bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of FOXO3a Is Sufficient to Reverse Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor Chemoresistance in Human Cancer
Authors: Yang Jer-Yen , Chang Chun-Ju , Xia Weiya , Wang Yan , Wong Kwok-Kin , Engelman Jeffrey A. , Du Yi , Andreeff Michael , Hortobagyi Gabriel N. , Hung Mien-Chie 
Published: May 2010

Abstract
Drug resistance is a central challenge of cancer therapy that ultimately leads to treatment failure. In this study, we characterized a mechanism of drug resistance that arises to AZD6244, an established mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitor currently being evaluated in cancer clinical trials. AZD6244 enhanced the expression of transcription factor FOXO3a, which suppressed cancer cell proliferation. In AZD6244-resistant cancer cells, we observed the impaired nuclear localization of FOXO3a, reduced FOXO3a-mediated transcriptional activity, and decreased the expression of FOXO3a target gene Bim after cell treatment with AZD6244. Resistant cells could be sensitized by phosphoinositide 3-kinase (PI3K)/AKT inhibitors, which are known to enhance FOXO3a nuclear translocation. Our findings define FOXO3a as candidate marker to predict the clinical efficacy of AZD6244. Furthermore, they suggest a mechanism of resistance to MEK inhibitors that may arise in the clinic yet can be overcome by cotreatment with PI3K/AKT inhibitors. Cancer Res; 70(11); 4709–18. ©2010 AACR.
Downregulation of MicroRNA-200 in EBV-Associated Gastric Carcinoma
Authors: Shinozaki Aya , Sakatani Takashi , Ushiku Tetsuo , Hino Rumi , Isogai Maya , Ishikawa Shunpei , Uozaki Hiroshi , Takada Kenzo , Fukayama Masashi 
Published: May 2010

AbstractEBV-associated gastric carcinoma is a distinct gastric carcinoma subtype with characteristic morphologic features similar to those of cells that undergo epithelial-to-mesenchymal transition. The effect of microRNA abnormalities in carcinogenesis was investigated by measuring the expression of the epithelial-to-mesenchymal transition–related microRNAs, miR-200a and miR-200b, in 36 surgically resected gastric carcinomas using quantitative reverse transcription-PCR analysis. MiR-200 family expression was decreased in EBV-associated gastric carcinoma, as compared with that in EBV-negative carcinoma. Downregulation of the miR-200 family was found in gastric carcinoma cell lines infected with recombinant EBV (MKN74-EBV, MKN7-EBV, and NUGC3-EBV), accompanied by the loss of cell adhesion, reduction of E-cadherin expression, and upregulation of ZEB1 and ZEB2. E-cadherin expression was partially restored by transfection of EBV-infected cells with miR-200 family precursors. Reverse transcription-PCR analysis of primary precursors of miR-200 (pri-miR-200) revealed that the transcription of pri-miR-200 was decreased in EBV-infected cells. Transfection of MKN74 cells with BARF0, EBNA1, and LMP2A resulted in a decrease of pri-miR-200, whereas transfection with EBV-encoded small RNA (EBER) did not. These four latent genes contributed to the downregulation of the mature miR-200 family and the subsequent upregulation of ZEB1/ZEB2, resulting in the reduction of E-cadherin expression. These findings indicate that all the latency type I genes have a synergetic effect on the downregulation of the miR-200 family that leads to reduced E-cadherin expression, which is a crucial step in the carcinogenesis of EBV-associated gastric carcinoma. Cancer Res; 70(11); 4719–27. ©2010 AACR.
Notch1 Functions as a Tumor Suppressor in a Model of K-ras–Induced Pancreatic Ductal Adenocarcinoma
Authors: Hanlon Linda , Avila Jacqueline L. , Demarest Renée M. , Troutman Scott , Allen Megan , Ratti Francesca , Rustgi Anil K. , Stanger Ben Z. , Radtke Fred , Adsay Volkan , Long Fenella , Capobianco Anthony J. , Kissil Joseph L. 
Published: May 2010

Abstract
K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras–induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased tumor incidence and progression, implying that Notch1 can function as a tumor suppressor gene in PDAC. Cancer Res; 70(11); 4280–6. ©2010 AACR.
Benzyl Isothiocyanate–Mediated Inhibition of Histone Deacetylase Leads to NF-κB Turnoff in Human Pancreatic Carcinoma Cells
Authors: Batra Sanjay , Sahu Ravi P. , Kandala Prabodh K. , Srivastava Sanjay K. 
Published: May 2010

