bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergency Department CK‐MB: A Predictor of Ischemic Complications
Authors: Hoekstra James W. , Hedges Jerris R. , Gibler W. Brian , Rubison R. Mike , Christensen Ronald A. ,   For the National Cooperative CK‐MB Project Group
Published: August 2009

ABSTRACT Objective: To demonstrate that a positive CK‐MB in the emergency department (ED) predicts an increased risk for complications of myocar‐dial ischemia in patients admitted to the hospital for evaluation of chest pain. Methods: 53 academic and community hospital EDs participated in this prospective observational cohort analysis of 5,120 patients with chest pain without ST‐segment elevation on the initial ED 12‐lead electrocardiogram. All patients were admitted for evaluation of chest pain in one of the participating hospitals as part of the National Cooperative CK‐MB Project. Patients were stratified by whether or not they had an elevated CK‐MB level in the ED. CK‐MB measurements were made on ED presentation and two hours later. Patient medical records were reviewed for inpatient diagnoses—myocardial infarction (MI) or other diagnosis —and for ischemic complications—cardiac‐related death, recurrent or delayed in‐hos‐pital MI, significant ventricular arrhythmias, new conduction defects, congestive heart failure, and cardiogenic shock. Results: 369 (7.2%) of the 5,120 patients had MI. The proportion of patients with any complication in the MI group was 24%, while the complication rate in the non‐MI group was 0.4%. In all patients, regardless of final diagnosis, the relative risk of any complication was 16.1 (95% CI 11.0–23.6) in those with a positive ED CK‐MB versus negative ED CK‐MB patients. Similarly, the relative risk of death was 25.4 (95% CI 10.8— 60.2) in positive ED CK‐MB versus negative ED CK‐MB patients. Conclusions: Multicenter data support the hypothesis that CK‐MB measurements can help risk‐stratify ED chest pain patients whose initial ECGs are without diagnostic ST‐segment elevation.
Combination Therapy Using Verteporfin and Ranibizumab; Optimizing the Timing in the CAM Model
Authors: Debefve Elodie , Pegaz Bernadette , Ballini Jean‐Pierre , Van Den Bergh Hubert 
Published: August 2009

AbstractCombining photodynamic therapy (PDT) using verteporfin (Visudyne®) with ranibizumab (Lucentis®) can optimize the overall treatment outcome by providing more efficacy in vessel closure, and thus reduce the need for retreatment in patients with wet age‐related macular degeneration. In this preclinical study in the chorioallantoic membrane (CAM) of the chicken embryo, we compare the vascular occlusion effects of verteporfin and ranibizumab as monotherapies with those observed in the combined therapy. In order to optimize the combination therapy, we varied the timing and sequence of the PDT and antivascular endothelial growth factor modalities. We observed that 1 day after PDT, the smaller blood vessels (∅ < 70 μm) of the CAM were selectively occluded, but as early as 2 days after PDT, both significant reperfusion and regrowth of new vessels were observed. Both these phenomena could be significantly delayed by application of ranibizumab. Ranibizumab itself did not induce any vascular occlusion. Under the applied conditions of combination therapy, the occlusion of the targeted blood vessels could be significantly extended to 3 days in this model compared with 1 day in the case of verteporfin monotherapy. Thus, in the present preclinical study, we demonstrate that for the applied conditions, the optimal time to administer ranibizumab is 24 h after PDT.
On the Characterization of Lifting Forces During the Rapid Compaction of Deformable Porous Media
Authors: Barabadi Banafsheh , Nathan Rungun , Jen Kei-peng , Wu Qianhong 
Published: August 2009

