parametric and algorithmic design, visual programming, and physical computing have emerged with resulting opportunities for change in architectural education. We discuss pedagogical approaches that introduce pathways for open-source cultures in architectural design and personal learning networks for professional development.
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Steck, Roland, and Melissa L. Knothe Tate. "Application of Stochastic Network Models for the Study of Molecular Transport Processes in Bone." In ASME 2004 International Mechanical Engineering Congress and Exposition. ASMEDC, 2004. http://dx.doi.org/10.1115/imece2004-59746.
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Osteocytes are the most abundant cells in bone. They are entombed in lacunae within the bone matrix, but are interconnected via their processes that run within the canaliculi with other osteocytes, as well as with the osteoblasts and bone lining cells on the bone surfaces, and thus from a cellular syncytium. However, the osteocytes are not immediately connected with the vasculature of bone, which means that the transport of nutrients and hormones to the cells and the removal of waste products from the cells, as well as transport of signaling molecules between the cells, has to occur either via the pericellular fluid spaces in the lacunocanalicular network, via the matrix micropores between the collagen fibers and the apatite crystals, or via intracellular transport mechanisms. Only recently our laboratory and other research groups have started to examine the transport pathways of different molecular size substances within bone systematically, using experimental tracer methods (e.g. [1, 7]). These experiments have unveiled the molecular sieving characteristics of bone: While small tracers with molecular weights of 300 Daltons (Da, e.g. glucose and small amino acids) are found in abundance throughout the bone matrix and the lacunocanalicular network, larger molecules (e.g. cytokines and serum derived proteins) are only transported through the pericellular spaces of the lacunocanalicular network. Furthermore, the transport of these substances through the lacunocanalicular network can be enhanced by mechanical loading of bone [1]. These findings highlight the importance of the lacunocanalicular network for the survival of the osteocytes and thereby tissue health. However, the state of the osteocyte syncytium is affected by age and bone diseases. It has been shown that the number of osteocytes in cortical bone decreases with age [6]. Furthermore, a histological study of cortical bone tissue samples from donors undergoing hip replacement surgery has shown that the morphology of the lacunocanalicular network is altered in diseased bone [2].
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Cusack, Tara, Nicola Mountford, Minna Isomursu, Guido Giunti Garcia, Dimitris Filos, and Ioanna Chouvarda. "INTERDISCIPLINARY AND INTERSECTORAL DOCTORAL EDUCATION DESIGNED TO IMPROVE GRADUATE EMPLOYABILITY." In International Conference on Education and New Developments. inScience Press, 2021. http://dx.doi.org/10.36315/2021end136.
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Typically, less than half of doctoral graduates will be employed in academia immediately after graduation, with less than 10%-15% achieving a long-term academic career. This leaves 85-90% of PhD graduates seeking employment outside the academic setting, for example in industry and government. The objective of the CHAMELEONS study (CHampioning A Multi-sectoral Education and Learning Experience to Open New pathways for doctoral Students) is to develop innovative educational interventions that shape more adaptable, entrepreneurial, and employable graduates, ready to meet the challenges of the future. Stakeholders from the connected health industry, clinical care, charities, patients, patient representatives, government, recent doctoral graduates, and academics were invited to participate in a “World Café” participatory method for collecting qualitative data. Owing to the COVID-19 health situation this took place via Zoom. Analysis of the results revealed 4 key learning objectives for doctoral graduates to: 1. Develop networking and communication skills. 2. Understand user centred research design. 3. Market research capacity and research skills. 4. Build an understanding of themselves and others. This led to the development of three bespoke doctoral modules: 1. Forging relationships: Building and Sustaining your Doctoral Network; 2. Managing the Project: Keeping on Track with an Eye to the future; Module 3: Starting your Career: Future Proofing your Career and Getting a Job. These modules are available to doctoral students across five European Universities.
