bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveyor
Authors: Allen Wyatt , Erwig Martin 
Published: January 2013

Polls and surveys are increasingly employed to gather information about attitudes and experiences of all kinds of populations and user groups. The ultimate purpose of a survey is to identify trends and relationships that can inform decision makers. To this end, the data gathered by a survey must be appropriately analyzed.Most of the currently existing tools focus on the user interface aspect of the data collection task, but pay little attention to the structure and type of the collected data, which are usually represented as potentially tag-annotated, but otherwise unstructured, plain text. This makes the task of writing data analysis programs often difficult and error-prone, whereas a typed data representation could support the writing of type-directed data analysis tools that would enjoy the many benefits of static typing.In this paper we present Surveyor, a DSEL that allows the compositional construction of typed surveys, where the types describe the structure of the data to be collected. A survey can be run to gather typed data, which can then be subjected to analysis tools that are built using Surveyor's typed combinators. Altogether the Surveyor DSEL realizes a strongly typed and type-directed approach to data gathering and analysis.The implementation of our DSEL is based on GADTs to allow a flexible, yet strongly typed representation of surveys. Moreover, the implementation employs the Scrap-Your-Boilerplate library to facilitate the type-dependent traversal, extraction, and combination of data gathered from surveys.
Distinct Effects of Ligand-Induced PDGFRα and PDGFRβ Signaling in the Human Rhabdomyosarcoma Tumor Cell and Stroma Cell Compartments
Authors: Ehnman Monika , Missiaglia Edoardo , Folestad Erika , Selfe Joanna , Strell Carina , Thway Khin , Brodin Bertha , Pietras Kristian , Shipley Janet , Östman Arne , Eriksson Ulf 
Published: January 2013

Abstract
Platelet-derived growth factor receptors (PDGFR) α and β have been suggested as potential targets for treatment of rhabdomyosarcoma, the most common soft tissue sarcoma in children. This study identifies biologic activities linked to PDGF signaling in rhabdomyosarcoma models and human sample collections. Analysis of gene expression profiles of 101 primary human rhabdomyosarcomas revealed elevated PDGF-C and -D expression in all subtypes, with PDGF-D as the solely overexpressed PDGFRβ ligand. By immunohistochemistry, PDGF-CC, PDGF-DD, and PDGFRα were found in tumor cells, whereas PDGFRβ was primarily detected in vascular stroma. These results are concordant with the biologic processes and pathways identified by data mining. While PDGF-CC/PDGFRα signaling associated with genes involved in the reactivation of developmental programs, PDGF-DD/PDGFRβ signaling related to wound healing and leukocyte differentiation. Clinicopathologic correlations further identified associations between PDGFRβ in vascular stroma and the alveolar subtype and with presence of metastases. Functional validation of our findings was carried out in molecularly distinct model systems, where therapeutic targeting reduced tumor burden in a PDGFR-dependent manner with effects on cell proliferation, vessel density, and macrophage infiltration. The PDGFR-selective inhibitor CP-673,451 regulated cell proliferation through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. Additional tissue culture studies showed a PDGFR-dependent regulation of rhabdosphere formation/cancer cell stemness, differentiation, senescence, and apoptosis. In summary, the study shows a clinically relevant distinction in PDGF signaling in human rhabdomyosarcoma and also suggests continued exploration of the influence of stromal PDGFRs on sarcoma progression. Cancer Res; 73(7); 2139–49. ©2013 AACR.
G-protein Inactivator RGS6 Mediates Myocardial Cell Apoptosis and Cardiomyopathy Caused By Doxorubicin
Authors: Yang Jianqi , Maity Biswanath , Huang Jie , Gao Zhan , Stewart Adele , Weiss Robert M. , Anderson Mark E. , Fisher Rory A. 
Published: January 2013

