bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visitor Behavior and Experiences in the Four Permanent Galleries at The Tech Museum of Innovation
Authors: Korn Randi , Jones Johanna 
Published: May 2010

ABSTRACTThis article presents a few salient findings from Phase I of an evaluation conducted at The Tech Museum of Innovation. Phase I focused on articulating visitors' behaviors and experiences in each of the four permanent galleries. Observations showed that visitors are spending about the same amount of time in the galleries as they spend in other museums' nondiorama exhibits, but they visit fewer components. Because some galleries performed better than others, this manuscript provides a rationale for the range of behavioral data by examining behaviors at various component types. In‐depth interviews provide another perspective on the visitor experience. They showed that in some cases visitors are not grasping the individual messages of the galleries. Observation data suggest why visitors failed to obtain the galleries' big ideas. The challenge for The Tech is to consider the unique behaviors that the exhibits promote and to rework their exhibits so they more strongly reflect and convey each gallery's big idea.
Ten Years of Evaluating Science Theater at the Museum of Science, Boston
Authors: BAUM LYNN , HUGHES CATHERINE 
Published: May 2010

ABSTRACTThis paper is a meta‐analysis of a series of theatre program evaluations carried out at the Museum of Science in Boston, Massachusetts over ten years. The evaluations, conducted independently of each other, had varying goals and used a range of methodologies. Nonetheless, looked at together, the aggregate results of these evaluations reflect a compelling, positive theatre experience for visitors. There is collective evidence of cognitive gain for visitors attending performances. In summary, the overview of ten years of evaluations portrays theater as a successful format for communicating information and ideas on many levels, which visitors enjoy and remember. Much remains to be learned about the effectiveness and impact of theater in museums. It is the intention of this paper to use the collective results of these studies as a foundation, and to move the conversation from basic evaluation to further research examining the learning potential of this medium in greater depth.
From Period Rooms to Public Trust: The Authority Debate and Art Museum Leadership in America
Authors: DUNCAN SALLY ANNE 
Published: May 2010

ABSTRACTA recent lecture series at the Harvard University Art Museums titled “Art Museums and the Public Trust” marked the eightieth anniversary of the founding of Harvard's famed Museum Course. A graduate seminar begun in 1921 by the Fogg Art Museum's associate director, Paul J. Sachs, the Museum Course became the primary training ground for art museum leadership in the first half of the twentieth century. The 2001 commemorative lecture series was intended to foster a healthy debate on the place of the art museum in Anglo‐American culture. Instead, the speakers, veteran directors of America's and England's most prestigious art museums, invariably returned to one concern: authority—theirs and that of the art museum itself in contemporary society. Authority was at the heart of the Museum Course decades earlier, tellingly explored in annual debates around two significant topics. The first debate involved the pros and cons of including period rooms in American museums. In the second, students argued about whether America's established art institutions should collect the work of living artists. Questions of how museums should respond to the interests of audiences and communities, their responsibility to contemporary artists, and the meaning of a public trust trouble America's museum leadership now as then. This article explores the common ground between the Museum Course debates of the 1930s and Harvard's recent commemorative “debates” by America's contemporary museum leaders and comments on its significance for today's museums.
Diagnostic utility of glypican-3 for hepatocellular carcinoma on liver needle biopsy
Authors: Wang Feng Hua , Yip Yuk Ching , Zhang Meng , Vong Heong Ting , Chan Kin Iong , Wai Kit Cheng , Wen Jian Ming 
Published: May 2010

AimsGlypican 3 (GPC3) is a heparan sulphate proteoglycan that shows elevated levels in the serum of patients with hepatocellular carcinoma (HCC), but not in healthy blood donors or patients with benign liver disease. This study explores the value of GPC3 expression for diagnosis of HCC by immunohistochemistry in liver needle biopsy specimens.MethodsArchival material of liver needle biopsies from 54 patients with HCC, nine with focal nodular hyperplasia or focal liver cell dysplasia, five with cirrhosis, seven with hepatitis B or unremarkable liver tissue, seven with cholangiocarcinoma, and 30 with metastatic tumours, was retrieved for immunohistochemical staining with GPC3 antibody and appropriate positive and negative controls.ResultsForty-five out of 54 cases of HCC showed positive GPC3 staining (83.4%). In contrast, all 58 non-HCC cases of liver biopsies, including focal nodular hyperplasia, focal liver cell dysplasia, cirrhosis, hepatitis B or unremarkable liver tissue, cholangiocarcinoma and metastatic tumours, were negative for GPC3. The sensitivity and specificity of GPC3 in HCCs were 83.4% and 100%, respectively.ConclusionsGPC3 is a valuable diagnostic marker for diagnosing HCC on liver needle biopsy. It can be used to distinguish HCC from other benign hepatic conditions and metastatic tumours in the liver.
Genetic population structure of broad whitefish, Coregonus nasus, from the Mackenzie River, Northwest Territories: implications for subsistence fishery management
Authors: Harris Les N. , Taylor Eric B. 
Published: May 2010