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Ghezzi, Diego, Andrea Menegon, Alessandra Pedrocchi, Sara Mantero, Flavia Valtorta, and Giancarlo Ferrigno. "PhotoMEA: A New Step Towards Total Optical Analysis of In Vitro Neuronal Networks." In ASME 8th Biennial Conference on Engineering Systems Design and Analysis. ASMEDC, 2006. http://dx.doi.org/10.1115/esda2006-95218.
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Light stimulation of neurons is a promising approach for investigating the molecular mechanisms at the basis of neuronal physiology and plasticity. In particular, flash photolysis of caged compounds offers the unique advantage of allowing to quickly change the concentration of either intracellular or extracellular bioactive molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. In this field of research, we describe a simple laser-based set-up for the local activation of caged compounds. The coupling of a UV laser diode to a small-core optical fibre allows to reduce the uncaging area and to quickly change the stimulation point. The actual localisation of the light stimulation is determined using a caged fluorescent compound (dextran, DMNB-caged fluorescein). The efficiency of our set up for neuronal stimulation is tested with a caged neurotransmitter (MNI-caged-L-glutamate). Activation of caged glutamate evokes neuronal responses that are recorded using a MicroElectrode Array system and/or following the variations in the concentrations of the Cai2+. This work shows that our laser-based set-up is a powerful tool for local activation of caged compound allowing a unique opportunity to follow the effects of local neuronal pathways on neuronal network activity, for instance during pharmacological and toxicological treatments.
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Zeiner, Herwig, Roland Unterberger, Dietmar Maurer, Silvia Russegger, and Lucas Paletta. "Office-Based Workplace Monitoring and Time-Aware Feedback by using Ambient IoT Sensors." In 13th International Conference on Applied Human Factors and Ergonomics (AHFE 2022). AHFE International, 2022. http://dx.doi.org/10.54941/ahfe1001834.
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During the COVID pandemic, our understanding of a workplace (e.g. office building, home office, other offices) has changed. For example, we are constantly changing our workspace in office jobs. It is a post-COVID phenomenon that we change our work environment more frequently and more often during a week. In this paper, we investigate what sensors and software tools we need to determine that we are working in ideal conditions, including good air quality, low CO2, etc. From an employee’s point of view, it is interesting if such monitoring devices can be easily used and combined. The evaluation should be possible and combinable by simple means. Why is this difficult? Considering that there is no common agreement among researchers on the definition of workplaces and new hybrid workplaces (i.e. office in company building, home office, and third office places) make the challenges even more complex. In this context, quantitative data from novel low-cost biosensors, such as for measuring carbon dioxide concentration distribution, highlighting the presence and attention of employees and their change in behavior within a working environment, are discussed, and the paper also provides an outlook towards novel research pathways for using a connected network of IoT devices and ambient biosensor technologies.
Reports on the topic "Pathway/network research"
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Friedman, Haya, Julia Vrebalov, and James Giovannoni. Elucidating the ripening signaling pathway in banana for improved fruit quality, shelf-life and food security. United States Department of Agriculture, October 2014. http://dx.doi.org/10.32747/2014.7594401.bard.