AbstractNF-κB/p65 is constitutively activated in pancreatic cancers, where it plays a critical role in the transcriptional activation of multiple cell survival genes. We have previously shown the apoptosis-inducing effects of benzyl isothiocyanate (BITC) in pancreatic cancer cells. We hypothesized that inhibition of NF-κB/p65 could be the mechanism of BITC-induced apoptosis. Therefore, the effect of BITC on NF-κB/p65 was evaluated in BxPC-3, Capan-2, and normal HPDE-6 cells by Western blotting, transcriptional and DNA-binding activity, and immunohistochemistry in the xenografted tumors. Our results reveal a remarkable decrease in the phosphorylation of NF-κB/p65 at Ser536 in both BxPC-3 and Capan-2 cells by BITC treatment. The expression of NF-κB/p65 was downregulated significantly in BxPC-3 cells, whereas it remained unchanged in Capan-2 cells. BITC treatment caused a significant decrease in NF-κB transcriptional and DNA-binding activity in both BxPC-3 and Capan-2 cells. A drastic decrease was observed in the expression and reporter activity of cyclin D1 in both the cell lines. Moreover, BITC also caused a significant decrease in the expression and activity of histone deacetylase (HDAC) 1 and HDAC3 in BxPC-3 and HDAC3 in Capan-2 cells. Overexpression of HDAC1 or HDAC3 abrogated the effects of BITC. BITC treatment did not cause any change in HDAC expression in normal HPDE-6 cells. Immunohistochemical analysis of tumors from BITC-treated mice showed significantly reduced staining for NF-κB, cyclin D1, HDAC1, and HDAC3 compared with control. Our results suggest inhibition of HDAC1/HDAC3 by BITC as a plausible mechanism of NF-κB inactivation, resulting in the in vitro and in vivo growth suppression of pancreatic cancer cells. Mol Cancer Ther; 9(6); 1596–608. ©2010 AACR.
ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity
Authors: Munshi Neru , Jeay Sébastien , Li Youzhi , Chen Chang-Rung , France Dennis S. , Ashwell Mark A. , Hill Jason , Moussa Magdi M. , Leggett David S. , Li Chiang J. 
Published: May 2010

Abstract
The met proto-oncogene is functionally linked with tumorigenesis and metastatic progression. Validation of the receptor tyrosine kinase c-Met as a selective anticancer target has awaited the emergence of selective c-Met inhibitors. Herein, we report ARQ 197 as the first non-ATP–competitive small molecule that selectively targets the c-Met receptor tyrosine kinase. Exposure to ARQ 197 resulted in the inhibition of proliferation of c-Met–expressing cancer cell lines as well as the induction of caspase-dependent apoptosis in cell lines with constitutive c-Met activity. These cellular responses to ARQ 197 were phenocopied by RNAi-mediated c-Met depletion and further demonstrated by the growth inhibition of human tumors following oral administration of ARQ 197 in multiple mouse xenograft efficacy studies. Cumulatively, these data suggest that ARQ 197, currently in phase II clinical trials, is a promising agent for targeting cancers in which c-Met-driven signaling is important for their survival and proliferation. Mol Cancer Ther; 9(6); 1544–53. ©2010 AACR.
Long-Term Outcome of Adjunctive Celecoxib Treatment After Paclitaxel-Eluting Stent Implantation for the Complex Coronary Lesions
Authors: Chung Jin-Wook , Yang Han-Mo , Park Kyung-Woo , Lee Hae-Young , Park Jin-Shik , Kang Hyun-Jae , Cho Young-Seok , Youn Tae-Jin , Koo Bon-Kwon , Chae In-Ho , Choi Dong-Ju , Oh Byung-Hee , Park Young-Bae , Kim Hyo-Soo 
Published: May 2010

Background—
In the COREA-TAXUS trial (“Effect of Celecoxib On REstenosis after coronary Angioplasty with a TAXUS stent”), celecoxib reduced late luminal loss and adverse cardiac events at follow-up around 6 months. The objective of this study was to assess the long-term outcome of short-term adjunctive celecoxib treatment after paclitaxel-eluting stent implantation.

