bluuebunny/crossref_metadata_2025_split huggingface dataset:
The providence of mineral generation in the sermons of Johann Mathesius (1504–1565)
Authors: Norris John A. 
Published: March 2009

Abstract

Johann Mathesius (1504–1565) was a Protestant minister in the northern Bohemian mining town of Joachimsthal (now Jáchymov in the Czech Republic). His
Sarepta oder Bergpostill
(1562) is a collection of sermons in which he discussed various aspects of metals, minerals and mining. His description of mineral generation emphasized the ‘gur theory’, which arose within the sixteenth-century mining literature and became highly influential in the seventeenth and eighteenth centuries. The sermons contained numerous biblical references to mining and mineral generation. These did not directly correspond to the generative theories he described, and their purpose seems to have been inspirational rather than didactic. In this way, and by presenting the beauty and utility of metallic minerals as an example of God's providence, Mathesius encouraged his congregation of miners to take an interest in the more wondrous aspects of their labours. His work is significant in its consideration of mineral theories, mineral identities and terminology, and as an early example of a providential perspective that characterized many geological ideas of later centuries.
Earthquakes as God's punishment in 17th- and 18th-century Spain
Authors: Udías Agustín 
Published: March 2009

Abstract
It is generally believed that before the Enlightenment earthquakes were considered as signs of the wrath of God as punishment for men's sins, and that Earth tremors were not considered as natural occurrences until modern times. However, this is an oversimplification, as we can see in Spanish writings of the 17th and 18th centuries. In these writings we have to distinguish between popular and religious documents and academic studies. In the 17th century Spanish authors held the Aristotelian doctrine about earthquakes and regarded them as natural occurrences. Some regarded them as God's punishment for sinful people. The occurrence of a destructive earthquake in Malaga in 1680 brought this question into the open. At that time no opinions were presented against the religious interpretation. The Lisbon earthquake of 1 November 1755 and the subsequent tsunami caused considerable damage in many Spanish cities, and the earthquake was felt throughout Spain. After that earthquake an abundant literature of popular, religious, philosophical and scientific character was published. A strong controversy arose as to whether the earthquake was of natural or supernatural character, with theologians and philosophers on both sides. An important group defended the natural character of the occurrence and deplored the exaggerated position of their opponents.
The idiom of a six day creation and global depictions in Theories of the Earth
Authors: Magruder Kerry V. 
Published: March 2009

Abstract
During the 17th century, in a new contested tradition known as Theories of the Earth, conventions for the visual representation of the Earth as a whole developed alongside the expression of biblical idiom. Global depictions carried embedded biblical idiom that shaped the formulation of questions, the development of theories, and the exchange of discoveries and ideas. In several examples I contrast the varying ways in which biblical idiom was expressed within global depictions, particularly hexameral idiom (i.e. the language of the six day creation in Genesis 1). I discuss the Jesuit mathematician Gabriele Beati and meteorological and cosmic sections; the cosmogonic sections and hexameral idiom of Robert Fludd; the geogonic sections and hexameral idiom of René Descartes; the apocalyptic idiom of Thomas Burnet; and the global depictions and hexameral idiom of William Whiston in the controversy over Burnet. Biblical and particularly hexameral idiom proved durable and versatile for more than a century after Fludd, and facilitated the development of a directionalist sense of Earth history. The continuities of visual conventions, the durability of hexameral idiom, and the contrasts of disciplinary perspectives and local contexts observed in the examples considered here conform well to the characterization of Theories of the Earth as a contested print tradition.
Flood conceptions in Vallisneri's thought
Authors: Luzzini Francesco 
Published: March 2009