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Background : Banana being a monocot and having distinct peel and pulp tissues is unique among the fleshy fruits and hence can provide a more comprehensive understanding of fruit ripening. Our previous research which translated ripening discoveries from tomato, led to the identification of six banana fruit-associated MADS-box genes, and we confirmed the positive role of MaMADS1/2 in banana ripening. The overall goal was to further elucidate the banana ripening signaling pathway as mediated by MADS-boxtranscriptional regulators. Specific objectives were: 1) characterize transcriptional profiles and quality of MaMADS1/2 repressed fruit; 2) reveal the role of additional MaMADSgenes in ripening; 3) develop a model of fruit MaMADS-box mode of action; and 4) isolate new components of the banana ripening signaling pathway. Major conclusion: The functions of the banana MaMADS1-5 have been examined by complimenting the rinor the TAGL1-suppressed lines of tomato. Only MaMADS5 exhibited partial complementation of TAGL1-suppressed and rinlines, suggesting that while similar genes play corresponding roles in ripening, evolutionary divergence makes heterologous complementation studies challenging. Nevertheless, the partial complementation of tomato TAGL1-surpessed and rinlines with MaMADS5 suggests this gene is likely an important ripening regulator in banana, worthy of further study. RNA-seqtranscriptome analysis during ripening was performed on WT and MaMADS2-suppressed lines revealing additional candidate genes contributing to ripening control mechanisms. In summary, we discovered 39 MaMADS-box genes in addition to homologues of CNR, NOR and HB-1 expressed in banana fruits, and which were shown in tomato to play necessary roles in ripening. For most of these genes the expression in peel and pulp was similar. However, a number of key genes were differentially expressed between these tissues indicating that the regulatory components which are active in peel and pulp include both common and tissue-specific regulatory systems, a distinction as compared to the more uniform tomato fruit pericarp. Because plant hormones are well documented to affect fruit ripening, the expressions of genes within the auxin, gibberellin, abscisic acid, jasmonic acid, salicylic and ethylene signal transduction and synthesis pathways were targeted in our transcriptome analysis. Genes’ expression associated with these pathways generally declined during normal ripening in both peel and pulp, excluding cytokinin and ethylene, and this decline was delayed in MaMADS2-suppressed banana lines. Hence, we suggest that normal MaMADS2 activity promotes the observed downward expression within these non-ethylene pathways (especially in the pulp), thus enabling ripening progression. In contrast, the expressions of ACSand ACOof the ethylene biosynthesis pathway increase in peel and pulp during ripening and are delayed/inhibited in the transgenic bananas, explaining the reduced ethylene production of MaMADS2-suppressed lines. Inferred by the different genes’ expression in peel and pulp of the gibberellins, salicylic acid and cytokinins pathways, it is suggested that hormonal regulation in these tissues is diverse. These results provide important insights into possible avenues of ripening control in the diverse fruit tissues of banana which was not previously revealed in other ripening systems. As such, our transcriptome analysis of WT and ripening delayed banana mutants provides a starting point for further characterization of ripening. In this study we also developed novel evidence that the cytoskeleton may have a positive role in ripening as components of this pathway were down-regulated by MaMADS2 suppression. The mode of cytoskeleton involvement in fruit ripening remains unclear but presents a novel new frontier in ripening investigations. In summary, this project yielded functional understanding of the role and mode of action of MaMADS2 during ripening, pointing to both induction of ethylene and suppression of non-ethylene hormonal singling pathways. Furthermore, our data suggest important roles for cytoskeleton components and MaMADS5 in the overall banana ripening control network. Implications: The project revealed new molecular components/genes involved in banana ripening and refines our understanding of ripening responses in the peel and pulp tissues of this important species. This information is novel as compared to that derived from the more uniform carpel tissues of other highly studied ripening systems including tomato and grape. The work provides specific target genes for potential modification through genetic engineering or for exploration of useful genetic diversity in traditional breeding. The results from the project might point toward improved methods or new treatments to improve banana fruit storage and quality.
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Taylor, Joe, Evert-jan Quak, James Georgalakis, and Louise Clark. Pathways to Impact in the Pandemic. Institute of Development Studies, September 2022. http://dx.doi.org/10.19088/cc.2022.003.
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Implementing and ascertaining impact and outcomes of research is a prolonged process that may take several years due to complexities in bureaucratic, social, and economic systems. At the macro level, collective reflection on the different methods and approaches that research projects use to promote uptake and impact is rare but has potential to encourage learning and exchanges between different funders and projects around impact pathways as useful road maps for research. The Covid-19 pandemic has changed the nature of research – while it has increased the demand for evidence to inform decision-making, it has further disrupted both the policy-influencing and engagement activities that would usually accompany such research. This report is based on an analysis of 90 research projects supported by the Covid Collective, COVID CIRCLE, and Covid Response for Equity (CORE) initiatives. It provides an overview and insight into how different funders and initiatives were working to facilitate change in the context of the Covid-19 pandemic. In line with the Economic and Social Research Council (ESRC) definitions of ‘impact’, and subsequent work by the ESRC-FCDO’s (Foreign, Commonwealth & Development Office) Impact Initiative, four categories were used to map the emerging outcomes and different types of change. These outcome areas comprise capacity, networks, conceptual, and instrumental outcomes. Outcome examples were then classified into more detailed descriptive groups highlighted in Table 1.