Abstract
In a recent paper, Wu et al. (2005, “Dynamic Compression of Highly Compressible Porous Media With Application to Snow Compaction,” J. Fluid Mech., 542, pp. 281–304) developed a novel experimental and theoretical approach to investigate the dynamic lift forces generated in the rapid compression of highly compressible porous media, (e.g., snow layer), where a porous cylinder-piston apparatus was used to measure the pore air pressure generation and a consolidation theory was developed to capture the pore-pressure relaxation process. In the current study, we extend the approach of Wu et al. to various porous materials such as synthetic fibers. The previous experimental setup was completely redesigned, where an accelerometer and a displacement sensor were employed to capture the motion of the piston. The pore-pressure relaxation during the rapid compaction of the porous material was measured. The consolidation theory developed by Wu et al. was modified by introducing the damping effect from the solid phase of the porous materials. One uses Carman–Kozeny's relationship to describe the change in the permeability as a function of compression. By comparing the theoretical results with the experimental data, we evaluated the damping effect of the soft fibers, as well as that of the pore air pressure for two different porous materials, A and B. The experimental and theoretical approach presented herein has provided an important methodology in quantifying the contributions of different forces in the lift generation inside porous media and is an extension of the previous studies done by Wu et al.
Endothelial Cell Migration and Vascular Endothelial Growth Factor Expression Are the Result of Loss of Breast Tissue Polarity
Authors: Chen Amy , Cuevas Ileana , Kenny Paraic A. , Miyake Hiroshi , Mace Kimberley , Ghajar Cyrus , Boudreau Aaron , Bissell Mina , Boudreau Nancy 
Published: August 2009

Abstract
Recruiting a new blood supply is a rate-limiting step in tumor progression. In a three-dimensional model of breast carcinogenesis, disorganized, proliferative transformed breast epithelial cells express significantly higher expression of angiogenic genes compared with their polarized, growth-arrested nonmalignant counterparts. Elevated vascular endothelial growth factor (VEGF) secretion by malignant cells enhanced recruitment of endothelial cells (EC) in heterotypic cocultures. Significantly, phenotypic reversion of malignant cells via reexpression of HoxD10, which is lost in malignant progression, significantly attenuated VEGF expression in a hypoxia-inducible factor 1α–independent fashion and reduced EC migration. This was due primarily to restoring polarity: forced proliferation of polarized, nonmalignant cells did not induce VEGF expression and EC recruitment, whereas disrupting the architecture of growth-arrested, reverted cells did. These data show that disrupting cytostructure activates the angiogenic switch even in the absence of proliferation and/or hypoxia and restoring organization of malignant clusters reduces VEGF expression and EC activation to levels found in quiescent nonmalignant epithelium. These data confirm the importance of tissue architecture and polarity in malignant progression. [Cancer Res 2009;69(16):6721–9]
Down-regulation of CXCR4 and CD62L in Chronic Lymphocytic Leukemia Cells Is Triggered by B-Cell Receptor Ligation and Associated with Progressive Disease
Authors: Vlad Amalia , Deglesne Pierre-Antoine , Letestu Rémi , Saint-Georges Stéphane , Chevallier Nathalie , Baran-Marszak Fanny , Varin-Blank Nadine , Ajchenbaum-Cymbalista Florence , Ledoux Dominique 
Published: August 2009

AbstractProgressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in the accumulation of malignant B cells. We investigated on CLL cells from 30 untreated patients the consequence of B-cell receptor (BCR) triggering on the membrane expression of CXCR4 and CD62L, two surface molecules involved in trafficking and exit of B-lymphocytes from lymph nodes. BCR stimulation promoted a strictly simultaneous down-regulation of CXCR4 and CD62L membrane expression to a variable extent. The variable BCR-dependent decrease of the two proteins was strikingly representative of the heterogeneous capacity of the CLL cells to respond to BCR engagement in a given patient. Functionally, cells down-regulating CXCR4 and CD62L in response to BCR engagement displayed a reduction in both migration toward CXCL12 and adhesion to lymphatic endothelial cells. Remarkably, the ability of CLL cells to respond to BCR ligation was correlated with unfavorable prognostic markers and short progression-free survival. In conclusion, BCR signaling promotes decrease of CXCR4 and CD62L membrane expression in progressive cases only. These results are consistent with the hypothesis that BCR-mediated signaling pathways favor accumulation of a proliferative pool within the lymph nodes of progressive CLL cases. [Cancer Res 2009;69(16):6387–95]
Antigen Presented by TumorsIn vivoDetermines the Nature of CD8+ T-Cell Cytotoxicity
Authors: Shanker Anil , Brooks Alan D. , Jacobsen Kristen M. , Wine John W. , Wiltrout Robert H. , Yagita Hideo , Sayers Thomas J. 
Published: August 2009