Abstract

The scientific studies of the Italian physician and naturalist Antonio Vallisneri (1661–1730) were concerned with the cultural and religious implications of the debate on fossils in the early decades of the eighteenth century. In
De' Corpi Marini
he summarized the main diluvial theories but declined to support them. He explained the presence of fossils in strata in mountainous regions as the result of localized multiple flood and emersion sequences, and restricted the direct action of God to the biblical Deluge. This theory clearly contradicted the biblical interpretation provided by Catholic orthodoxy, which affirmed the existence of a single global Deluge. Vallisneri therefore had to gloss over its real meaning and use a careful self-censorship system, a strategy that he frequently used in his books. The comparison with the work of several Italian and European authors had great relevance to Vallisneri's theories. He continually exchanged correspondence and natural objects with some of the most outstanding of the eighteenth century natural philosophers. This involvement with other scholars deeply influenced his thought, and helped him to reach a pre-eminent status in the Italian scientific community of the time.
The Membrane Mucin Muc4 Inhibits Apoptosis Induced by Multiple Insults via ErbB2-Dependent and ErbB2-Independent Mechanisms
Authors: Workman Heather C. , Sweeney Colleen , Carraway Kermit L. 
Published: March 2009

Abstract
The aberrant expression of membrane mucins such as Muc1 and Muc4 by tumor cells has been shown to engage signaling pathways that promote cellular properties associated with tumor progression. Our previous studies have shown that Muc4 interacts with and potentiates signaling by the ErbB2 (HER2) receptor tyrosine kinase through an epidermal growth factor–like domain in its extracellular region. Here, we show that expression of Muc4 in human A375 melanoma cells and MCF7 breast cancer cells confers resistance to apoptosis induced by a variety of stimuli, including chemotherapeutic agents, the absence of serum factors, and the loss of cellular adhesion. Mapping experiments revealed that the O-glycosylation and cytosolic domains of Muc4 are dispensable for its antiapoptotic activity, and are also dispensable for the potentiation of signaling by ErbB2. Knockdown of endogenous Muc4 in JIMT-1 breast cancer cells sensitizes cells to apoptotic stimuli, and this can be rescued by Muc4 forms lacking the O-glycosylation or cytosolic domains. Surprisingly, however, the molecular mechanisms underlying Muc4 antiapoptotic activity vary among cell lines. Although Muc4 in JIMT-1 cells engages ErbB2 to promote cell survival, its antiapoptotic mechanism in MCF7 and A375 cells seems to be independent of ErbB2. However, Muc4 expression in all cell lines culminates in the phosphorylation and inactivation of the proapoptotic protein Bad and the elevation of the prosurvival protein Bcl-xL. Our observations suggest that tumor cells can exploit the versatile antiapoptotic activities of Muc4 to acquire resistance to therapeutic agents, and augment cell survival after the loss of adhesion and microenvironment-derived survival factors. [Cancer Res 2009;69(7):2845–52]
Spleen Tyrosine Kinase Functions as a Tumor Suppressor in Melanoma Cells by Inducing Senescence-like Growth Arrest
Authors: Bailet Olivier , Fenouille Nina , Abbe Patricia , Robert Guillaume , Rocchi Stéphane , Gonthier Nadège , Denoyelle Christophe , Ticchioni Michel , Ortonne Jean-Paul , Ballotti Robert , Deckert Marcel , Tartare-Deckert Sophie 
Published: March 2009

Abstract
Loss of tumor-suppressive pathways that control cellular senescence is a crucial step in malignant transformation. Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase that has been recently implicated in tumor suppression of melanoma, a deadly skin cancer derived from pigment-producing melanocytes. However, the mechanism by which Syk suppresses melanoma growth remains unclear. Here, we report that reexpression of Syk in melanoma cells induces a p53-dependent expression of the cyclin-dependent kinase (cdk) inhibitor p21 and a senescence program. We first observed that Syk expression is lost in a subset of melanoma cell lines, primarily by DNA methylation–mediated gene silencing and restored after treatment with the demethylating agent 5-aza-2-deoxycytidine. We analyzed the significance of epigenetic inactivation of Syk and found that reintroduction of Syk in melanoma cells dramatically reduces clonogenic survival and three-dimensional tumor spheroid growth and invasion. Remarkably, melanoma cells reexpressing Syk display hallmarks of senescent cells, including reduction of proliferative activity and DNA synthesis, large and flattened morphology, senescence-associated β-galactosidase activity, and heterochromatic foci. This phenotype is accompanied by hypophosphorylated retinoblastoma protein (Rb) and accumulation of p21, which depends on functional p53. Our results highlight a new role for Syk tyrosine kinase in regulating cellular senescence and identify Syk-mediated senescence as a novel tumor suppressor pathway the inactivation of which may contribute to melanoma tumorigenicity. [Cancer Res 2009;69(7):2748–56]
The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin β1 and CXCL12
Authors: Hernandez Lorena , Smirnova Tatiana , Kedrin Dmitriy , Wyckoff Jeffrey , Zhu Liyin , Stanley E. Richard , Cox Dianne , Muller William J. , Pollard Jeffrey W. , Van Rooijen Nico , Segall Jeffrey E. 
Published: March 2009