Abstract
Clinical use of the widely used chemotherapeutic agent doxorubicin is limited by life-threatening cardiotoxicity. The mechanisms underlying doxorubicin-induced cardiomyopathy and heart failure remain unclear but are thought to involve p53-mediated myocardial cell apoptosis. The tripartite G-protein inactivating protein RGS6 has been implicated in reactive oxygen species (ROS) generation, ATM/p53 activation, and apoptosis in doxorubicin-treated cells. Thus, we hypothesized that RGS6, the expression of which is enriched in cardiac tissue, might also be responsible for the pathologic effects of doxorubicin treatment in heart. In this study, we show that RGS6 expression is induced strongly by doxorubicin in the ventricles of mice and isolated ventricular myocytes via a posttranscriptional mechanism. While doxorubicin-treated wild-type (WT) mice manifested severe left ventricular dysfunction, loss of heart and body mass, along with decreased survival 5 days after doxorubicin administration, mice lacking RGS6 were completely protected against these pathogenic responses. Activation of ATM/p53 apoptosis signaling by doxorubicin in ventricles of WT mice was also absent in their RGS6−/− counterparts. Doxorubicin-induced ROS generation was dramatically impaired in both the ventricles and ventricular myocytes isolated from RGS6−/− mice, and the apoptotic response to doxorubicin in ventricular myocytes required RGS6-dependent ROS production. These results identify RGS6 as an essential mediator of the pathogenic responses to doxorubicin in heart, and they argue that RGS6 inhibition offers a rational means to circumvent doxorubicin cardiotoxicity in human patients with cancer. Cancer Res; 73(6); 1662–7. ©2012 AACR.
Murine Microenvironment Metaprofiles Associate with Human Cancer Etiology and Intrinsic Subtypes
Authors: Nguyen David H. , Fredlund Erik , Zhao Wei , Perou Charles M. , Balmain Allan , Mao Jian-Hua , Barcellos-Hoff Mary Helen 
Published: January 2013

Abstract
Purpose: Ionizing radiation is a well-established carcinogen in rodent models and a risk factor associated with human cancer. We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53-null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts. We asked whether expression metaprofiles could discern radiation-preceded human cancer or be informative in sporadic breast cancers.
Experimental Design: Affymetrix microarray gene expression data from 56 Trp53-null mammary tumors were used to define gene profiles and a centroid that discriminates tumors arising in irradiated hosts. These were applied to publicly available human cancer datasets.
Results: Host irradiation induces a metaprofile consisting of gene modules representing stem cells, cell motility, macrophages, and autophagy. Human orthologs of the host irradiation metaprofile discriminated between radiation-preceded and sporadic human thyroid cancers. An irradiated host centroid was strongly associated with estrogen receptor–negative breast cancer. When applied to sporadic human breast cancers, the irradiated host metaprofile strongly associated with basal-like and claudin-low breast cancer intrinsic subtypes. Comparing host irradiation in the context of TGF-β levels showed that inflammation was robustly associated with claudin-low tumors.
Conclusions: Detection of radiation-preceded human cancer by the irradiated host metaprofile raises possibilities of assessing human cancer etiology. Moreover, the association of the irradiated host metaprofiles with estrogen receptor–negative status and claudin-low subtype suggests that host processes similar to those induced by radiation underlie sporadic cancers. Clin Cancer Res; 19(6); 1353–62. ©2013 AACR.
Microenvironmental Regulation of BRCA1 Gene Expression by c-Jun and Fra2 in Premalignant Human Ovarian Surface Epithelial Cells
Authors: Zhou Lixin , Graves Marcia , MacDonald Gwen , Cipollone Jane , Mueller Christopher R. , Roskelley Calvin D. 
Published: January 2013