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Lers, Amnon, and Gan Susheng. Study of the regulatory mechanism involved in dark-induced Postharvest leaf senescence. United States Department of Agriculture, January 2009. http://dx.doi.org/10.32747/2009.7591734.bard.
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Postharvest leaf senescence contributes to quality losses in flowers and leafy vegetables. The general goal of this research project was to investigate the regulatory mechanisms involved in dark-induced leaf senescence. The regulatory system involved in senescence induction and control is highly complex and possibly involves a network of senescence promoting pathways responsible for activation of the senescence-associated genes. Pathways involving different internal signals and environmental factors may have distinctive importance in different leaf senescence systems. Darkness is known to have a role in enhancement of postharvest leaf senescence and for getting an insight into its regulatory mechanism/s we have applied molecular genetics and functional genomics approaches. The original objectives were: 1. Identification of dark-induced SAGs in Arabidopsis using enhancer/promoter trap lines and microarray approaches; 2. Molecular and functional characterization of the identified genes by analyzing their expression and examining the phenotypes in related knockout mutant plants; 3. Initial studies of promoter sequences for selected early dark-induced SAGs. Since genomic studies of senescence, with emphasis on dark-induced senescence, were early-on published which included information on potential regulatory genes we decided to use this new information. This is instead of using the uncharacterized enhancer/promoter trap lines as originally planned. We have also focused on specific relevant genes identified in the two laboratories. Based on the available genomic analyses of leaf senescence 10 candidate genes hypothesized to have a regulatory role in dark-induced senescence were subjected to both expression as well as functional analyses. For most of these genes senescence-specific regulation was confirmed, however, functional analyses using knock-out mutants indicated no consequence to senescence progression. The transcription factor WARK75 was found to be specifically expressed during natural and dark-induced leaf senescence. Functional analysis demonstrated that in detached leaves senescence under darkness was significantly delayed while no phenotypic consequences could be observed on growth and development, including no effect on natural leaf senescence,. Thus, WARKY75 is suggested to have a role in dark-induced senescence, but not in natural senescence. Another regulatory gene identified to have a role in senescence is MKK9 encoding for a Mitogen-Activated Protein Kinase Kinase 9 which is upregulated during senescence in harvested leaves as well as in naturally senescing leaves. MKK9 can specifically phosphorylate another kinase, MPK6. Both knockouts of MKK9 and MPK6 displayed a significantly senescence delay in harvested leaves and possibly function as a phosphorelay that regulates senescence. To our knowledge, this is the first report that clearly demonstrates the involvement of a MAP kinase pathway in senescence. This research not only revealed a new signal transduction pathway, but more important provided significant insights into the regulatory mechanisms underlying senescence in harvested leaves. In an additional line of research we have employed the promoter of the senescence-induced BFN1 gene as a handle for identifying components of the regulatory mechanism. This gene was shown to be activated during darkinduced senescence of detached leaves, as well as natural senescence. This was shown by following protein accumulation and promoter activity which demonstrated that this promoter is activated during dark-induced senescence. Analysis of the promoter established that, at least some of the regulatory sequences reside in an 80 bps long fragment of the promoter. Overall, progress was made in identification of components with a role in dark-induced senescence in this project. Further studies should be done in order to better understand the function of these components and develop approaches for modulating the progress of senescence in crop plants for the benefit of agriculture.
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Tucker-Blackmon, Angelicque. Engagement in Engineering Pathways “E-PATH” An Initiative to Retain Non-Traditional Students in Engineering Year Three Summative External Evaluation Report. Innovative Learning Center, LLC, July 2020. http://dx.doi.org/10.52012/tyob9090.
