bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Science Career Ladder at the New York Hall of Science
Authors: SIEGEL ERIC 
Published: May 2010

AbstractThe Science Career Ladder at the New York Hall of Science is a program that engages young people in a hierarchy of paid and unpaid experiences in the museum, designed to cultivate their interest in science and in pursuing science professions. Its double objective is to create a cadre of eloquent, well‐informed Explainers for the Hall's visitors, and to encourage underrepresented young people into science careers. This article will briefly present the history of the Science Career Ladder, describe how it currently operates, and address the challenges for sustaining the Career Ladder during a period of rapid growth.
Images of Native Americans
Authors: DOERING ZAHAVA D. , DIGIACOMO KERRY R. , PEKARIK ANDREW J. 
Published: May 2010

ABSTRACTThis article summarizes a background study conducted for museum staff planning the National Museum of the American Indian on the National Mall in Washington, DC. Through interviews we identified attitudes of Smithsonian visitors toward Native Americans. Three results stand out: First, although most visitors have had some minimal contact with contemporary Native Americans, imagery of the past dominated their responses. This past is characterized as a period in which Native Americans had freedom of movement, had control over their destiny, and lived in harmony with nature. This peaceful existence was destroyed with the arrival of the Europeans. Second, current Indian life is seen as grim, except in those cases where Native Americans have fully assimilated into urban environments. Implicit is an assumption that traditional life and values can only be maintained on reservations. At the same time, reservations are associated with poverty, alcoholism, unemployment, and poor health care. Third, visitors would like the new museum to emphasize aspects of Native life and culture that are unique or different from their own. Overall, visitors have only a cursory familiarity with Native philosophy, history, or current conditions. Very few express strongly held beliefs or positions about Native Americans.
An Effective Teacher Institute for Curriculum Dissemination1
Authors: CHASE VALERIE C. , BOONE WILLIAM J. 
Published: May 2010

ABSTRACTThis article recounts the development of Living in Water, a science curriculum for the middle grades, and the teacher training institute that was developed to disseminate the curriculum. This article also reviews how the teacher training institute was modified in response to findings from the evaluations of each of the three institutes that the authors presented. The evaluations included analysis of the teacher training institutes, the attitudes of the master teachers, the attitudes of the in‐service workshop participants, and the demographics of the students who ultimately were taught using the Living in Water curriculum.
Project Math‐Muse: Interactive Mathematics Exhibits for Young Children
Authors: GUBERMAN STEVEN R. , FLEXER ROBERTA J. , FLEXER ABRAHAM S. , TOPPING CAROLYN L. 
Published: May 2010

ABSTRACTThis paper describes the goals and preliminary work of Project Math‐Muse, an interdisciplinary team of university and public school educators working with children's museums to design and evaluate interactive mathematics exhibits for young children. Authors discuss the rationale for the development of small, interactive mathematics exhibits for young children, based on the goal of matching (a) reform‐based views of mathematics, which emphasize children's active, hands‐on engagement in meaningful activities, with (b) the principles that guide children's museums. Observations of children and adults interacting with two exhibit prototypes developed at a local children's museum are presented along with discussions of some of the issues that have arisen in this work so far. The paper concludes with directions for continued work.
Artifact Questions: Exhibiting Thought‐Provoking Objects
Authors: BERNEY ADRIENNE 
Published: May 2010

ABSTRACTA photograph in the Louisiana State Museum collection raises many questions. The image compels a viewer to ponder the circumstances associated with the creation of the portrait circa 1860, and its subsequent defacement. The piece inspired staff members to conduct a survey to assess the photograph's potential for exhibition. Survey participants interpreted the image in a variety of ways. While the majority assumed a filial relationship between the portrait's two subjects, a significant minority concluded that the picture showed a slave nanny with her White infant charge, a history that the piece's fragmented provenance supports. Most participants found the cut out face of the adult subject intriguing, and their responses suggested the power the photograph could have in an exhibition and the value of artifact questions.
Enteropathic histopathological features may be associated with Shwachman–Diamond syndrome: Figure 1
Authors: Shah N , Cambrook H , Koglmeier J , Mason C , Ancliff P , Lindley K , Smith V V , Bajaj-Elliott M , Sebire N J 
Published: May 2010