We assayed microsatellite DNA variation among 1013 broad whitefish, Coregonus nasus , from 36 localities within the lower Mackenzie River (Northwest Territories, Canada) to provide the first assessment of fine-scale population structuring of broad whitefish in this large system. Among sampling locations, averaged across all loci, the number of alleles ranged from 3.00 to 6.71 and heterozygosity averaged 0.54. Population subdivision was generally low, but significant (θ = 0.026, P < 0.05), although pairwise comparisons indicated that overall significance was heavily influenced by comparisons between anadromous and lacustrine groups. Bayesian-based STRUCTURE analysis suggested that there are two main genetic groups within our study area: anadromous and lacustrine broad whitefish. A mixture analysis indicated that all populations contribute to the lower Mackenzie River subsistence fishery, yet catches were dominated by Peel River fish, highlighting the importance of this tributary. Our data also supported the idea that there are several units of conservation among Mackenzie River system broad whitefish populations and that management strategies should be implemented accordingly.
Mantle cavity water oxygen partial pressure (Po2) in marine molluscs aligns with lifestyle
Authors: Abele Doris , Kruppe Melanie , Philipp Eva E. R. , Brey Thomas 
Published: May 2010

Marine invertebrates with open circulatory system establish low and constant oxygen partial pressure (Po2) around their tissues. We hypothesized that as a first step towards maintenance of low haemolymph and tissue oxygenation, the Po2in molluscan mantle cavity water should be lowered against normoxic (21 kPa) seawater Po2, but balanced high enough to meet the energetic requirements in a given species. We recorded Po2in mantle cavity water of five molluscan species with different lifestyles, two pectinids ( Aequipecten opercularis , Pecten maximus ), two mud clams ( Arctica islandica , Mya arenaria ), and a limpet ( Patella vulgata ). All species maintain mantle cavity water oxygenation below normoxic Po2. Average mantle cavity water Po2correlates positively with standard metabolic rate (SMR): highest in scallops and lowest in mud clams. Scallops show typical Po2frequency distribution, with peaks between 3 and 10 kPa, whereas mud clams and limpets maintain mantle water Po2mostly <5 kPa. Only A. islandica and P. vulgata display distinguishable temporal patterns in Po2time series. Adjustment of mantle cavity Po2to lower than ambient levels through controlled pumping prevents high oxygen gradients between bivalve tissues and surrounding fluid, limiting oxygen flux across the body surface. The patterns of Po2in mantle cavity water correspond to molluscan ecotypes.
Population estimation of bocaccio (Sebastes paucispinis) based on larval production
Authors: Ralston Stephen , MacFarlane Bruce R. 
Published: May 2010

We estimate the stock size of bocaccio ( Sebastes paucispinis ) in the Southern California Bight based on the production of larvae. Area-weighted total length compositions of preflexion larvae in 2002 and 2003 were determined from ichthyoplankton survey data. Larval length-to-age transition matrices were estimated from data derived from the enumeration of daily otolith increments. In combination, these results were used to estimate daily rates of larval production and mortality during surveys conducted in those years. Daily rates of larval production were expanded to annual production rates using information developed from the long-term seasonal distribution of larvae in CalCOFI surveys. Total annual larval production was translated to total spawning biomass by calculation of the female population weight-specific fecundity derived from a length-based life table analysis of adult reproductive parameters. Our results indicate that there were 6953 – 10 656 metric tons of bocaccio biomass (males and females >16 cm fork length) in the Southern California Bight during the survey years, which agrees with biomass estimates from a traditional stock assessment. Unique and problematic aspects of the reproductive biology of Sebastes are discussed, including multiple spawning, weight-specific fecundity that depends on size, and bias in fecundity data gathered from vitellogenic ovaries.
Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer
Authors: Pond Adam C. , Herschkowitz Jason I. , Schwertfeger Kathryn L. , Welm Bryan , Zhang Yiqun , York Brian , Cardiff Robert D. , Hilsenbeck Susan , Perou Charles M. , Creighton Chad J. , Lloyd Richard E. , Rosen Jeffrey M. 
Published: May 2010