AbstractThe biological relevance of the perforin and Fas ligand (FasL) cytolytic pathways of CD8+ T lymphocytes (CTL) for cancer immunotherapy is controversial. We investigated the importance of these pathways in a murine renal cell carcinoma expressing influenza viral hemagglutinin as a defined surrogate antigen (Renca-HA). Following Renca-HA injection, all FasL-dysfunctional FasLgld/gld mice (n = 54) died from Renca-HA tumors by day 62. By contrast, perforin−/− (51%; n = 45) and Faslpr/lpr (55%; n = 51) mice remained tumor-free at day 360. Blocking FasL in vivo inhibited tumor rejection in these mice. Moreover, established Renca-HA tumors were cleared more efficiently by adoptively transferred HA518-526–specific T-cell receptor–transgenic CTL using FasL rather than perforin. Strikingly, a range of mouse tumor cells presenting low concentrations of immunogenic peptide were all preferentially lysed by the FasL but not the Pfp-mediated effector pathway of CTL, whereas at higher peptide concentrations, the preference in effector pathway usage by CTL was lost. Interestingly, a number of human renal cancer lines were also susceptible to FasL-mediated cytotoxicity. Therefore, the FasL cytolytic pathway may be particularly important for eradicating Fas-sensitive tumors presenting low levels of MHC class I–associated antigens following adoptive T-cell therapy. [Cancer Res 2009;69(16):6615–23]
Nicotine Stimulates PPARβ/δ Expression in Human Lung Carcinoma Cells through Activation of PI3K/mTOR and Suppression of AP-2α
Authors: Sun XiaoJuan , Ritzenthaler Jeffrey D. , Zhong XiaoRong , Zheng Ying , Roman Jesse , Han ShouWei 
Published: August 2009

Abstract
We previously showed that nicotine stimulates non–small cell lung carcinoma (NSCLC) cell proliferation through nicotinic acetylcholine receptor (nAChR)–mediated signals. Activation of peroxisome proliferator–activated receptor β/δ (PPARβ/δ) has also been shown to induce NSCLC cell growth. Here, we explore the potential link between nicotine and PPARβ/δ and report that nicotine increases the expression of PPARβ/δ protein; this effect was blocked by an α7 nAChR antagonist (α-bungarotoxin), by α7 nAChR short interfering RNA, and by inhibitors of phosphatidylinositol 3-kinase (PI3K; wortmannin and LY294002) and mammalian target of rapamycin (mTOR; rapamycin). In contrast, this effect was enhanced by PUN282987, an α7 nAChR agonist. Silencing of PPARβ/δ attenuated the stimulatory effect of nicotine on cell growth, which was overcome by transfection of an exogenous PPARβ/δ expression vector. Of note, nicotine induced complex formation between α7 nAChR and PPARβ/δ protein and increased PPARβ/δ gene promoter activity through inhibition of AP-2α as shown by reduced AP-2α binding using electrophoretic gel mobility shift and chromatin immunoprecipitation assays. In addition, silencing of Sp1 attenuated the effect of nicotine on PPARβ/δ. Collectively, our results show that nicotine increases PPARβ/δ gene expression through α7 nAChR–mediated activation of PI3K/mTOR signals that inhibit AP-2α protein expression and DNA binding activity to the PPARβ/δ gene promoter. Sp1 seems to modulate this process. This study unveils a novel mechanism by which nicotine promotes human lung carcinoma cell growth. [Cancer Res 2009;69(16):6445–53]
Discovery of BMS-641988, a Novel and Potent Inhibitor of Androgen Receptor Signaling for the Treatment of Prostate Cancer
Authors: Attar Ricardo M. , Jure-Kunkel Maria , Balog Aaron , Cvijic Mary Ellen , Dell-John Janet , Rizzo Cheryl A. , Schweizer Liang , Spires Thomas E. , Platero J. Suso , Obermeier Mary , Shan Weifang , Salvati Mark E. , Foster William R. , Dinchuk Joseph , Chen Shen-Jue , Vite Gregory , Kramer Robert , Gottardis Marco M. 
Published: August 2009