AimTo review the gastrointestinal mucosal histological features of biopsies from children with Shwachman–Diamond syndrome (SDS) examined at a single specialist centre.MethodsSearch of a clinical database was performed to identify SDS cases and their gastrointestinal biopsies were reviewed for morphological parameters such as crypt:villous ratio, crypt hyperplasia and abnormal inflammatory infiltrates. Histological sections were also immunostained with CD4, CD20 and HLA-DR to determine the nature of the inflammatory infiltrate.Results15 SDS cases were included, 7 (47%) of which showed morphologically normal duodenal villous architecture, whereas 8 (53%) showed varying degrees of enteropathic histological features ranging from villous blunting to partial villous atrophy and duodenitis. 11/15 (73%) showed some degree of duodenal inflammation, including increased lamina propria density of plasma cells, macrophages and eosinophils.ConclusionVarying degrees of duodenal inflammatory enteropathic features are present in more than 50% of symptomatic children with SDS. This suggests that, in addition to pure pancreatic exocrine failure, an enteropathic component may contribute to symptoms in some cases, and be potentially responsive to appropriate therapy.
Plasma Fibronectin Promotes Lung Metastasis by Contributions to Fibrin Clots and Tumor Cell Invasion
Authors: Malik Gunjan , Knowles Lynn M. , Dhir Rajiv , Xu Shuping , Yang Shuting , Ruoslahti Erkki , Pilch Jan 
Published: May 2010

AbstractThe attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating plasma fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin αvβ3. In vitro studies showed that fibrin-fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-fibronectin complexes to induce the activation of integrin αvβ3. Our findings reveal an important contribution of plasma fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a fibronectin-αvβ3 integrin axis, in which plasma fibronectin has to be incorporated into the blood clot. Cancer Res; 70(11); 4327–34. ©2010 AACR.
Strain-Specific Susceptibility for Pulmonary Metastasis of Sarcoma 180 Cells in Inbred Mice
Authors: Vikis Haris G. , Jackson Erin N. , Krupnick Alexander S. , Franklin Andrew , Gelman Andrew E. , Chen Qiong , Piwnica-Worms David , You Ming 
Published: May 2010

Abstract
Most cancer deaths are a result of metastasis. To extend our understanding of the factors that influence the process, we aimed to develop a mouse model of pulmonary metastasis that can be assayed in multiple inbred mouse strains for further use in identification of host genetic variants that influence metastasis. We used i.v. injection of Sarcoma 180 (S180) cells, which can be tracked and quantified by bioluminescence imaging. We observed growth of S180 cells solely in the lung and observed a wide range of pulmonary metastasis among inbred mouse strains. Interestingly, we noted that the BTBRT+tf/J strain exhibited complete clearance and provide evidence that the mechanism of resistance may involve immune factors, as strains subjected to whole-body irradiation are significantly more susceptible to tumor growth. One possible mechanism of resistance to pulmonary metastasis in BTBRT+tf/J mice may require T-cell function. Our experiments present a new mouse model for further characterization of the genetics and mechanisms of pulmonary metastasis. Cancer Res; 70(12); 4859–67. ©2010 AACR.
Genome-Wide Mapping of Estrogen Receptor-β–Binding Regions Reveals Extensive Cross-Talk with Transcription Factor Activator Protein-1
Authors: Zhao Chunyan , Gao Hui , Liu Yawen , Papoutsi Zoi , Jaffrey Sadaf , Gustafsson Jan-Åke , Dahlman-Wright Karin 
Published: May 2010

Abstract
Estrogen signaling can occur through a nonclassical pathway involving the interaction of estrogen receptors (ER) with other transcription factors such as activator protein-1 (AP-1) and SP-1. However, there is little mechanistic understanding about this pathway, with conflicting results from in vitro investigations. In this study, we applied the ChIP-on-chip approach to identify ERβ-binding sites on a genome-wide scale, identifying 1,457 high-confidence binding sites in ERβ-overexpressing MCF7 breast cancer cells. Genes containing ERβ-binding sites can be regulated by E2. Notably, ∼60% of the genomic regions bound by ERβ contained AP-1–like binding regions and estrogen response element–like sites, suggesting a functional association between AP-1 and ERβ signaling. Chromatin immunoprecipitation (ChIP) analysis confirmed the association of AP-1, which is composed of the oncogenic transcription factors c-Fos and c-Jun, to ERβ-bound DNA regions. Using a re-ChIP assay, we showed co-occupancy of ERβ and AP-1 on chromatin. Short interfering RNA–mediated knockdown of c-Fos or c-Jun expression decreased ERβ recruitment to chromatin, consistent with the role of AP-1 in mediating estrogen signaling in breast cancer cells. Additionally, ERα and ERβ recruitment to AP-1/ERβ target regions exhibited gene-dependent differences in response to antiestrogens. Together, our results broaden insights into ERβ DNA-binding at the genomic level by revealing crosstalk with the AP-1 transcription factor. Cancer Res; 70(12); 5174–83. ©2010 AACR.
CUB Domain–Containing Protein 1, a Prognostic Factor for Human Pancreatic Cancers, Promotes Cell Migration and Extracellular Matrix Degradation
Authors: Miyazawa Yuri , Uekita Takamasa , Hiraoka Nobuyoshi , Fujii Satoko , Kosuge Tomoo , Kanai Yae , Nojima Yoshihisa , Sakai Ryuichi 
Published: May 2010