Abstract
Fibroblast growth factor (FGF) cooperates with the Wnt/β-catenin pathway to promote mammary tumorigenesis. To investigate the mechanisms involved in FGF/Wnt cooperation, we genetically engineered a model of inducible FGF receptor (iFGFR) signaling in the context of the well-established mouse mammary tumor virus–Wnt-1 transgenic mouse. In the bigenic mice, iFGFR1 activation dramatically enhanced mammary tumorigenesis. Expression microarray analysis did not show transcriptional enhancement of Wnt/β-catenin target genes but instead showed a translational gene signature that also correlated with elevated FGFR1 and FGFR2 in human breast cancer data sets. Additionally, iFGFR1 activation enhanced recruitment of RNA to polysomes, resulting in a marked increase in protein expression of several different Wnt/β-catenin target genes. FGF pathway activation stimulated extracellular signal-regulated kinase and the phosphorylation of key translation regulators both in vivo in the mouse model and in vitro in a human breast cancer cell line. Our results suggest that cooperation of the FGF and Wnt pathways in mammary tumorigenesis is based on the activation of protein translational pathways that result in, but are not limited to, increased expression of Wnt/β-catenin target genes (at the level of protein translation). Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling. Cancer Res; 70(12); 4868–79. ©2010 AACR.
MiR-199a-3p Regulates mTOR and c-Met to Influence the Doxorubicin Sensitivity of Human Hepatocarcinoma Cells
Authors: Fornari Francesca , Milazzo Maddalena , Chieco Pasquale , Negrini Massimo , Calin George Adrian , Grazi Gian Luca , Pollutri Daniela , Croce Carlo Maria , Bolondi Luigi , Gramantieri Laura 
Published: May 2010

Abstract
MicroRNAs (miRNA) have rapidly emerged as modulators of gene expression in cancer in which they may have great diagnostic and therapeutic import. MicroRNA-199a-3p (miR-199a-3p) is downregulated in several human malignancies including hepatocellular carcinoma (HCC). Here, we show that miR-199a-3p targets mammalian target of rapamycin (mTOR) and c-Met in HCC cells. Restoring attenuated levels of miR-199a-3p in HCC cells led to G1-phase cell cycle arrest, reduced invasive capability, enhanced susceptibility to hypoxia, and increased sensitivity to doxorubicin-induced apoptosis. These in vitro findings were confirmed by an analysis of human HCC tissues, which revealed an inverse correlation linking miR-199a-3p and mTOR as well as a shorter time to recurrence after HCC resection in patients with lower miR-199a-3p expression. These results suggest that tactics to regulate mTOR and c-Met by elevating levels of miR-199a-3p may have therapeutic benefits in highly lethal cancers such as HCC. Cancer Res; 70(12); 5184–93. ©2010 AACR.
A Dominant Mutant Allele of the ING4 Tumor Suppressor Found in Human Cancer Cells Exacerbates MYC-Initiated Mouse Mammary Tumorigenesis
Authors: Kim Suwon , Welm Alana L. , Bishop J. Michael 
Published: May 2010

Abstract
ING4 is a candidate tumor suppressor gene that is deleted in 10% to 20% of human breast cancers and is mutated in various human cancer cell lines. To evaluate whether ING4 has a tumor-suppressive role in breast tissue, we overexpressed it in mouse mammary glands using a transplant system. Ectopic expression of ING4 suppressed MYC-induced mammary hyperplasia, but not tumorigenesis. In the same model system, we show that a COOH-terminal truncation mutant of ING4 found in human cancer cells could act alone to induce abnormal gland structures resembling mammary hyperplasia, which did not progress to tumors. However, coexpression of the ING4 mutant with MYC increased the penetrance and metastasis of MYC-initiated mammary tumors, giving rise to tumors with more organized acinar structures. Similarly, in vitro expression of the ING4 mutant in MCF10A mammary epithelial cells reinforced tight junctional structures. Our results provide direct functional evidence that ING4 could suppress the early stages of breast cancer and that dominant mutant alleles of ING4 might contribute to malignant development. Cancer Res; 70(12); 5155–62. ©2010 AACR.
Cbl and Human Myeloid Neoplasms: The Cbl Oncogene Comes of Age
Authors: Kales Stephen C. , Ryan Philip E. , Nau Marion M. , Lipkowitz Stanley 
Published: May 2010