AbstractDespite an excellent initial response to first-line hormonal treatment, most patients with metastatic prostate cancer will succumb to a hormone-refractory form of the disease. Because these tumors are still dependent on a functional androgen receptor (AR), there is a need to find novel and more potent antiandrogens. While searching for small molecules that bind to the AR and inhibit its transcriptional activity, BMS-641988 was discovered. This novel antiandrogen showed an increased (&gt;1 log) potency compared with the standard antiandrogen, bicalutamide, in both binding affinity to the AR and inhibition of AR-mediated transactivation in cell-based reporter assays. In mature rats, BMS-641988 strongly inhibited androgen-dependent growth of the ventral prostate and seminal vesicles. In the CWR-22-BMSLD1 human prostate cancer xenograft model, BMS-641988 showed increased efficacy over bicalutamide (average percent tumor growth inhibition &gt;90% versus &lt;50%), even at exposure levels of bicalutamide 3-fold greater than what can be attained in humans. Furthermore, BMS-641988 was efficacious in CWR-22-BMSLD1 tumors initially refractory to treatment with bicalutamide. BMS-641988 was highly efficacious in the LuCaP 23.1 human prostate xenograft model, inducing stasis throughout the ∼30-day dosing. To explore the functional mechanisms of BMS-641988, gene expression profiling analysis was done on CWR-22-BMSLD1 xenograft models in mice. Treatment with BMS-641988 resulted in a global gene expression profile more similar to castration compared with that of bicalutamide. Overall, these data highlight that the unique preclinical profile of BMS-641988 may provide additional understanding for the hormonal treatment of prostate cancer. [Cancer Res 2009;69(16):6522–30]
Zerumbone Enhances TRAIL-Induced Apoptosis through the Induction of Death Receptors in Human Colon Cancer Cells: Evidence for an Essential Role of Reactive Oxygen Species
Authors: Yodkeeree Supachai , Sung Bokyung , Limtrakul Pornngarm , Aggarwal Bharat B. 
Published: August 2009

Abstract
Identification of the active component and mechanisms of action of traditional medicines is highly desirable. We investigated whether zerumbone, a sesquiterpene from tropical ginger, can enhance the anticancer effects of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). We found that zerumbone potentiated TRAIL-induced apoptosis in human HCT116 colon cancer cells and that this correlated with the up-regulation of TRAIL death receptor (DR) 4 and DR5. Induction of DRs occurred at the transcriptional level, and this induction was not cell-type specific, as its expression was also up-regulated in prostate, kidney, breast, and pancreatic cancer cell lines. Deletion of DR5 or DR4 by small interfering RNA significantly reduced the apoptosis induced by TRAIL and zerumbone. In addition to up-regulating DRs, zerumbone also significantly down-regulated the expression of cFLIP but not that of other antiapoptotic proteins. The induction of both DRs by zerumbone was abolished by glutathione and N-acetylcysteine (NAC), and this correlated with decreased TRAIL-induced apoptosis, suggesting a critical role of reactive oxygen species. Inhibition of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase but not of Jun NH2-terminal kinase abolished the effect of zerumbone on DR induction. Zerumbone also induced the p53 tumor suppressor gene but was found to be optional for DR induction or for enhancement of TRAIL-induced apoptosis. Both bax and p21, however, were required for zerumbone to stimulate TRAIL-induced apoptosis. Overall, our results show that zerumbone can potentiate TRAIL-induced apoptosis through the reactive oxygen species–mediated activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase leading to DR4 and DR5 induction and resulting in enhancement of the anticancer effects of TRAIL. [Cancer Res 2009;69(16):6581–9]
Intertextuality in Folklore: Pagan Themes in Jewish Folktales from the Early Modern Era
Authors: Yassif Eli 
Published: August 2009

AbstractThis article deals with the concept of intertextuality in folk narrative—a theme that has been dealt with only rarely. By analyzing the Hasidic, nineteenth-century folktale of The Sacrificers of Children, we attempt to demonstrate the importance of this theme for folkloristic scholarship and its centrality in the interpretation of folktales.The true importance of intertextuality lies in its contribution to the complexity of the text. The presence of secondary textual elements that are incorporated into the primary text but do not interfere with its ideological and aesthetic independence creates the powerful effect of multiple layers and meanings.We have here a story whose intent and purpose are distinctly and unquestionably didactic and conservative. The storyteller uses the earlier sources—biblical, midrashic, travel literature, medieval exempla—not only as narrative materials, but as references which can bring religious meaning and authority to his text. And yet it can also be read from an entirely different perspective thanks to textual elements from another world, and one which is diametrically opposed to Jewish morality. The intertextuality here is not, therefore, simply an interweaving of texts, but an existential dialogue that is conducted and deciphered by means of textual elements.
The Story of the Samaritan and the Innkeeper (Luke 10:30-35): A Study in Character Rehabilitation
Authors: Longenecker Bruce 
Published: August 2009