Abstract
CUB domain–containing protein 1 (CDCP1) is a membrane protein that is highly expressed in several solid cancers. We reported previously that CDCP1 regulates anoikis resistance as well as cancer cell migration and invasion, although the underlying mechanisms have not been elucidated. In this study, we found that expression of CDCP1 in pancreatic cancer tissue was significantly correlated with overall survival and that CDCP1 expression in pancreatic cancer cell lines was relatively high among solid tumor cell lines. Reduction of CDCP1 expression in these cells suppressed extracellular matrix (ECM) degradation by inhibiting matrix metalloproteinase-9 secretion. Using the Y734F mutant of CDCP1, which lacks the tyrosine phosphorylation site, we showed that CDCP1 regulates cell migration, invasion, and ECM degradation in a tyrosine phosphorylation–dependent manner and that these CDCP1-associated characteristics were inhibited by blocking the association of CDCP1 and protein kinase Cδ (PKCδ). CDCP1 modulates the enzymatic activity of PKCδ through the tyrosine phosphorylation of PKCδ by recruiting PKCδ to Src family kinases. Cortactin, which was detected as a CDCP1-dependent binding partner of PKCδ, played a significant role in migration and invasion but not in ECM degradation of pancreatic cells. These results suggest that CDCP1 expression might play a crucial role in poor outcome of pancreatic cancer through promotion of invasion and metastasis and that molecules blocking the expression, phosphorylation, or the PKCδ-binding site of CDCP1 are potential therapeutic candidates. Cancer Res; 70(12); 5136–46. ©2010 AACR.
Notch Signaling Determines the M1 versus M2 Polarization of Macrophages in Antitumor Immune Responses
Authors: Wang Yao-Chun , He Fei , Feng Fan , Liu Xiao-Wei , Dong Guang-Ying , Qin Hong-Yan , Hu Xing-Bin , Zheng Min-Hua , Liang Liang , Feng Lei , Liang Ying-Min , Han Hua 
Published: May 2010

AbstractMacrophages are important tumor-infiltrating cells and play pivotal roles in tumor growth and metastasis. Macrophages participate in immune responses to tumors in a polarized manner: classic M1 macrophages produce interleukin (IL) 12 to promote tumoricidal responses, whereas M2 macrophages produce IL10 and help tumor progression. The mechanisms governing macrophage polarization are unclear. Here, we show that the M2-like tumor-associated macrophages (TAM) have a lower level of Notch pathway activation in mouse tumor models. Forced activation of Notch signaling increased M1 macrophages which produce IL12, no matter whether M1 or M2 inducers were applied. When Notch signaling was blocked, the M1 inducers induced M2 response in the expense of M1. Macrophages deficient in canonical Notch signaling showed TAM phenotypes. Forced activation of Notch signaling in macrophages enhanced their antitumor capacity. We further show that RBP-J–mediated Notch signaling regulates the M1 versus M2 polarization through SOCS3. Therefore, Notch signaling plays critical roles in the determination of M1 versus M2 polarization of macrophages, and compromised Notch pathway activation will lead to the M2-like TAMs. These results provide new insights into the molecular mechanisms of macrophage polarization and shed light on new therapies for cancers through the modulation of macrophage polarization through the Notch signaling. Cancer Res; 70(12); 4840–9. ©2010 AACR.
Prostate Stem Cell Antigen: A Jekyll and Hyde Molecule?
Authors: Saeki Norihisa , Gu Jian , Yoshida Teruhiko , Wu Xifeng 
Published: May 2010