Abstract
Reduced BRCA1 gene expression is common in the sporadic form of ovarian carcinoma. The spread of this highly lethal cancer often begins when tumor cell clusters are shed into the fluid of the abdominopelvic cavity such that they can float freely before seeding distant sites on the peritoneal walls and organs. Thus, the microenvironment that tumor cells find themselves in changes dramatically during these early shedding and floating stages of transperitoneal metastasis. To mimic this microenvironmental change in vitro, we released premalignant human ovarian surface epithelial cells from the substratum and forced them to cluster in suspension. Under these conditions, steady state levels of BRCA1 mRNA and protein fell significantly and the transcriptional activation state of the BRCA1 promoter was suppressed. Analysis of the promoter indicated that the previously identified “CRE” element located within the “positive regulatory region” (PRR) contributed to this suppression. More specifically, we show that the suppression was mediated, at least in part, by a suspension culture–driven decrease in the levels of two members of the AP1 transcription factor complex, c-Jun and Fra2, that bind to the CRE element. Therefore, a microenvironmental change that is manifested during the initial stages of ovarian carcinoma dissemination may, potentially, help suppress BRCA1 expression in sporadic tumors and thus promote their progression. Mol Cancer Res; 11(3); 272–81. ©2013 AACR.
The Heterochronic microRNA let-7 Inhibits Cell Motility by Regulating the Genes in the Actin Cytoskeleton Pathway in Breast Cancer
Authors: Hu Xiaowen , Guo Jinyi , Zheng Lan , Li Chunsheng , Zheng Tim M. , Tanyi Janos L. , Liang Shun , Benedetto Chiara , Mitidieri Marco , Katsaros Dionyssios , Zhao Xia , Zhang Youcheng , Huang Qihong , Zhang Lin 
Published: January 2013

Abstract
The heterochronic gene let-7 serves as a tumor suppressor microRNA by targeting various oncogenic pathways in cancer cells. Considerable evidence indicates that reduced expression of let-7 might be associated with poor clinical outcome in patients with cancer. Here, we report that the expression levels of three let-7 family members, let-7a, let-7b, and let-7g, were significantly decreased in the patients with breast cancer with lymph node metastasis compared with those without lymph node metastasis. Enforced expression of let-7b significantly inhibits breast cancer cell motility and affects actin dynamics. Using bioinformatic and experimental approaches, four genes in the actin cytoskeleton pathway, including PAK1, DIAPH2, RDX, and ITGB8, were identified as let-7 direct targets. Blocking the expression of PAK1, DIAPH2, and RDX significantly inhibits breast cancer cell migration induced by let-7b repression. Our results indicate that reconstitution of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of metastatic disease. Mol Cancer Res; 11(3); 240–50. ©2013 AACR.
Targeting Constitutively Activated β1 Integrins Inhibits Prostate Cancer Metastasis
Authors: Lee Yu-Chen , Jin Jung-Kang , Cheng Chien-Jui , Huang Chih-Fen , Song Jian H. , Huang Miao , Brown Wells S. , Zhang Sui , Yu-Lee Li-Yuan , Yeh Edward T. , McIntyre Bradley W. , Logothetis Christopher J. , Gallick Gary E. , Lin Sue-Hwa 
Published: January 2013

Abstract
Disseminated prostate cancer cells must survive in circulation for metastasis to occur. Mechanisms by which these cells survive are not well understood. By immunohistochemistry of human tissues, we found that levels of β1 integrins and integrin-induced autophosphorylation of FAK (pFAK-Y397) are increased in prostate cancer cells in primary prostate cancer and lymph node metastases, suggesting that β1 integrin activation occurs in metastatic progression of prostate cancer. A conformation-sensitive antibody, 9EG7, was used to examine β1 integrin activation. We found that β1 integrins are constitutively activated in highly metastatic PC3 and PC3-mm2 cells, with less activation in low metastatic LNCaP and C4-2B4 cells. Increased β1 integrin activation as well as the anoikis resistance in prostate cancer cells correlated with metastatic potential in vivo. Knockdown of β1 integrin abrogated anoikis resistance in PC3-mm2 cells. In agreement with β1 integrin activation, PC3-mm2 cells strongly adhered to type I collagen and fibronectin, a process inhibited by the β1 integrin-neutralizing antibody mAb 33B6. mAb 33B6 also inhibited the phosphorylation of β1 integrin downstream effectors, focal adhesion kinase (FAK) and AKT, leading to a 3-fold increase in PC3-mm2 apoptosis. Systemic delivery of mAb 33B6 suppressed spontaneous metastasis of PC3-mm2 from the prostate to distant lymph nodes following intraprostatic injection and suppressed metastasis of PC3-mm2 to multiple organs following intracardiac injection. Thus, constitutively activated β1 integrins play a role in survival of PC3-mm2 cells in circulation and represent a potential target for metastasis prevention.
Visual Overview: http://mcr.aacrjournals.org/content/11/4/405/F1.large.jpg.
Mol Cancer Res; 11(4); 405–17. ©2013 AACR.
Chemical Characteristics of Aerosol Composition over the Yellow Sea and the East China Sea in Autumn*
Authors: Zhang Hong-Hai , Yang Gui-Peng , Liu Chun-Ying , Su Lu-Ping 
Published: January 2013