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The summative external evaluation report described the program's impact on faculty and students participating in recitation sessions and active teaching professional development sessions over two years. Student persistence and retention in engineering courses continue to be a challenge in undergraduate education, especially for students underrepresented in engineering disciplines. The program's goal was to use peer-facilitated instruction in core engineering courses known to have high attrition rates to retain underrepresented students, especially women, in engineering to diversify and broaden engineering participation. Knowledge generated around using peer-facilitated instruction at two-year colleges can improve underrepresented students' success and participation in engineering across a broad range of institutions. Students in the program participated in peer-facilitated recitation sessions linked to fundamental engineering courses, such as engineering analysis, statics, and dynamics. These courses have the highest failure rate among women and underrepresented minority students. As a mixed-methods evaluation study, student engagement was measured as students' comfort with asking questions, collaboration with peers, and applying mathematics concepts. SPSS was used to analyze pre-and post-surveys for statistical significance. Qualitative data were collected through classroom observations and focus group sessions with recitation leaders. Semi-structured interviews were conducted with faculty members and students to understand their experiences in the program. Findings revealed that women students had marginalization and intimidation perceptions primarily from courses with significantly more men than women. However, they shared numerous strategies that could support them towards success through the engineering pathway. Women and underrepresented students perceived that they did not have a network of peers and faculty as role models to identify within engineering disciplines. The recitation sessions had a positive social impact on Hispanic women. As opportunities to collaborate increased, Hispanic womens' social engagement was expected to increase. This social engagement level has already been predicted to increase women students' persistence and retention in engineering and result in them not leaving the engineering pathway. An analysis of quantitative survey data from students in the three engineering courses revealed a significant effect of race and ethnicity for comfort in asking questions in class, collaborating with peers outside the classroom, and applying mathematical concepts. Further examination of this effect for comfort with asking questions in class revealed that comfort asking questions was driven by one or two extreme post-test scores of Asian students. A follow-up ANOVA for this item revealed that Asian women reported feeling excluded in the classroom. However, it was difficult to determine whether these differences are stable given the small sample size for students identifying as Asian. Furthermore, gender differences were significant for comfort in communicating with professors and peers. Overall, women reported less comfort communicating with their professors than men. Results from student metrics will inform faculty professional development efforts to increase faculty support and maximize student engagement, persistence, and retention in engineering courses at community colleges. Summative results from this project could inform the national STEM community about recitation support to further improve undergraduate engineering learning and educational research.
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Fromm, Hillel, Paul Michael Hasegawa, and Aaron Fait. Calcium-regulated Transcription Factors Mediating Carbon Metabolism in Response to Drought. United States Department of Agriculture, June 2013. http://dx.doi.org/10.32747/2013.7699847.bard.