Abstract
Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Although PSCA is thought to be involved in intracellular signaling, much remains unknown about its physiological function and regulatory mechanism in normal and cancer cells. It is up-regulated in several major cancers including prostate, bladder, and pancreatic cancers. The expression of PSCA is positively correlated with advanced clinical stage and metastasis in prostate cancers and is also associated with malignant progression of premalignant prostate lesions. Therefore, PSCA has been proposed as a biomarker of diagnosis and prognosis, as well as a target of therapy for these cancers. In addition, PSCA has also shown clinical potential in immunotherapy as a prostate-specific antigen, which, when presented by dendritic cells, may elicit strong tumor-specific immunity. In contrast, PSCA is down-regulated in esophageal and gastric cancer and may have a tumor-suppressing function in the gastric epithelium. Recent exciting findings that genetic variations of PSCA conferred increased risks of gastric cancer and bladder cancer have opened up a new avenue of research about the pathological function of PSCA. PSCA seems to be a Jekyll and Hyde molecule that plays differential roles, tumor promoting or suppressing, depending on the cellular context. Clin Cancer Res; 16(14); 3533–8. ©2010 AACR.
Pralatrexate Is Synergistic with the Proteasome Inhibitor Bortezomib inIn vitroandIn vivoModels of T-Cell Lymphoid Malignancies
Authors: Marchi Enrica , Paoluzzi Luca , Scotto Luigi , Seshan Venkatraman E. , Zain Jasmine M. , Zinzani Pier Luigi , O'Connor Owen A. 
Published: May 2010

AbstractPurpose: Pralatrexate (10-propargyl-10-deazaaminopterin) is an antifolate with improved cellular uptake and retention due to greater affinity for the reduced folate carrier (RFC-1) and folyl-polyglutamyl synthase. Based on the PROPEL data, pralatrexate was the first drug approved for patients with relapsed and refractory peripheral T-cell lymphoma. Bortezomib is a proteasome inhibitor that has shown some activity in patients with T-cell lymphoma.Experimental Design: Assays for cytotoxicity including mathematical analysis for synergism, flow cytometry, immunoblotting, and a xenograft severe combined immunodeficient-beige mouse model were used to explore the in vitro and in vivo activities of pralatrexate alone and in combination with bortezomib in T-cell lymphoid malignancies.Results: In vitro, pralatrexate and bortezomib exhibited concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. Pralatrexate showed synergism when combined with bortezomib in all cell lines studied. Pralatrexate also induced potent apoptosis and caspase activation when combined with bortezomib across the panel. Cytotoxicity studies on normal peripheral blood mononuclear cells showed that the combination was not more toxic than the single agents. Western blot assays for proteins involved in broad growth and survival pathways showed that p27, NOXA, HH3, and RFC-1 were all significantly modulated by the combination. In a severe combined immunodeficient-beige mouse model of transformed cutaneous T-cell lymphoma, the addition of pralatrexate to bortezomib enhanced efficacy compared with either drug alone.Conclusion: Collectively, these data suggest that pralatrexate in combination with bortezomib represents a novel and potentially important platform for the treatment of T-cell malignancies. Clin Cancer Res; 16(14); 3648–58. ©2010 AACR.
Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis
Authors: Rajasekaran Sigrid A. , Huynh Thu P. , Wolle Daniel G. , Espineda Cromwell E. , Inge Landon J. , Skay Anna , Lassman Charles , Nicholas Susanne B. , Harper Jeffrey F. , Reeves Anna E. , Ahmed Mansoor M. , Leatherman James M. , Mullin James M. , Rajasekaran Ayyappan K. 
Published: May 2010