Methods and Results—

This is a 2-year clinical follow-up of the COREA-TAXUS trial, an open-label randomized controlled study. A total 274 patients were randomized to receive or not receive celecoxib (400 mg before the intervention and 200 mg twice daily for 6 months after the procedure), and 271 underwent successful paclitaxel-eluting stent implantation. All patients were given aspirin (100 mg daily indefinitely) and clopidogrel (75 mg daily for at least 6 months). Among the 271 patients, 267 (98.5%) completed the 2-year clinical follow-up. From the previous follow-up to 2 years, there was no difference in the rate of adverse cardiac events between the celecoxib and control groups (1.6% versus 4.3%,
P
=0.27). Thus, at 2 years, the rate of adverse cardiac events was consistently lower in the celecoxib group (6.9% versus 19.7%,
P
=0.002). A significant reduction in need for target lesion revascularization was observed (6.2% versus 18.2%,
P
=0.003). The efficacy benefit in the celecoxib group was not undermined by an increased risk for cardiac death or myocardial infarction at 2 years (1.5% versus 1.4%).

Conclusions—
Six-month adjunctive celecoxib treatment after paclitaxel-eluting stent implantation was associated with durable long-term efficacy up to 2 years. However, the inconclusive evidence for the long-term safety of this treatment warrants caution.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT 00292721.
Concurrent Microvascular and Infarct Remodeling After Successful Reperfusion of ST-Elevation Acute Myocardial Infarction
Authors: Sezer Murat , Aslanger Emre K. , Cimen Arif O. , Yormaz Ebru , Turkmen Cuneyt , Umman Berrin , Nisanci Yılmaz , Bugra Zehra , Adalet Kamil , Umman Sabahattin 
Published: May 2010

Background—
Connection between the course of microvascular and infarct remodeling processes over time after reperfused ST-elevation acute myocardial infarction has not been fully elucidated. The aim of this study is to investigate the association of temporal changes in hemodynamics of microcirculation in the infarcted territory and infarct size (IS) after primary percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

Methods and Results—

Thirty-five patients admitted with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention were enrolled in the study. Coronary flow reserve (CFR), index of microvascular resistance (IMR), and IS were assessed 2 days after primary percutaneous coronary intervention and at the 5-month follow-up. The predictors of the 5-month IS were the baseline values of IS (β=0.6,
P
<0.001), IMR (β=0.280,
P
=0.013), and CFR (β=−0.276,
P
=0.017). There were significant correlations between relative change in IS and relative change in measures of microvascular function (IS and CFR [
r
=−0.51,
P
=0.002]); IS and IMR ([
r
=0.55,
P
=0.001]). In multivariate model, relative changes in IMR (β=0.552,
P
=0.001) and CFR (β=−0.511,
P
=0.002) were the only predictors of relative change in IS. In patients with an improvement in IMR >33%, the mean IS decreased from 32.3±16.9% to 19.3±14% (
P
=0.001) in the follow-up. Similarly, in patients with an improvement in CFR >41%, the mean IS significantly decreased from 29.9±20% to 15.8±12.4% (
P
=0.003). But in patients with an improvement in IMR and CFR, which were below than the mean values, IS did not significantly decrease during the follow-up.

Conclusions—
Improvement in microvascular function in the infarcted territory is associated with reduction in IS after reperfused ST-elevation acute myocardial infarction. This link suggests that further investigations are warranted to determine whether therapeutic protection of microvascular integrity results in augmentation of infarct healing.
Led Astray by Punctuation The Meaning of πιορκ in Matt 5:33
Authors: Lee John A.L. 
Published: May 2010

AbstractThe meaning of πιορκ in Matt 5:33 remains uncertain in the NT lexicon of Bauer in English and in major commentaries. This paper traces the problem in Bauer to misreading of punctuation. A re-examination of the evidence establishes that the appropriate meaning is break one’s sworn promise, and this is seen to be the meaning Bauer intended.
James 1:2-15 and Hellenistic Psychagogy
Authors: Kloppenborg John S. 
Published: May 2010