Abstract
Cbl was originally discovered in 1989 as the cellular homolog of the v-Cbl oncogene, the transforming gene of the Cas NS-1 murine retrovirus that causes myeloid leukemia and lymphomas in mice. Cbl is a member of a family of RING finger ubiquitin ligases that negatively regulate signaling by tyrosine kinases and that function as adaptor proteins to regulate signaling positively. Until the past 2 years, there was little evidence that Cbl proteins were involved in human malignancies. Recent publications have shown homozygous mutations in Cbl in human myeloid neoplasms. Although in vitro and animal transformation models suggested that mutant forms of Cbl acted as an oncogene, the cellular role suggested that the protein could serve as a tumor suppressor gene. The recent data begin to reconcile this paradox as the loss of ubiquitin ligase function (the tumor suppressor function) is coupled to the maintenance of the positive signaling function (the oncogene function). These data also provide insight into potential therapeutic approaches to myeloid disorders harboring Cbl mutations. Cancer Res; 70(12); 4789–94. ©2010 AACR.
Angiopoietin-2 Interferes with Anti-VEGFR2–Induced Vessel Normalization and Survival Benefit in Mice Bearing Gliomas
Authors: Chae Sung-Suk , Kamoun Walid S. , Farrar Christian T. , Kirkpatrick Nathaniel D. , Niemeyer Elisabeth , de Graaf Annemarie M.A. , Sorensen A. Gregory , Munn Lance L. , Jain Rakesh K. , Fukumura Dai 
Published: May 2010

Abstract
Purpose: In brain tumors, cerebral edema is a significant source of morbidity and mortality. Recent studies have shown that inhibition of vascular endothelial growth factor (VEGF) signaling induces transient vascular normalization and reduces cerebral edema, resulting in a modest survival benefit in glioblastoma patients. During anti-VEGF treatment, circulating levels of angiopoietin (Ang)-2 remained high after an initial minor reduction. It is not known, however, whether Ang-2 can modulate anti-VEGF treatment of glioblastoma. Here, we used an orthotopic glioma model to test the hypothesis that Ang-2 is an additional target for improving the efficacy of current anti-VEGF therapies in glioma patients.
Experimental Design: To recapitulate high levels of Ang-2 in glioblastoma patients during anti-VEGF treatment, Ang-2 was ectopically expressed in U87 glioma cells. Animal survival and tumor growth were assessed to determine the effects of Ang-2 and anti–VEGF receptor 2 (VEGFR2) treatment. We also monitored morphologic and functional vascular changes using multiphoton laser scanning microscopy and immunohistochemistry.
Results: Ectopic expression of Ang-2 had no effect on vascular permeability, tumor growth, or survival, although it resulted in higher vascular density, with dilated vessels and reduced mural cell coverage. On the other hand, when combined with anti-VEGFR2 treatment, Ang-2 destabilized vessels without affecting vessel regression and compromised the survival benefit of VEGFR2 inhibition by increasing vascular permeability. VEGFR2 inhibition normalized tumor vasculature whereas ectopic expression of Ang-2 diminished the beneficial effects of VEGFR2 blockade by inhibiting vessel normalization.
Conclusion: Cancer treatment regimens combining anti-VEGF and anti-Ang-2 agents may be an effective strategy to improve the efficacy of current anti-VEGF therapies. Clin Cancer Res; 16(14); 3618–27. ©2010 AACR.
Development of Autoantibody Signatures as Novel Diagnostic Biomarkers of Non–Small Cell Lung Cancer
Authors: Wu Lingling , Chang Wenjun , Zhao Jinfeng , Yu Yongwei , Tan Xiaojie , Su Tong , Zhao Lijun , Huang Shengdong , Liu Shiyuan , Cao Guangwen 
Published: May 2010

Abstract
Purpose: To select autoantibody signatures as noninvasive biomarkers of non–small cell lung cancer (NSCLC).
Experimental Design: A phage cDNA expression library was constructed with fresh samples from 30 lung cancer patients and biopanned using serum pools of 10 NSCLC patients and 10 healthy controls. A six–phage peptide detector was discovered by two-step immunoscreenings and was validated in an independent set of 90 NSCLC patients and 90 matched healthy controls, 30 NSCLC patients with chemotherapy, and 12 chronic obstructive pulmonary disease (COPD) patients. The expression of a peptide target was validated by using immunohistochemistry. Factors affecting NSCLC-related death were evaluated by Cox regression analysis.
Results: Six phage peptide clones showing higher seroreactivity than others in 30 NSCLC patients were selected for diagnostic validation. The six–phage peptide detector was able to discriminate between NSCLC patients and healthy controls with a sensitivity and specificity of &gt;92%, and had similar validity for indicating NSCLC at early stage. The seroreactivity of the six phage peptides was significantly higher in the NSCLC patients than in those with chemotherapy and the COPD patients, respectively. Of the six phage peptides, one encoded a peptide showing 100% homology to olfactomedin 1. Expression of olfactomedin 1 protein was significantly higher in lung adenocarcinoma than in lung cancer of other histologic types and normal lung tissues. The autoantibody signature was not associated with the prognosis of the NSCLC patients.
Conclusions: The six–phage peptide detector stands out as promising diagnostic biomarkers for NSCLC, unlikely for NSCLC relapse after chemotherapy. Olfactomedin 1 may be a novel target of lung adenocarcinoma. Clin Cancer Res; 16(14); 3760–8. ©2010 AACR.
Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib
Authors: O'Brien Neil A. , Browne Brigid C. , Chow Lucy , Wang Yuhua , Ginther Charles , Arboleda Jane , Duffy Michael J. , Crown John , O'Donovan Norma , Slamon Dennis J. 
Published: May 2010