Abstract
Epithelial-to-mesenchymal transition (EMT) is an important developmental process, participates in tissue repair, and occurs during pathologic processes of tumor invasiveness, metastasis, and tissue fibrosis. The molecular mechanisms leading to EMT are poorly understood. Although it is well documented that transforming growth factor (TGF)-β plays a central role in the induction of EMT, the targets of TGF-β signaling are poorly defined. We have shown earlier that Na,K-ATPase β1-subunit levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients' tumor samples. In this study, we provide evidence that Na,K-ATPase is a new target of TGF-β1–mediated EMT in renal epithelial cells, a model system used in studies of both cancer progression and fibrosis. We show that following treatment with TGF-β1, the surface expression of the β1-subunit of Na,K-ATPase is reduced, before well-characterized EMT markers, and is associated with the acquisition of a mesenchymal phenotype. RNAi-mediated knockdown confirmed the specific involvement of the Na,K-ATPase β1-subunit in the loss of the epithelial phenotype and exogenous overexpression of the Na,K-ATPase β1-subunit attenuated TGF-β1–mediated EMT. We further show that both Na,K-ATPase α- and β-subunit levels are highly reduced in renal fibrotic tissues. These findings reveal for the first time that Na,K-ATPase is a target of TGF-β1–mediated EMT and is associated with the progression of EMT in cancer and fibrosis. Mol Cancer Ther; 9(6); 1515–24. ©2010 AACR.
Endocytosis of PEGylated Agents Enhances Cancer Imaging and Anticancer Efficacy
Authors: Chuang Kuo-Hsiang , Wang Hsin-Ell , Chen Fang-Ming , Tzou Shey-Cherng , Cheng Chiu-Min , Chang Ya-Chen , Tseng Wei-Lung , Shiea Jentaie , Lin Shiu-Ru , Wang Jaw-Yuan , Chen Bing-Mae , Roffler Steve R. , Cheng Tian-Lu 
Published: May 2010

AbstractPEGylated nanoparticles and macromolecules are increasingly used in cancer imaging and anticancer treatment. The role of receptor-mediated endocytosis in the efficacy of these agents, however, has not been clearly defined. Here, we developed a matched pair of endocytic and nonendocytic receptors to directly and unambiguously assess this issue. The ligand-binding domains of the low-density lipoprotein receptor (LDLR) or a truncated LDLR lacking the NPXY endocytosis motif (ΔLDLR) were replaced with an anti–polyethylene glycol antibody (αPEG) to form endocytic αPEG-LDLR and nonendocytic αPEG-ΔLDLR receptors. The receptors were stably expressed at similar levels on the surface of HCC36 cells. HCC36/αPEG-LDLR cells, but not HCC36/αPEG-ΔLDLR cells, rapidly endocytosed PEG-quantum dots and PEG-liposomal doxorubicin (Lipo-Dox) in vitro and in vivo. Lipo-Dox was significantly more cytotoxic to HCC36/αPEG-LDLR cells than to HCC36/αPEG-ΔLDLR cells. HCC36/αPEG-LDLR tumors also accumulated significantly more PEGylated near-IR probes (PEG-NIR797) and PEG-liposomal-111In than HCC36/αPEG-ΔLDLR tumors in vivo. Furthermore, Lipo-Dox more significantly suppressed the growth of established HCC36/αPEG-LDLR tumors as compared with HCC36/αPEG-ΔLDLR tumors. Our data show that endocytosis of PEGylated probes and drugs enhances both cancer imaging and anticancer efficacy, indicating that endocytic receptors are superior targets for the design of cancer imaging probes and immunoliposomal drugs. Mol Cancer Ther; 9(6); 1903–12. ©2010 AACR.
Mortality in the Randomized, Controlled Lung Intergroup Trial of Isotretinoin
Authors: Lee J. Jack , Feng Lei , Reshef Daniel S. , Sabichi Anita L. , Williams Brendell , Rinsurongkawong Waree , Wistuba Ignacio I. , Lotan Reuben , Lippman Scott M. 
Published: May 2010

Abstract
In 2001, we reported that mortality may have been higher with isotretinoin (30 mg/d for 3 years) than with placebo in the subgroup of current smokers among the 1,166 patients with definitively resected early-stage non–small cell lung cancer who participated in the randomized, controlled Lung Intergroup Trial. We report the overall and cause (cancer, cardiovascular disease, or other)-specific mortality associated with long-term isotretinoin after an extended median follow-up of 6.2 years that included the capture of cause-of-death data from 428 deceased patients. Overall mortality was 36.7% in each of the two trial arms, about two thirds related to cancer and one third to other or unknown causes. Overall and cancer deaths increased in current smokers in the isotretinoin arm during the treatment and the extended follow-up period. No mortality end point increased among never smokers and former smokers taking isotretinoin, and cancer deaths decreased marginally in this combined subgroup. Isotretinoin also increased deaths from cardiovascular disease in current smokers. The present analysis supports the safety of protracted isotretinoin use in the combined group of never smokers and former smokers, which has important public health implications, for example, for treating acne in young people. The increased mortality in current smokers in this study is further evidence of the multifaceted danger of active smoking. The overall indications of this study have public health implications for treating acne in young people and other uses of retinoids in smokers. Cancer Prev Res; 3(6); 738–44. ©2010 AACR.