Mutations in the HER2 kinase domain have been identified in human clinical lung cancer specimens. Here we demonstrate that inducible expression of the most common HER2 mutant (HER2...) in mouse lung ...epithelium causes invasive adenosquamous carcinomas restricted to proximal and distal bronchioles. Continuous expression of HER2... is essential for tumor maintenance, suggesting a key role for HER2 in lung adenosquamous tumorigenesis. Preclinical studies assessing the in vivo effect of erlotinib, trastuzumab, BIBW2992, and/or rapamycin on HER2YVMA transgenic mice or H1781 xenografts with documented tumor burden revealed that the combination of BIBW2992 and rapamycin is the most effective treatment paradigm causing significant tumor shrinkage. Immunohistochemical analysis of lung tumors treated with BIBW2992 and rapamycin combination revealed decreased phosphorylation levels for proteins in both upstream and downstream arms of MAPK and Akt/mTOR signaling axes, indicating inhibition of these pathways. Based on these findings, clinical testing of the BIBW2992/rapamycin combination in non-small cell lung cancer patients with tumors expressing HER2 mutations is warranted. (ProQuest: ... denotes formulae/symbols omitted.)
Mutations in the HER2 kinase domain have been identified in human clinical lung cancer specimens. Here we demonstrate that inducible expression of the most common HER2 mutant (HER2
YVMA
) in mouse ...lung epithelium causes invasive adenosquamous carcinomas restricted to proximal and distal bronchioles. Continuous expression of HER2
YVMA
is essential for tumor maintenance, suggesting a key role for HER2 in lung adenosquamous tumorigenesis. Preclinical studies assessing the in vivo effect of erlotinib, trastuzumab, BIBW2992, and/or rapamycin on HER2
YVMA
transgenic mice or H1781 xenografts with documented tumor burden revealed that the combination of BIBW2992 and rapamycin is the most effective treatment paradigm causing significant tumor shrinkage. Immunohistochemical analysis of lung tumors treated with BIBW2992 and rapamycin combination revealed decreased phosphorylation levels for proteins in both upstream and downstream arms of MAPK and Akt/mTOR signaling axes, indicating inhibition of these pathways. Based on these findings, clinical testing of the BIBW2992/rapamycin combination in non-small cell lung cancer patients with tumors expressing HER2 mutations is warranted.
The success of eScience research depends not only upon effective collaboration between scientists and technologists but also upon the active involvement of data archivists. Archivists rarely receive ...scientific data until findings are published, by which time important information about their origins, context, and provenance may be lost. Research reported here addresses the life cycle of data from collaborative ecological research with embedded networked sensing technologies. A better understanding of these processes will enable archivists to participate in earlier stages of the life cycle and to improve curation of these types of scientific data. Evidence from our interview study and field research yields a nine-stage life cycle. Among the findings are the cumulative effect of decisions made at each stage of the life cycle; the balance of decision-making between scientific and technology research partners; and the loss of certain types of data that may be essential to later interpretation.
In the process of scientific research, many information objects are generated, all of which may remain valuable indefinitely. However, artifacts such as instrument data and associated calibration ...information may have little value in isolation; their meaning is derived from their relationships to each other. Individual artifacts are best represented as components of a life cycle that is specific to a scientific research domain or project. Current cataloging practices do not describe objects at a sufficient level of granularity nor do they offer the globally persistent identifiers necessary to discover and manage scholarly products with World Wide Web standards. The Open Archives Initiative's Object Reuse and Exchange data model (OAI‐ORE) meets these requirements. We demonstrate a conceptual implementation of OAI‐ORE to represent the scientific life cycles of embedded networked sensor applications in seismology and environmental sciences. By establishing relationships between publications, data, and contextual research information, we illustrate how to obtain a richer and more realistic view of scientific practices. That view can facilitate new forms of scientific research and learning. Our analysis is framed by studies of scientific practices in a large, multidisciplinary, multi‐university science and engineering research center, the Center for Embedded Networked Sensing.
The success of eScience research depends not only upon effective collaboration between scientists and technologists but also upon the active involvement of data archivists. Archivists rarely receive ...scientific data until findings are published, by which time important information about their origins, context, and provenance may be lost. Research reported here addresses the life cycle of data from collaborative ecological research with embedded networked sensing technologies. A better understanding of these processes will enable archivists to participate in earlier stages of the life cycle and to improve curation of these types of scientific data. Evidence from our interview study and field research yields a nine-stage life cycle. Among the findings are the cumulative effect of decisions made at each stage of the life cycle; the balance of decision-making between scientific and technology research partners; and the loss of certain types of data that may be essential to later interpretation.
The success of eScience research depends not only upon effective collaboration between scientists and technologists but also upon the active involvement of data archivists. Archivists rarely receive ...scientific data until findings are published, by which time important information about their origins, context, and provenance may be lost. Research reported here addresses the life cycle of data from collaborative ecological research with embedded networked sensing technologies. A better understanding of these processes will enable archivists to participate in earlier stages of the life cycle and to improve curation of these types of scientific data. Evidence from our interview study and field research yields a nine-stage life cycle. Among the findings are the cumulative effect of decisions made at each stage of the life cycle; the balance of decision-making between scientific and technology research partners; and the loss of certain types of data that may be essential to later interpretation.
The success of eScience research depends not only upon effective collaboration between scientists and technologists but also upon the active involvement of data archivists. Archivists rarely receive ...scientific data until findings are published, by which time important information about their origins, context, and provenance may be lost. Research reported here addresses the life cycle of data from collaborative ecological research with embedded networked sensing technologies. A better understanding of these processes will enable archivists to participate in earlier stages of the life cycle and to improve curation of these types of scientific data. Evidence from our interview study and field research yields a nine-stage life cycle. Among the findings are the cumulative effect of decisions made at each stage of the life cycle; the balance of decision-making between scientific and technology research partners; and the loss of certain types of data that may be essential to later interpretation.
The success of eScience research depends not only upon effective collaboration between scientists and technologists but also upon the active involvement of data archivists. Archivists rarely receive ...scientific data until findings are published, by which time important information about their origins, context, and provenance may be lost. Research reported here addresses the life cycle of data from collaborative ecological research with embedded networked sensing technologies. A better understanding of these processes will enable archivists to participate in earlier stages of the life cycle and to improve curation of these types of scientific data. Evidence from our interview study and field research yields a nine-stage life cycle. Among the findings are the cumulative effect of decisions made at each stage of the life cycle; the balance of decision-making between scientific and technology research partners; and the loss of certain types of data that may be essential to later interpretation.
The success of eScience research depends not only upon effective collaboration between scientists and technologists but also upon the active involvement of data archivists. Archivists rarely receive ...scientific data until findings are published, by which time important information about their origins, context, and provenance may be lost. Research reported here addresses the life cycle of data from collaborative ecological research with embedded networked sensing technologies. A better understanding of these processes will enable archivists to participate in earlier stages of the life cycle and to improve curation of these types of scientific data. Evidence from our interview study and field research yields a nine-stage life cycle. Among the findings are the cumulative effect of decisions made at each stage of the life cycle; the balance of decision-making between scientific and technology research partners; and the loss of certain types of data that may be essential to later interpretation.
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