AbstractThe aphorism 'context is everything' has been a guiding principle in many studies of Jesus' parabolic sayings. This is true, for instance, of studies attempting to recover a parable's significance in relation to the ministry of Jesus of Nazareth, or in relation to its literary placement and function, or in relation to its polyvalent potential. It is also true of this study, which examines Jesus' narrative of the Samaritan—usually referred to as the 'parable of the good Samaritan'. It suggests that, when the Samaritan story is placed within a certain contextual configuration, its narrative features align themselves in ways that have either been conspicuously neglected or consciously avoided in the history of the story's interpretation. Rather than neglecting or avoiding the significance of these narrative features, this essay seeks to exploit their interpretative significance in a fresh manner, entertaining possibilities of meaning beyond the Lukan interpretative framework. In particular, consideration is given to the relationship between the Samaritan and the innkeeper as representing an exceptional partnership that testifies to the reign of God in making each party vulnerable to loss while promoting goodness towards others.
Exodus Inverted: A New Look at The Grapes of Wrath
Authors: Eckert Ken 
Published: August 2009

AbstractJohn Steinbeck's The Grapes of Wrath has been read typically as period social activism, as sentimental Marxist fable, and as watered-down Christian theology via its failed preacher, Jim Casy. Religious interpretations have at best seen the text as an allegorical reenactment of Exodus. Yet such criticism requires a willful misreading of the text, as the Joads end the story not in a promised land but destitute. The novel makes more sense, however, if seen as a reversal of Exodus. The Joads progress from a despoiled but occupied promised land (Oklahoma) toward bondage in Egypt (California). This extended image pattern permits Steinbeck to draw a larger thematic vision in which material poverty teaches the Joads a broadly Christian worldview. Far from ending in despair, the novel closes in the Joads emerging from a self-satisfied and legalistic moralism into a new ethos of universal love in the pattern of Christ, culminating in Rose of Sharon's spiritual maturity in her selfless act at the novel's end when the family finally moves from “I” to “we.”
Energy Production, Frictional Dissipation, and Maximum Intensity of a Numerically Simulated Tropical Cyclone*
Authors: Wang Yuqing , Xu Jing 
Published: August 2009

Abstract
A tropical cyclone (TC) viewed as a heat engine converts heat energy extracted from the ocean into the kinetic energy of the TC, which is eventually dissipated due to surface friction. Since the energy production rate is a linear function while the frictional dissipation rate is a cubic power of surface wind speed, the dissipation rate is generally smaller than the production rate initially but increases faster than the production rate as the storm intensifies. When the dissipation rate eventually reaches the production rate, the TC has no excess energy to intensify. Emanuel hypothesized that a TC achieves its maximum potential intensity (E-MPI) when the surface frictional dissipation rate balances the energy production rate near the radius of maximum wind (RMW). Although the E-MPI agrees well with the maximum intensity of numerically simulated TCs in earlier axisymmetric models, the balance hypothesis near the RMW has not been evaluated. This study shows that the frictional dissipation rate in a numerically simulated mature TC is about 25% larger than the energy production rate near the RMW, while the dissipation rate is lower than the energy production rate outside the eyewall. This finding implies that the excess frictional dissipation under the eyewall should be partially balanced by the energy production outside the eyewall and thus the local balance hypothesis underestimates the TC maximum intensity. Both Lagrangian and control volume equivalent potential temperature (θe) budget analyses demonstrate that the energy gained by boundary layer inflow air due to surface entropy fluxes outside of and prior to interaction with the eyewall contributes significantly to the energy balance in the eyewall through the lateral inward energy flux. This contribution is further verified using a sensitivity experiment in which the surface entropy fluxes are eliminated outside a radius of 30–45 km, which leads to a 13.5% reduction in the maximum sustained near-surface wind speed and a largely reduced size of the model TC.