1,721,035 research outputs found
Abstract 1231: Restoration of tumor suppression <i>in vivo</i> by systemic delivery of PTEN mRNA nanoparticles
No full textAbstract
PTEN (phosphatase and tensin homolog on chromosome ten) is one of the most common lost or mutated tumor suppressor genes in human cancers, including ~50% of metastatic castration-resistant prostate cancer (mCRPC). By catalyzing PIP3 dephosphorylation, PTEN negatively regulates the PI3K-AKT-mTOR pathway, which is frequently altered in mCRPC. Reintroduction of functional PTEN for mCRPC treatment has proven difficult. By employing self-assembled lipid-polymer hybrid nanoparticle platforms, we successfully reintroduced PTEN mRNA to PTEN-null prostate cancer cells both in vitro and in vivo. These mRNA-loaded nanoparticles demonstrate high protein expression efficiency, low toxicity and good stability in serum and tumor accumulation. We confirmed that restoration of PTEN in PTEN-null prostate cancer cells inhibits the PI3k-AKT pathway, reduces cell viability and enhances apoptosis in vitro. Systemic delivery of PTEN mRNA-loaded nanoparticles in prostate xenograft tumors results in ~85% inhibition of tumor growth and leads to tumor cell death without toxic side effects in vivo. In summary, this work provides proof of concept of mRNA-based gene therapy for systemic restoration of functional PTEN for tumor suppression in vivo. It represents a novel approach to PI3K-AKT pathway inhibition, with the potential to specifically target cancers with loss of PTEN function.
Citation Format: Yingjie Xu, Mohammad Ariful Islam, Harshal Zope, Morteza Mahmoudi, Robert S. Langer, Jinjun Shi, Bruce R. Zetter, Omid C. Farokhzad. Restoration of tumor suppression in vivo by systemic delivery of PTEN mRNA nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1231. doi:10.1158/1538-7445.AM2017-1231</jats:p
バングラデシュにおける稲作の近代技術が生産効率性と厚生におよぼす影響に関する経済学的研究
Get PDF京都大学0048新制・課程博士博士(農学)甲第20716号農博第2245号新制||農||1053(附属図書館)学位論文||H29||N5082(農学部図書室)京都大学大学院農学研究科生物資源経済学専攻(主査)教授 福井 清一, 教授 伊藤 順一, 教授 梅津 千恵子学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDGA
Design and development of an application to collect data from an Intelligent Information Management system
No full textWhen software is released, it is common that the end-user will discover some issues while using the software. Issues can occur due to the software itself, data managed by the software, configurations, integrations, or the underlying environment. For investigating these issues properly, data from the end user's environment is important. No software developer or support engineer can fix issues on the fly without having proper information on the system having the issues and knowing the use case scenario. Often the issue is that it is not outright clear which data is needed and which data is not. If the correct data is not gathered outright, resolving the issue will take a long time as more data needs to be collected later. If all the possible data is collected immediately, a lot of time and work that is not necessary may be needed to collect that data. Collecting the data may also require following lengthy instructions, and sometimes those instructions can be software version specific. Besides, it is always possible that provided information is incorrect or incomplete, which causes extra work for support engineer or developer responsible in order to debug the issue. To ensure proper information is passed to the concerned team, having a tool to collect necessary logs automatically from the system is a convenient and trustworthy way.
Customers usually send required information and logs through the ticketing tool or other interactive means. Occasionally the provided data may be inaccurate, some requested data may be omitted, and in some cases, the data might be even incorrect. It is a problem for the responsible support teams to resolve issues when the client delivers the wrong data. The primary objective of this thesis study is to collect requirements for an application that could automatize many of the data collection tasks and then design and implement a proof of concept version of such a tool. The number of requirements may be so high that implementing all of them may not be possible within the scope of this thesis. Hence the proof of concept version should have a reasonable subset of those requirements and have modularity to add new requirements later. The tool must also consider factors like performance, so that the application may use multithreading where feasible. Additionally, other factors like privacy and visibility of data collection should be considered. Requirements that cannot be fulfilled due to issues like technical limitations or performance can be omitted. However, features that can be implemented in the future should be considered in the architectural design of the tool.
Based on the objectives of the study, three research questions were set, and answering these questions would benefit both academics and industry. The implementation requirements were collected based on the responses from the responsible parties. Depending on the decisions on the subset of the gathered requirements, goals were set for the study. Moreover, the proof of concept version of the software was designed and implemented fully. During the trial run, it is found that the application may help to reduce the required time and effort for gathering the required data in comparison with the manual data collection process. From the result of the study, it is proven that having such a tool to gather required information and logs on the M-Files system is a practical track to pursue. This developed application may result in a valuable part of M-Files software in the future. Through the initial implementation and deployment of the application can result in a short time loss of resources but will benefit in a longer run
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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