Abstract
An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-β1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-β1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-β1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1–dependent manner. Although the invasion induced by HRG-β1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-β1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands. [Cancer Res 2009;69(7):3221–7]
Quantitative Optical Spectroscopy: A Robust Tool for Direct Measurement of Breast Cancer Vascular Oxygenation and Total Hemoglobin Content In vivo
Authors: Brown J. Quincy , Wilke Lee G. , Geradts Joseph , Kennedy Stephanie A. , Palmer Gregory M. , Ramanujam Nirmala 
Published: March 2009

Abstract
We propose the use of a robust, biopsy needle–based, fiber-optic tool for routine clinical quantification of tumor oxygenation at the time of diagnostic biopsy for breast cancer. The purpose of this study was to show diffuse reflectance spectroscopy as a quantitative tool to measure oxygenation levels in the vascular compartment of breast cancers in vivo via an optical biopsy technique. Thirty-five patients undergoing surgical treatment for breast cancer were recruited for the study at Duke University Medical Center. Diffuse reflectance spectroscopy was performed on the tumors in situ before surgical resection, followed by needle-core biopsy of the optically measured tissue. Hemoglobin saturation and total hemoglobin content were quantified from 76 optical spectra-tissue biopsy pairs, consisting of 20 malignant, 23 benign, and 33 adipose tissues. Hemoglobin saturation in malignant tissues was significantly lower than nonmalignant tissues (P &lt; 0.002) and was negatively correlated with tumor size and pathologic tumor category (P &lt; 0.05). Hemoglobin saturation was positively correlated with total hemoglobin content in malignant tissues (P &lt; 0.02). HER2/neu-amplified tumors exhibited significantly higher total hemoglobin content (P &lt; 0.05) and significantly higher hemoglobin saturation (P &lt; 0.02), which is consistent with a model of increased angiogenesis and tumor perfusion promoted by HER2/neu amplification. Diffuse reflectance spectroscopy could aid in prognosis and prediction in breast cancer via quantitative assessment of tumor physiology at the time of diagnostic biopsy. [Cancer Res 2009;69(7):2919–26]
Thyroid Transcription Factor-1 Inhibits Transforming Growth Factor-β–Mediated Epithelial-to-Mesenchymal Transition in Lung Adenocarcinoma Cells
Authors: Saito Roy-Akira , Watabe Tetsuro , Horiguchi Kana , Kohyama Tadashi , Saitoh Masao , Nagase Takahide , Miyazono Kohei 
Published: March 2009

Abstract
Thyroid transcription factor-1 (TTF-1) is expressed in lung cancer, but its functional roles remain unexplored. TTF-1 gene amplification has been discovered in a part of lung adenocarcinomas, and its action as a lineage-specific oncogene is highlighted. Epithelial-to-mesenchymal transition (EMT) is a crucial event for cancer cells to acquire invasive and metastatic phenotypes and can be elicited by transforming growth factor-β (TGF-β). Mesenchymal-to-epithelial transition (MET) is the inverse process of EMT; however, signals that induce MET are largely unknown. Here, we report a novel functional aspect of TTF-1 that inhibits TGF-β–mediated EMT and restores epithelial phenotype in lung adenocarcinoma cells. This effect was accompanied by down-regulation of TGF-β target genes, including presumed regulators of EMT, such as Snail and Slug. Moreover, silencing of TTF-1 enhanced TGF-β–mediated EMT. Thus, TTF-1 can exert a tumor-suppressive effect with abrogation of cellular response to TGF-β and attenuated invasive capacity. We further revealed that TTF-1 down-regulates TGF-β2 production in A549 cells and that TGF-β conversely decreases endogenous TTF-1 expression, suggesting that enhancement of autocrine TGF-β signaling accelerates the decrease of TTF-1 expression and vice versa. These findings delineate potential links between TTF-1 and TGF-β signaling in lung cancer progression through regulation of EMT and MET and suggest that modulation of TTF-1 expression can be a novel therapeutic strategy for treatment of lung adenocarcinoma. [Cancer Res 2009;69(7):2783–91]
Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model
Authors: Bertout Jessica A. , Patel Shetal A. , Fryer Benjamin H. , Durham Amy C. , Covello Kelly L. , Olive Kenneth P. , Goldschmidt Michael H. , Simon M. Celeste 
Published: March 2009