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Original objectives: The long-term goal of the proposed research is to elucidate the transcription factors, genes and metabolic networks involved in carbon metabolism and partitioning in response to water deficit. The proposed research focuses on the GTLcalcium/calmodulinbindingTFs and the gene and metabolic networks modulated by these TFs in Arabidopsis thaliana. The specific objectives are as follows. Objective-1 (USA): Physiological analyses of GTL1 loss- and gain-of-function plants under water sufficient and drought stress conditions Objective 2 (USA / Israel-TAU): Characterizion of GTL target genes and bioinformatic analysis of data to eulcidate gene-network topology. Objective-3 (Israel-TAU): Regulation of GTLmediated transcription by Ca²⁺/calmodulin: mechanism and biological significance. Objective-4 (Israel-BGU): Metabolic networks and carbon partitioning in response to drought. Additional direction: In the course of the project we added another direction, which was reported in the 2nd annual report, to elucidate genes controlling drought avoidance. The TAU team has isolated a few unhydrotropic (hyd) mutants and are in the process of mapping these mutations (of hyd13 and hyd15; see last year's report for a description of these mutants under salt stress) in the Arabidopsis genome by map-based cloning and deep sequencing. For this purpose, each hyd mutant was crossed with a wild type plant of the Landsberg ecotype, and at the F2 stage, 500-700 seedlings showing the unhydrotropic phenotype were collected separately and pooled DNA samples were subkected to the Illumina deep sequencing technology. Bioinformatics were used to identify the exact genomic positions of the mutations (based on a comparison of the genomic sequences of the two Arabidopsis thaliana ecotypes (Columbia and Landsberg). Background: To feed the 9 billion people or more, expected to live on Earth by the mid 21st century, the production of high-quality food must increase substantially. Based on a 2009 Declaration of the World Summit on Food Security, a target of 70% more global food production by the year 2050 was marked, an unprecedented food-production growth rate. Importantly, due to the larger areas of low-yielding land globally, low-yielding environments offer the greatest opportunity for substantial increases in global food production. Nowadays, 70% of the global available water is used by agriculture, and 40% of the world food is produced from irrigated soils. Therefore, much needs to be done towards improving the efficiency of water use by plants, accompanied by increased crop yield production under water-limiting conditions. Major conclusions, solutions and achievements: We established that AtGTL1 (Arabidopsis thaliana GT-2 LIKE1) is a focal determinant in water deficit (drought) signaling and tolerance, and water use efficiency (WUE). The GTL1 transcription factor is an upstream regulator of stomatal development as a transrepressor of AtSDD1, which encodes a subtilisin protease that activates a MAP kinase pathway that negatively regulates stomatal lineage and density. GTL1 binds to the core GT3 cis-element in the SDD1 promoter and transrepresses its expression under water-sufficient conditions. GTL1 loss-of-function mutants have reduced stomatal number and transpiration, and enhanced drought tolerance and WUE. In this case, higher WUE under water sufficient conditions occurs without reduction in absolute biomass accumulation or carbon assimilation, indicating that gtl1-mediated effects on stomatal conductance and transpiration do not substantially affect CO₂ uptake. These results are proof-of-concept that fine-tuned regulation of stomatal density can result in drought tolerance and higher WUE with maintenance of yield stability. Implications: Accomplishments during the IS-4243-09R project provide unique tools for continued discovery research to enhance plant drought tolerance and WUE.
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Chen, Xiaole, Peng Wang, Yunquan Luo, Yi-Yu Lu, Wenjun Zhou, Mengdie Yang, Jian Chen, Zhi-Qiang Meng, and Shi-Bing Su. Therapeutic Efficacy Evaluation and Underlying Mechanisms Prediction of Jianpi Liqi Decoction for Hepatocellular Carcinoma. Science Repository, September 2021. http://dx.doi.org/10.31487/j.jso.2021.02.04.sup.
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Objective: The aim of this study was to assess the therapeutic effects of Jianpi Liqi decoction (JPLQD) in hepatocellular carcinoma (HCC) and explore its underlying mechanisms. Methods: The characteristics and outcomes of HCC patients with intermediate stage B who underwent sequential conventional transcatheter arterial chemoembolization (cTACE) and radiofrequency ablation (RFA) only or in conjunction with JPLQD were analysed retrospectively. The plasma proteins were screened using label-free quantitative proteomics analysis. The effective mechanisms of JPLQD were predicted through network pharmacology approach and partially verified by ELISA. Results: Clinical research demonstrated that the Karnofsky Performance Status (KPS), traditional Chinese medicine (TCM) syndrome scores, neutropenia and bilirubin, median progression-free survival (PFS), and median overall survival (OS) in HCC patients treated with JPLQD were superior to those in patients not treated with JPLQD (all P<0.05). The analysis of network pharmacology, combined with proteomics, suggested that 52 compounds targeted 80 potential targets, which were involved in the regulation of multiple signaling pathways, especially affecting the apoptosis-related pathways including TNF, p53, PI3K-AKT, and MAPK. Plasma IGFBP3 and CA2 were significantly up-regulated in HCC patients with sequential cTACE and RFA therapy treated with JPLQD than those in patients not treated with JPLQD (P<0.001). The AUC of the IGFBP3 and CA2 panel, estimated using ROC analysis for JPLQD efficacy evaluation, was 0.867. Conclusion: These data suggested that JPLQD improves the quality of life, prolongs the overall survival, protects liver function in HCC patients, and exhibits an anticancer activity against HCC. IGFBP3 and CA2 panels may be potential therapeutic targets and indicators in the efficacy evaluation for JPLQD treatment, and the effective mechanisms involved in the regulation of multiple signaling pathways, possibly affected the regulation of apoptosis.