Abstract
The total suspended particulate (TSP) samples over the Yellow Sea and the East China Sea were collected to determine the major compositions of water-soluble ionic species during two cruises in autumn 2007. The aerosol compositions exhibited an obvious regional variation between the two cruises, with higher concentrations (except Na+ and Mg2+) over the northern Yellow Sea during the first cruise. The concentrations of the secondary ions [non–sea salt sulfate (nss-), , and ] were 11 ± 4.9, 3.1 ± 2.1, and 3.7 ± 2.6 μg m−3, respectively, which together contributed over 72% of the total determined ion concentrations. Significant correlations between these secondary ions were found within each sampling period, while nss-K+ and nss-Ca2+ showed strong correlation with each other. The calculated results of equivalent concentrations of anions (nss- and ) and cations ( and Ca2+) showed that the acidic species were mostly neutralized with the alkaline species over the study areas. The mass ratio of nss-/ was 1.4 during the investigation period. In addition, the concentrations of MSA were 0.011 ± 0.044 and 0.0081 ± 0.0047 μg m−3 during the two cruises, respectively. Based on the measured MSA, nss-, and their ratios, the relative biogenic sulfur contribution to the total nss- was estimated to be only 2.0% during the two cruises, further suggesting the major contribution of anthropogenic source to sulfur budget over the marginal seas of China.
Transient Climate Response in Coupled Atmospheric–Ocean General Circulation Models
Authors: Liang Mao-Chang , Lin Li-Ching , Tung Ka-Kit , Yung Yuk L. , Sun Shan 
Published: January 2013

Abstract
The equilibrium climate sensitivity (ECS) has a large uncertainty range among models participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) and has recently been presented as “inherently unpredictable.” One way to circumvent this problem is to consider the transient climate response (TCR). However, the TCR among AR4 models also differs by more than a factor of 2. The authors argue that the situation may not necessarily be so pessimistic, because much of the intermodel difference may be due to the fact that the models were run with their oceans at various stages of flux adjustment with their atmosphere. This is shown by comparing multimillennium-long runs of the Goddard Institute for Space Studies model, version E, coupled with the Hybrid Coordinate Ocean Model (GISS-EH) and the Community Climate System Model, version 4 (CCSM4) with what were reported to AR4. The long model runs here reveal the range of variability (~30%) in their TCR within the same model with the same ECS. The commonly adopted remedy of subtracting the “climate drift” is ineffective and adds to the variability. The culprit is the natural variability of the control runs, which exists even at quasi equilibration. Fortunately, for simulations with multidecadal time horizon, robust solutions can be obtained by branching off thousand-year-long control runs that reach “quasi equilibration” using a new protocol, which takes advantage of the fact that forced solutions to radiative forcing forget their initial condition after 30–40 yr and instead depend mostly on the trajectory of the radiative forcing.
The Atlantic Meridional Heat Transport at 26.5°N and Its Relationship with the MOC in the RAPID Array and the GFDL and NCAR Coupled Models
Authors: Msadek Rym , Johns William E. , Yeager Stephen G. , Danabasoglu Gokhan , Delworth Thomas L. , Rosati Anthony 
Published: January 2013