Abstract
Hypoxia inducible factors (HIF) are critical mediators of the cellular response to decreased oxygen tension and are overexpressed in a number of tumors. Although HIF1α and HIF2α share a high degree of sequence homology, recent work has shown that the two α subunits can have contrasting and tissue-specific effects on tumor growth. To directly compare the role of each HIFα subunit in spontaneous tumorigenesis, we bred a mouse model of expanded HIF2α expression and Hif1α+/− mice to homozygotes for the R270H mutation in p53. Here, we report that p53R270H/R270H mice, which have not been previously described, develop a unique tumor spectrum relative to p53R270H/− mice, including a high incidence of thymic lymphomas. Heterozygosity for Hif1α significantly reduced the incidence of thymic lymphomas observed in this model. Moreover, reduced Hif1α levels correlated with decreased stabilization of activated Notch1 and expression of the Notch target genes, Dtx1 and Nrarp. These observations uncover a novel role for HIF1α in Notch pathway activation during T-cell lymphomagenesis. [Cancer Res 2009;69(7):3213–20]
SLC45A3-ELK4 Is a Novel and Frequent Erythroblast Transformation–Specific Fusion Transcript in Prostate Cancer
Authors: Rickman David S. , Pflueger Dorothee , Moss Benjamin , VanDoren Vanessa E. , Chen Chen X. , de la Taille Alexandre , Kuefer Rainer , Tewari Ashutosh K. , Setlur Sunita R. , Demichelis Francesca , Rubin Mark A. 
Published: March 2009

Abstract
Chromosomal rearrangements account for all erythroblast transformation–specific (ETS) family member gene fusions that have been reported in prostate cancer and have clinical, diagnostic, and prognostic implications. Androgen-regulated genes account for the majority of the 5′ genomic regulatory promoter elements fused with ETS genes. TMPRSS2-ERG, TMPRSS2-ETV1, and SLC45A3-ERG rearrangements account for roughly 90% of ETS fusion prostate cancer. ELK4, another ETS family member, is androgen regulated, involved in promoting cell growth, and highly expressed in a subset of prostate cancer, yet the mechanism of ELK4 overexpression is unknown. In this study, we identified a novel ETS family fusion transcript, SLC45A3-ELK4, and found it to be expressed in both benign prostate tissue and prostate cancer. We found high levels of SLC45A3-ELK4 mRNA restricted to a subset of prostate cancer samples. SLC45A3-ELK4 transcript can be detected at high levels in urine samples from men at risk for prostate cancer. Characterization of the fusion mRNA revealed a major variant in which SLC45A3 exon 1 is fused to ELK4 exon 2. Based on quantitative PCR analyses of DNA, unlike other ETS fusions described in prostate cancer, the expression of SLC45A3-ELK4 mRNA is not exclusive to cases harboring a chromosomal rearrangement. Treatment of LNCaP cancer cells with a synthetic androgen (R1881) revealed that SLC45A3-ELK4, and not endogenous ELK4, mRNA expression is androgen regulated. Altogether, our findings show that SLC45A3-ELK4 mRNA expression is heterogeneous, highly induced in a subset of prostate cancers, androgen regulated, and most commonly occurs through a mechanism other than chromosomal rearrangement (e.g., trans-splicing). [Cancer Res 2009;69(7):2734–8]
EBV-Related Lymphoproliferative Disease Complicating Therapy with the Anti-CD2 Monoclonal Antibody, Siplizumab, in Patients with T-Cell Malignancies
Authors: O'Mahony Deirdre , Morris John C. , Stetler-Stevenson Maryalice , Matthews Helen , Brown Margaret R. , Fleisher Thomas , Pittaluga Stefania , Raffeld Mark , Albert Paul S. , Reitsma Dirk , Kaucic Karen , Hammershaimb Luz , Waldmann Thomas A. , Janik John E. 
Published: March 2009