AbstractIn elaborating the Jesus tradition (Q 11:9-10; 6:22-23) James expands, compresses and elaborates Q sayings in a way which reveals an array of interests in psychagogy and the care of the soul which we know also to have characterized various strains of Hellenistic philosophy of the early Roman period. The author of James displays a remarkable interest, not in such concrete ends as subsistence, debt relief, and the rewards for withstanding persecution, but rather in the psychic processes that occur between stimulus and decision and in the role that proper cognition plays in constructing the subject as perfect.
Circumpolar Arctic Tundra Vegetation Change Is Linked to Sea Ice Decline
Authors: Bhatt Uma S. , Walker Donald A. , Raynolds Martha K. , Comiso Josefino C. , Epstein Howard E. , Jia Gensuo , Gens Rudiger , Pinzon Jorge E. , Tucker Compton J. , Tweedie Craig E. , Webber Patrick J. 
Published: May 2010

AbstractLinkages between diminishing Arctic sea ice and changes in Arctic terrestrial ecosystems have not been previously demonstrated. Here, the authors use a newly available Arctic Normalized Difference Vegetation Index (NDVI) dataset (a measure of vegetation photosynthetic capacity) to document coherent temporal relationships between near-coastal sea ice, summer tundra land surface temperatures, and vegetation productivity. The authors find that, during the period of satellite observations (1982–2008), sea ice within 50 km of the coast during the period of early summer ice breakup declined an average of 25% for the Arctic as a whole, with much larger changes in the East Siberian Sea to Chukchi Sea sectors (&gt;44% decline). The changes in sea ice conditions are most directly relevant and have the strongest effect on the villages and ecosystems immediately adjacent to the coast, but the terrestrial effects of sea ice changes also extend far inland. Low-elevation (&lt;300 m) tundra summer land temperatures, as indicated by the summer warmth index (SWI; sum of the monthly-mean temperatures above freezing, expressed as °C month−1), have increased an average of 5°C month−1 (24% increase) for the Arctic as a whole; the largest changes (+10° to 12°C month−1) have been over land along the Chukchi and Bering Seas. The land warming has been more pronounced in North America (+30%) than in Eurasia (16%). When expressed as percentage change, land areas in the High Arctic in the vicinity of the Greenland Sea, Baffin Bay, and Davis Strait have experienced the largest changes (&gt;70%). The NDVI has increased across most of the Arctic, with some exceptions over land regions along the Bering and west Chukchi Seas. The greatest change in absolute maximum NDVI occurred over tundra in northern Alaska on the Beaufort Sea coast [+0.08 Advanced Very High Resolution Radiometer (AVHRR) NDVI units]. When expressed as percentage change, large NDVI changes (10%–15%) occurred over land in the North America High Arctic and along the Beaufort Sea. Ground observations along an 1800-km climate transect in North America support the strong correlations between satellite NDVI observations and summer land temperatures. Other new observations from near the Lewis Glacier, Baffin Island, Canada, document rapid vegetation changes along the margins of large retreating glaciers and may be partly responsible for the large NDVI changes observed in northern Canada and Greenland. The ongoing changes to plant productivity will affect many aspects of Arctic systems, including changes to active-layer depths, permafrost, biodiversity, wildlife, and human use of these regions. Ecosystems that are presently adjacent to year-round (perennial) sea ice are likely to experience the greatest changes.
Physical Climate Response to a Reduction of Anthropogenic Climate Forcing
Authors: Samanta Arindam , Anderson Bruce T. , Ganguly Sangram , Knyazikhin Yuri , Nemani Ramakrishna R. , Myneni Ranga B. 
Published: May 2010

Abstract
Recent research indicates that the warming of the climate system resulting from increased greenhouse gas (GHG) emissions over the next century will persist for many centuries after the cessation of these emissions, principally because of the persistence of elevated atmospheric carbon dioxide (CO2) concentrations and their attendant radiative forcing. However, it is unknown whether the responses of other components of the climate system—including those related to Greenland and Antarctic ice cover, the Atlantic thermohaline circulation, the West African monsoon, and ecosystem and human welfare—would be reversed even if atmospheric CO2 concentrations were to recover to 1990 levels. Here, using a simple set of experiments employing a current-generation numerical climate model, the authors examine the response of the physical climate system to decreasing CO2 concentrations following an initial increase. Results indicate that many characteristics of the climate system, including global temperatures, precipitation, soil moisture, and sea ice, recover as CO2 concentrations decrease. However, other components of the Earth system may still exhibit nonlinear hysteresis. In these experiments, for instance, increases in stratospheric water vapor, which initially result from increased CO2 concentrations, remain present even as CO2 concentrations recover. These results suggest that identification of additional threshold behaviors in response to human-induced global climate change should focus on subcomponents of the full Earth system, including cryosphere, biosphere, and chemistry.
A Method to Infer the Three Cartesian Wavelengths of a Mountain Wave from Three Soundings
Authors: Alexander P. , de la Torre A. 
Published: May 2010