Abstract
The link at 26.5°N between the Atlantic meridional heat transport (MHT) and the Atlantic meridional overturning circulation (MOC) is investigated in two climate models, the GFDL Climate Model version 2.1 (CM2.1) and the NCAR Community Climate System Model version 4 (CCSM4), and compared with the recent observational estimates from the Rapid Climate Change–Meridional Overturning Circulation and Heatflux Array (RAPID–MOCHA) array. Despite a stronger-than-observed MOC magnitude, both models underestimate the mean MHT at 26.5°N because of an overly diffuse thermocline. Biases result from errors in both overturning and gyre components of the MHT. The observed linear relationship between MHT and MOC at 26.5°N is realistically simulated by the two models and is mainly due to the overturning component of the MHT. Fluctuations in overturning MHT are dominated by Ekman transport variability in CM2.1 and CCSM4, whereas baroclinic geostrophic transport variability plays a larger role in RAPID. CCSM4, which has a parameterization of Nordic Sea overflows and thus a more realistic North Atlantic Deep Water (NADW) penetration, shows smaller biases in the overturning heat transport than CM2.1 owing to deeper NADW at colder temperatures. The horizontal gyre heat transport and its sensitivity to the MOC are poorly represented in both models. The wind-driven gyre heat transport is northward in observations at 26.5°N, whereas it is weakly southward in both models, reducing the total MHT. This study emphasizes model biases that are responsible for the too-weak MHT, particularly at the western boundary. The use of direct MHT observations through RAPID allows for identification of the source of the too-weak MHT in the two models, a bias shared by a number of Coupled Model Intercomparison Project phase 5 (CMIP5) coupled models.
Control of Mode and Intermediate Water Mass Properties in Drake Passage by the Amundsen Sea Low
Authors: Close Sally E. , Naveira Garabato Alberto C. , McDonagh Elaine L. , King Brian A. , Biuw Martin , Boehme Lars 
Published: January 2013

Abstract
The evolution of the physical properties of Subantarctic Mode Water (SAMW) and Antarctic Intermediate Water (AAIW) in the Drake Passage region is examined on time scales down to intraseasonal, within the 1969–2009 period. Both SAMW and AAIW experience substantial interannual to interdecadal variability, significantly linked to the action of the Amundsen Sea low (ASL) in their formation areas. Observations suggest that the interdecadal freshening tendency evident in SAMW over the past three decades has recently abated, while AAIW has warmed significantly since the early 2000s. The two water masses have also experienced a substantial lightening since the start of the record. Examination of the mechanisms underpinning water mass property variability shows that SAMW characteristics are controlled predominantly by a combination of air–sea turbulent heat fluxes, cross-frontal Ekman transport of Antarctic surface waters, and the evaporation–precipitation balance in the Subantarctic zone of the southeast Pacific and Drake Passage, while AAIW properties reflect air–sea turbulent heat fluxes and sea ice formation in the Bellingshausen Sea. The recent interdecadal evolution of the ASL is consistent with both the dominance of the processes described here and the response of SAMW and AAIW on that time scale.
Radiative and Dynamical Forcing of the Surface and Atmospheric Temperature Anomalies Associated with the Northern Annular Mode
Authors: Deng Yi , Park Tae-Won , Cai Ming 
Published: January 2013

Abstract
On the basis of the total energy balance within an atmosphere–surface column, an attribution analysis is conducted for the Northern Hemisphere (NH) atmospheric and surface temperature response to the northern annular mode (NAM) in boreal winter. The local temperature anomaly in the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim) is decomposed into partial temperature anomalies because of changes in atmospheric dynamics, water vapor, clouds, ozone, surface albedo, and surface dynamics with the coupled atmosphere–surface climate feedback–response analysis method (CFRAM). Large-scale ascent/descent as part of the NAM-related mean meridional circulation anomaly adiabatically drives the main portion of the observed zonally averaged atmospheric temperature response, particularly the tropospheric cooling/warming over northern extratropics. Contributions from diabatic processes are generally small but could be locally important, especially at lower latitudes where radiatively active substances such as clouds and water vapor are more abundant. For example, in the tropical upper troposphere and stratosphere, both cloud and ozone forcings are critical in leading to the observed NAM-related temperature anomalies. Radiative forcing due to changes in water vapor acts as the main driver of the surface warming of southern North America during a positive phase of NAM, with atmospheric dynamics providing additional warming. In the negative phase of NAM, surface albedo change drives the surface cooling of southern North America, with atmospheric dynamics providing additional cooling. Over the subpolar North Atlantic and northern Eurasia, atmospheric dynamical processes again become the largest contributor to the NAM-related surface temperature anomalies, although changes in water vapor and clouds also contribute positively to the observed surface temperature anomalies while change in surface dynamics contributes negatively to the observed temperature anomalies.