AbstractPurpose: We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies.Experimental Design: We conducted a single-institution phase I dose-escalation trial of siplizumab, a humanized monoclonal antibody to CD2, in 29 patients with T-cell malignancies.Results: Although initial responses were encouraging, 4 (13.7%) patients developed EBV-LPD and the trial was stopped. Reductions in CD4+ and CD8+ cell count numbers in response to therapy were seen in all patients, but in those patients developing EBV-LPD a significantly greater reduction in natural killer (NK) cell number and CD2 expression on T cells was seen. These findings highlight the importance of NK-cell depletion and CD2 expression in addition to T-cell depletion in the etiology of EBV-LPD.Conclusions: The emergence of EBV-LPD may be associated with the ability of siplizumab to deplete both T and NK cells without affecting B cells. Agents that deplete T- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.
Combined PTEN and p27kip1 Protein Expression Patterns Are Associated with Obesity and Prognosis in Endometrial Carcinomas
Authors: Dellas Athanassios , Jundt Gernot , Sartorius Gideon , Schneider Mischa , Moch Holger 
Published: March 2009

Abstract
Purpose: Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) and p27kip1 proteins are key players of the Akt pathway, which is nutritionally regulated by insulin receptor signaling and influenced by estrogens. In this study, the prognostic relevance of the PTEN/p27kip1 protein expression in endometrial carcinoma in relationship to the body mass index (BMI) was determined.
Experimental Design: BMI and prognosis of 452 surgically treated patients with endometrial carcinoma were correlated with histologic subtype, International Federation of Gynecology and Obstetrics (FIGO) stage, and differentiation grade. The expression of PTEN and p27kip1 was examined in 257 tumors by immunohistochemistry using a tissue microarray approach.
Results: Lack of PTEN was observed in 136 of 257 (53%) tumors and absence of p27kip1 expression was observed in 106 of 225 (47%) tumors. Absence of both proteins was significantly associated with well-differentiated tumors [PTEN (P &lt; 0.02) and p27kip1 (P &lt; 0.009)]. Differentiation grade, tumor stage, and histologic type were independent of an increased BMI. Importantly, tumors of obese women expressed significantly less PTEN (P &lt; 0.008) and less p27kip1 (P &lt; 0.01) than tumors from nonobese patients. Combined absence of both PTEN and p27kip1 expression characterized a group of 75 (32%) tumors with favorable clinical outcome, particularly in the FIGO stages I and II (P = 0.003) of obese patients. Cox regression analysis revealed that PTEN/p27kip1 phenotype, FIGO stage, and histologic grade were independent predictors of prognosis in endometrioid endometrial carcinoma.
Conclusions: Inactivation of PTEN/p27kip1 proteins is a specific feature in the progression of endometrial carcinoma in obese patients. The phenotype of the combined loss of PTEN/p27kip1 protein expression in obese patients is associated with a significantly better prognosis in endometrioid endometrial carcinoma.
Stem Cells and the Natural History of Lung Cancer: Implications for Lung Cancer Screening
Authors: van Klaveren Rob J. , van't Westeinde Susan C. , de Hoop Bart-Jan , Hoogsteden Henk C. 
Published: March 2009

Abstract
Lung cancer is not simply a single disease, but a collection of several phenotypically very diverse and regionally distinct neoplasias. Its natural history is complex and not yet fully understood. Stem cells and the complex interaction with the microenvironment of the tumor and the immune system play an important role in tumor progression and metastasizing capacity. This finding explains why lung cancer does not always follow the multistep carcinogenetic and exponential growth model and why small lesions do not always equate to early-stage disease. Despite the fact that volume doubling times are increasingly used as surrogate markers for the natural history of lung cancer and as estimates for the proportion of overdiagnosed cases, it is only a momentary impression. At baseline screening especially, screen-detected lung cancer cases are preferably detected when they are in the indolent phase of their growth curve (length-biased sampling), from which it can by no means be concluded that they may not progress or metastasize at a later stage. Because the natural history of lung cancer is only partly elucidated, conclusions on the impact of overdiagnosis in lung cancer screening are premature.