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Taylor, Peter, and Crystal Tremblay. Decolonising Knowledge for Development in the Covid-19 Era. Institute of Development Studies (IDS), March 2022. http://dx.doi.org/10.19088/ids.2022.018.
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This Working Paper seeks to explore current and emerging framings of decolonising knowledge for development. It does this with the intent of helping to better understand the importance of diverse voices, knowledges, and perspectives in an emerging agenda for development research. It aims to offer conceptual ideas and practical lessons on how to engage with more diverse voices and perspectives in understanding and addressing the impacts of Covid-19. The authors situate their thoughts and reflections around experiences recently shared by participants in international dialogues that include the Covid Collective; an international network of practitioners working in development contexts; engagement and dialogue with Community-based Research Canada, and their work with the Victoria Forum. Through these stories and reflections, they bring together key themes, tensions, and insights on the decolonisation of knowledge for development in the context of the Covid-19 era as well as offering some potential ways forward for individuals and organisations to transform current knowledge inequities and power asymmetries. These pathways, among other solutions identified, call for the inclusion of those whose challenges are being addressed, reflective spaces for inclusive processes, and connection, sharing and demonstrating the value of decolonised knowledge for liberation and trust.
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Dale, Naomi, Aneesa Khan, and Sophie Dale. Early intervention for vision and neurodevelopment in infants and very young children with visual impairment: a systematicreview. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, August 2022. http://dx.doi.org/10.37766/inplasy2022.8.0080.
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Review question / Objective: Research question - What is the effectiveness of Early Childhood Intervention (ECI) in the first 3 years of life? Population (P) Infants and very young children with diagnosed visual impairment. Intervention (I) ECI programmes that includes vision and developmental stimulation, play, learning and responsive parenting Comparison (C) Standard care or control Outcomes (O) Primary: Vision function or and/or neurodevelopment and/or parent-child interaction outcomes Secondary: Parental context factors eg parental wellbeing and mental health, parental satisfaction with service provision. Condition being studied: Childhood congenital or very early visual impairment arising from congenital disorders of the peripheral or anterior visual system or cerebral-based vision disorders. This includes all vision disorders of the globe, retina and anterior optic nerve and all vision disorders that are considered cerebral based along visual pathways that are retro-chiasmatic and include central brain regions and networks involved in vision processing.
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Reeve, Sophie, Susanna Cartmell, Alice Mutimer, and Olivia Frost. e-Dialogues Spark Debate on the Dynamics of Agricultural Commercialisation. APRA, Future Agricultures Consortium, April 2022. http://dx.doi.org/10.19088/apra.2022.029.
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In early 2022, the Agricultural Policy Research in Africa (APRA) Programme of the Future Agricultures Consortium (FAC), in partnership with the United Nations Sustainable Development Solutions Network and Foresight4Food, held an e-Dialogue series: Towards an Equitable and Sustainable Transformation of Food Systems. This followed an earlier, highly successful series organised with the same partners in the second half of 2020 on What Future for Small-Scale Farming? The latest series included three online Zoom sessions led by APRA over January-March 2022 on topics including COVID-19 and its effects on local food systems and rural livelihoods, and transition pathways and strategies for supporting more equitable and resilient food systems in Africa. These virtual events were designed to replace an international conference that was part of APRA’s original end-of-programme plan, before the COVID-19 crisis prevented large, physical gatherings. The three e-Dialogues brought together APRA researchers and expert commentators from across sub-Saharan Africa, as well as a wider audience. The objective of these dialogues was to examine evidence and lessons from APRA’s six-year collaborative research programme (2016-22) analysing the dynamics of agricultural commercialisation processes, agrarian change and rural transformation in the region. This report looks at their impact, what worked well, and what could have been improved.