Abstract
Trastuzumab and lapatinib provide clinical benefit to women with human epidermal growth factor receptor 2 (HER)–positive breast cancer. However, not all patients whose tumors contain the HER2 alteration respond. Consequently, there is an urgent need to identify new predictive factors for these agents. The aim of this study was to investigate the role of receptor tyrosine kinase signaling and phosphoinositide 3-kinase (PI3K)/AKT pathway activation in conferring resistance to trastuzumab and lapatinib. To address this question, we evaluated response to trastuzumab and lapatinib in a panel of 18 HER2-amplified cell lines, using both two- and three-dimensional culture. The SUM-225, HCC-1419, HCC-1954, UACC-893, HCC-1569, UACC-732, JIMT-1, and MDA-453 cell lines were found to be innately resistant to trastuzumab, whereas the MDA-361, MDA-453, HCC-1569, UACC-732, JIMT-1, HCC-202, and UACC-893 cells are innately lapatinib resistant. Lapatinib was active in de novo (SUM-225, HCC-1419, and HCC-1954) and in a BT-474 cell line with acquired resistance to trastuzumab. In these cells, trastuzumab had little effect on AKT phosphorylation, whereas lapatinib retained activity through the dephosphorylation of AKT. Increased phosphorylation of HER2, epidermal growth factor receptor, HER3, and insulin-like growth factor IR correlated with response to lapatinib but not trastuzumab. Loss of PTEN or the presence of activating mutations in PI3K marked resistance to trastuzumab, but lapatinib response was independent of these factors. Thus, increased activation of the PI3K/AKT pathway correlates with resistance to trastuzumab, which can be overcome by lapatinib. In conclusion, pharmacologic targeting of the PI3K/AKT pathway may provide benefit to HER2-positive breast cancer patients who are resistant to trastuzumab therapy. Mol Cancer Ther; 9(6); 1489–502. ©2010 AACR.
Oligodeoxyribozymes That Cleave β-Catenin Messenger RNA Inhibit Growth of Colon Cancer Cells via Reduction of β-Catenin Response Transcription
Authors: Choi Bo-Ra , Gwak Jungsug , Kwon Hyun-Mi , Oh Sangtaek , Kim Kwang Pyo , Choi Woo-Hyung , Cho Yo-Han , Kim Dong-Eun 
Published: May 2010

Abstract
Abnormal regulation of Wnt/β-catenin signaling followed by increased levels of the β-catenin protein have been identified in enhanced cellular proliferation and development of colon polyps and cancers. To inhibit β-catenin gene expression in colon cancer cells, RNA-cleaving oligodeoxyribozyme (DNAzyme) was employed to destroy the β-catenin mRNA. We designed a strategy to identify the cleavage sites in β-catenin RNA with a pool of random sequences from a DNAzyme library and identified four potential DNAzyme-working sites. DNAzymes were constructed for the selected target sites and were tested for the ability to cleave β-catenin RNA. When introduced into the cells, the selected DNAzymes decreased the expression of β-catenin significantly as well as its downstream gene, cyclin D1. Additionally, we designed short hairpin RNA that targets the same cleavage site for the selected DNAzyme. The designed short hairpin RNA also inhibited β-catenin gene expression in colon cancer cells. Our studies show that RNA-cleaving DNAzymes and RNA interference targeted to β-catenin significantly reduced β-catenin–dependent gene expression, resulting in inhibition of colon cancer cell growth. These results indicate that the functional antisense oligonucleotides directed against β-catenin might have potential as a therapeutic intervention to treat colon cancer. Mol Cancer Ther; 9(6); 1894–902. ©2010 AACR.