Abstract
The number of atmospheric sounding techniques and the amount of missions within each of them continue to grow at the present time. The probability of having two or more profiles in a given region and time interval therefore is increasing. In the case of three close observations it would be a priori possible to infer the three Cartesian wavelengths of a mountain wave. However, the relative orientation of the three sounding paths cannot be arbitrary and must fulfill some conditions to avoid errors growing out of given bounds.
Climatology of Anomalous Propagation Radar Echoes in a Coastal Area
Authors: Mesnard Frédéric , Sauvageot Henri 
Published: May 2010

Abstract
Anomalous propagation (AP) of ground-based radar beam results in the detection of ground echoes beyond the horizon. One year of data gathered with an S-band meteorological radar located on the coast in southwest France is used to analyze the spatial distribution of AP ground echoes (APE). The APE distributions of duration and reflectivity in the radar-observed area are found to be strongly related to the main feature of the regional orography and topography up to the farthest distance (250 km) observed by the radar, notably the nature of the surface, the topographic orientation with respect to the radar beam direction, and the altitude. The distribution of APE in the studied area is found to be strongly anisotropic around the radar, with wide differences between land and sea. Rain accumulation equivalent to the APE is, in certain places, of the same order or higher than the real rain depth. The distribution of the ground surfaces, as calculated from a ground numerical model, compares qualitatively well with the APE radar reflectivity distribution.
Objectively Determining the Rotational Center of Tropical Cyclones in Passive Microwave Satellite Imagery
Authors: Wimmers Anthony J. , Velden Christopher S. 
Published: May 2010

Abstract
Precise center-fixing of tropical cyclones (TCs) is critical for operational forecasting, intensity estimation, and visualization. Current procedures are usually performed with manual input from a human analyst, using multispectral satellite imagery as the primary tools. While adequate in many cases, subjective interpretation can often lead to variance in the estimated center positions. In this paper an objective, robust algorithm is presented for resolving the rotational center of TCs: the Automated Rotational Center Hurricane Eye Retrieval (ARCHER). The algorithm finds the center of rotation using spirally oriented brightness temperature gradients in the TC banding patterns in combination with gradients along the ring-shaped edge of a possible eye. It is calibrated and validated using 85–92-GHz passive microwave imagery because of this frequency’s relative ubiquity in TC applications; however, similar versions of ARCHER are also shown to work effectively with other satellite imagery of TCs. In TC cases with estimated low to moderate vertical wind shear, the accuracy (RMSE) of the ARCHER estimated center positions is 17 km (9 km for category 1–5 hurricanes). In cases with estimated high vertical shear, the accuracy of the ARCHER estimated center positions is 31 km (21 km for category 2–5 hurricanes).
Simulations of Subtropical Cyclones in a Baroclinic Channel Model
Authors: Davis Christopher A. 
Published: May 2010

Abstract
The present study considers a variety of cyclone developments that occur in an idealized, baroclinic channel model featuring full condensation heating effects over an ocean with prescribed sea surface temperature variation. The geostrophic basic-state jet is specified by the tropopause shape, and horizontal shear is included by specifying the meridional variation of zonal wind on the lower boundary. The horizontal shear induces anticyclonic wave breaking of baroclinic waves. Normal mode perturbations are computed using a “fake-dry” version of the model but integrated forward using full physics.
Low-latitude moist convection is particularly strong in simulations with strong surface easterlies that destabilize the troposphere through water vapor fluxes from the ocean surface. Deep convection produces a locally elevated dynamic tropopause and an associated anticyclone. This modified zonal flow supports moist baroclinic instability. The resulting cyclones, identified as subtropical cyclones, occur in deep westerly vertical wind shear but are nearly devoid of lower-tropospheric baroclinicity initially. These systems are distinguished from baroclinically dominated secondary cyclones that also form at relatively low latitudes in the simulations.
For weak jets and strong subtropical surface easterlies, subtropical cyclone development dominates formation on the midlatitude jet. For strong westerly jets or weak horizontal shear, the situation is reversed and the midlatitude baroclinic wave can help or hinder the ultimate intensification of the subtropical cyclone. The similarity of this cross-latitude influence to the extratropical transition of tropical cyclones is noted.