1,724,959 research outputs found
Block Card 5259 Norton Place
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: 5259 Norton Place (Toledo, Ohio) | Rancamp Place Addition (Toledo, Ohio) | South Toledo Area (Toledo, Ohio) | Ranch houses | Dwellin
Abstract 5259: Urolithin A prevents pancreatic tumor growth and increases survival by inhibiting PI3K/PDK1 and STAT3 signaling
No full textAbstract
Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer-related mortality in the United States. Most patients present with an advanced disease and the majority die within five years, many surviving less than six months. Cytotoxic chemotherapy including Gemcitabine (Gem), FOLFIRINOX, nab-paclitaxel offer modest improvement in survival, albeit at the cost of increased side effects and unwanted toxicities. Therefore, developing novel chemotherapeutic agents for PDAC treatment is critical to improve survival. Ellagic acid/ellatitannins are abundantly present in the pomegranate and berries, are actively metabolized by the intestinal microflora to Urolithin A (UA). Oral administration of UA has shown to be highly bioavailable and non-toxic. UA inhibits multiple kinases that are known to be involved in PDAC progression and metastasis. Therefore, we hypothesized that UA would elicit potent anti-cancer therapeutic potential in PDAC. The effect of UA on kinase activity was assessed . Inhibition of AKT (downstream of PI3K/PDK1), p70 S6 Kinase (PS6K) and STAT3 activation was quantified in PDAC cells treated with UA in dose-dependent manner. The mechanism of action was validated for UA’s activity on PI3K/PDK1, PS6K and STAT3 activation using immunoblot analysis. MiaPaCa2 cells were treated with specific inhibitors for either AKT (MK2206) or STAT3 (AZD1480) and analyzed for tumorigenicity. UA treated PDAC cells were analyzed for cell proliferation, cell invasion and colony formation. Cell cycle analysis and cell apoptosis were measured by flow cytometry. To test the efficacy of UA in vivo, cells were implanted subcutaneously in athymic nude mice. The animals received UA daily and tumor volume was measured for 5 weeks. Next, we assessed tumor growth and overall survival (OS) in PKT (Ptf1acre/+;LSL-KrasG12D;Tgfbr2fl/fl) mice, an aggressive genetically engineered PDAC mouse model, in response to UA and/or Gem treatment. Tissues from the xenografts and PKT mice treated with vehicle or UA were analyzed for cell proliferation (Ki67) and apoptosis (cleaved Caspase 3) by immunohistochemistry. High expression levels of activated STAT3 or AKT correlate with decreased survival in PDAC. UA treated MiaPaCa2 cells showed significant dose-dependent increase in apoptosis and decrease in anchorage-independent growth. UA inhibited AKT, PS6K and STAT3 signaling. As a single agent, UA effectively reduced in vivo PDAC tumor growth. Immunohistochemistry of UA treated tissues from tumor xenografts and PKT mice showed inhibition of Ki67 positive tumor cells and increased cleaved caspase 3 staining. PKT mice treated with UA showed a decrease in tumor size and an increased OS when compared to vehicle or Gem treated mice alone. These findings show that UA is a novel inhibitor/modulator/regulator for multiple signaling pathways in PDAC. These results suggest UA has potential for pre-clinical development in pancreatic cancer.
Citation Format: Supriya Srinivasan, Venkatakrishna Jala, Kumar Honnenahally, Jason Castellanos, Praveen Kumar Vermula, Michael VanSaun, Nipun Merchant, Nagaraj Nagathihalli. Urolithin A prevents pancreatic tumor growth and increases survival by inhibiting PI3K/PDK1 and STAT3 signaling [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 5259. doi:10.1158/1538-7445.AM2017-5259</jats:p
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
The Miyake-Hawthorne Consilience - A Unifying Forensic Reconstruction of Global Plasma Catastrophies (5259 BCE, 663 BCE)
No full textThe Miyake-Hawthorne Consilience - A Unifying Forensic Reconstruction of Global Plasma Catastrophies (5259 BCE, 663 BCE)
Subject: A Proposed Transdisciplinary Absolute Chronology Linking High-Energy Solar Particle Events (SPE) to East Asian Cultural Foundations and Archaeological Type-Specimens.
1. Scientific Objective
To establish a "Golden Spike" absolute chronology for East Asian Neolithic and Iron Age sites by correlating known Miyake Events (specifically 5259 BCE and 663 BCE) with high-resolution archaeological markers and indigenous record-keeping.
2. Core Hypothesis
This research proposes that the 663 BCE Miyake Event-a verified global radiocarbon excursion-is the physical catalyst for the Japanese Yatagarasu (Eight-Span Crow) phenomenon. In fact, according to the Nihon Shoki, 663 was the "pivotal" year. It was during this year in the treacherous crossing of the Kumano mountains that the Yatagarasu appeared to lead Jimmu's disoriented army through the peaks. The 3-year alignment with the traditional founding of Japan (660 BCE) suggests that the "Sun-Bird" was a real-time observation of a massive solar proton event/plasma burst, subsequently encoded into the state's "Cosmic Authority." Therefore the author would like to take this time to honor Dr. Miyake's efforts by naming this Solar Particle Event (SPE), "The Yatagarasu Miyake Event of 663 BCE".
3. Data Correlation & "The Consilience of Proof"
Physical Evidence:
Dendrochronological: 18O and 14C spikes identified by Dr. Fusa Miyake et al. in Japanese master chronologies (e.g., the 4354-year-long central Japan record).
Glaciological: 10Be and 36Cl ice core samples verify the 663 BCE Solar Particle Event and dendrochronological records.
Archaeological Markers: The absolute dating of wooden pillars (Itazuke/Yayoi sites) to the 663 ВСЕ event, mirroring the success of the 5259 BCE absolute dating of the Dispilio Tablet in Europe.
Cultural Record: Chronologically verified by the Nihon Shoki. First the poisonous cloud that caused Jimmu's army to fall asleep. Telluric currents induced for the passing charged particles in the CME superheated the local hot springs causing steam with higher concentrations of hydrogen sulfide. Finally the transition from the "Eight-Span Crow" (visual observation) to the "Three-Legged Crow" (systemic Yangshou 5480, 5410, or 5259 BCE/Chinese philosophical update) as a record of high-frequency solar activity.
4. Falsifiable Prediction
I predict that conical amphoras from the Yangshao/Majiayao cultures (displaying "Sun-Bird" and "Halo" motifs) will return a single-year absolute date of 5259 BCE (or within the 5480-5259 BCE cluster) when subjected to the Dispilio-style radiocarbon wiggle-matching protocol.
5. Conclusion & Tribute
By naming this the "Yatagarasu-Miyake Event," this study seeks to honor the pioneering dendrochronological work of Dr. Fusa Miyake while validating the precision of Japanese, Chinese, and Korean observations of solar phenomena. This synthesis acknowledges the shared celestial heritage of the Sanzuwu (China), Samjogo (Korea), and Yatagarasu (Japan) as a unified record of Earth's interaction with the Sun
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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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