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Olszewski, Neil, and David Weiss. Role of Serine/Threonine O-GlcNAc Modifications in Signaling Networks. United States Department of Agriculture, September 2010. http://dx.doi.org/10.32747/2010.7696544.bard.
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Significant evidence suggests that serine/threonine-O-linked N-acetyl glucosamine0-(GlcNAc) modifications play a central role in the regulation of plant signaling networks. Forexample, mutations in SPINDLY,) SPY (an O-GlcNAc transferase,) OGT (promote gibberellin GA) (signal transduction and inhibit cytokinin responses. In addition, mutating both Arabidopsis OGTsSEC (and SPY) causes embryo lethality. The long-term goal of this research is to elucidate the mechanism by which Arabidopsis OGTs regulate signaling networks. This project investigated the mechanisms of O-GlcNAc regulation of cytokinin and gibberellin signaling, identified additional processes regulated by this modification and investigated the regulation of SEC activity. Although SPY is a nucleocytoplasmic protein, its site of action and targets were unknown. Severalstudies suggested that SPY acted in the nucleus where it modified nuclear components such as the DELLA proteins. Using chimeric GFP-SPY fused to a nuclear-export signal or to a nuclear-import signal, we showed that cytosolic, but not nuclear SPY, regulated cytokinin and GA signaling. We also obtained evidence suggesting that GA and SPY affect cytokinin signaling via a DELLA-independent pathway. Although SEC and SPY were believed to have overlapping functions, the role of SEC in cytokinin and GA signaling was unclear. The role of SEC in cytokinin and GA responses was investigated by partially suppressing SPY expression in secplants using a synthetic Spymicro RNA miR(SPY). The possible contribution of SEC to the regulation of GA and cytokinin signaling wastest by determining the resistance of the miR spy secplants to the GA biosynthesis inhibitor paclobutrazol and to cytokinin. We found that the transgenic plants were resistant to paclobutrazol and to cytokinin, butonlyata level similar to spy. Moreover, expressing SEC under the 35S promoter in spy mutant did not complement the spy mutation. Therefore, we believe that SEC does not act with SPY to regulate GA or cytokinin responses. The cellular targets of Spy are largely unknown. We identified the transcription factor TCP15 in a two-hybrid screen for SPY-interacting proteins and showed that both TCP15 and its closely homolog TCP14 were O-GlcNAc modified by bacterially-produced SEC. The significance of the interaction between SPY and these TCPs was examined by over-expressing the minwild-type and spy-4plants. Overexpression of TCP14 or TCP15 in wild-type background produced phenotypes typical of plants with increased cytokinin and reduced GA signaling. TCP14 overexpression phenotypes were strongly suppressed in the spy background, suggesting that TCP14 and TCP15 affect cytokinin and GA signaling and that SPY activates them. In agreement with this hypothesis, we created a tcp14tcp15 double mutant and found that it has defects similar to spyplants. In animals, O-GlcNAc modification is proposed to regulate the activity of the nuclear pore. Therefore, after discovering that SEC modified a nucleoporinNUP) (that also interacts with SPY, we performed genetic experiments exploring the relationship between NUPs and SPY nupspy double mutants exhibited phenotypes consistent with SPY and NUPs functioning in common processes and nupseeds were resistant to GA biosynthesis inhibitors. All eukaryotic OGTs have a TPR domain. Deletion studies with bacterially-expressed SEC demonstrated SEC'sTPR domain inhibits SEC enzymatic activity. Since the TPR domain interacts with other proteins, we propose that regulatory proteins regulate OGT activity by binding and modulating the inhibitory activity of the TPR domain.