bluuebunny/crossref_metadata_2025_split huggingface dataset:
EML4-ALKFusion Gene and Efficacy of an ALK Kinase Inhibitor in Lung Cancer
Authors: Koivunen Jussi P. , Mermel Craig , Zejnullahu Kreshnik , Murphy Carly , Lifshits Eugene , Holmes Alison J. , Choi Hwan Geun , Kim Jhingook , Chiang Derek , Thomas Roman , Lee Jinseon , Richards William G. , Sugarbaker David J. , Ducko Christopher , Lindeman Neal , Marcoux J. Paul , Engelman Jeffrey A. , Gray Nathanael S. , Lee Charles , Meyerson Matthew , Jänne Pasi A. 
Published: July 2008

AbstractPurpose: The EML4-ALK fusion gene has been detected in ∼7% of Japanese non-small cell lung cancers (NSCLC). We determined the frequency of EML4-ALK in Caucasian NSCLC and in NSCLC cell lines. We also determined whether TAE684, a specific ALK kinase inhibitor, would inhibit the growth of EML4-ALK-containing cell lines in vitro and in vivo.Experimental Design: We screened 305 primary NSCLC [both U.S. (n = 138) and Korean (n = 167) patients] and 83 NSCLC cell lines using reverse transcription-PCR and by exon array analyses. We evaluated the efficacy of TAE684 against NSCLC cell lines in vitro and in vivo.Results: We detected four different variants, including two novel variants, of EML4-ALK using reverse transcription-PCR in 8 of 305 tumors (3%) and 3 of 83 (3.6%) NSCLC cell lines. All EML4-ALK-containing tumors and cell lines were adenocarcinomas. EML4-ALK was detected more frequently in NSCLC patients who were never or light (&lt;10 pack-years) cigarette smokers compared with current/former smokers (6% versus 1%; P = 0.049). TAE684 inhibited the growth of one of three (H3122) EML4-ALK-containing cell lines in vitro and in vivo, inhibited Akt phosphorylation, and caused apoptosis. In another EML4-ALK cell line, DFCI032, TAE684 was ineffective due to coactivation of epidermal growth factor receptor and ERBB2. The combination of TAE684 and CL-387,785 (epidermal growth factor receptor/ERBB2 kinase inhibitor) inhibited growth and Akt phosphorylation and led to apoptosis in the DFCI032 cell line.Conclusions: EML4-ALK is found in the minority of NSCLC. ALK kinase inhibitors alone or in combination may nevertheless be clinically effective treatments for NSCLC patients whose tumors contain EML4-ALK.
Persistent Aberrations in Circulating DNA Integrity after Radiotherapy Are Associated with Poor Prognosis in Nasopharyngeal Carcinoma Patients
Authors: Chan K.C. Allen , Leung Sing-Fai , Yeung Sze-Wan , Chan Anthony T.C. , Lo Y.M. Dennis 
Published: July 2008

Abstract
Purpose: Aberrations of circulating nucleic acid integrity have been observed in cancer patients. However, the clinical significance of such changes has not been completely elucidated. In this study, we investigated the plasma DNA integrity in nasopharyngeal carcinoma (NPC) patients and its association with patients' survival after radiotherapy.
Experimental Design: Plasma DNA integrity was analyzed for 105 NPC patients before and after curative-intent radiotherapy and for 40 healthy controls. The plasma DNA concentration of each sample was measured by two real-time PCRs targeting the leptin gene. The amplicon sizes of the two assays were 105 and 201 bp. The integrity index was calculated as the ratio of the two concentrations (201 bp/105 bp). More intact circulating DNA would give a higher integrity index.
Results: The plasma DNA integrity index of the NPC patients was significantly higher than that of the healthy controls (median, 0.356 versus 0.238; P &lt; 0.001). After radiotherapy, a reduction in plasma DNA integrity index was observed in 70% NPC patients. Patients with persistent aberrations of plasma DNA integrity had significantly poorer survival probability than those with reduced DNA integrity after treatment (P &lt; 0.001, Kaplan-Meier).
Conclusions: NPC is associated with disturbances in the integrity of circulating cell-free DNA. The persistence of DNA integrity aberrations after radiotherapy is associated with reduced probability of disease-free survival. Therefore, the measurement of plasma DNA integrity may serve as a useful marker for the detection and monitoring of malignant diseases.
The Use of Chelated Radionuclide (Samarium-153-Ethylenediaminetetramethylenephosphonate) to Modulate Phenotype of Tumor Cells and Enhance T Cell–Mediated Killing
Authors: Chakraborty Mala , Wansley Elizabeth K. , Carrasquillo Jorge A. , Yu Sarah , Paik Chang H. , Camphausen Kevin , Becker Michael D. , Goeckeler William F. , Schlom Jeffrey , Hodge James W. 
Published: July 2008

Abstract
Purpose: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell–mediated killing.
Experimental Design: Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Fluorescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to 153Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to 153Sm-EDTMP rendered LNCaP cells more susceptible to T cell–mediated killing.
Results: Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class I (50%), and intercellular adhesion molecule-1 (40%) in response to 153Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to 153Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1.
Conclusions: Doses of 153Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that 153Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing.
Vaccination with a Recombinant Saccharomyces cerevisiae Expressing a Tumor Antigen Breaks Immune Tolerance and Elicits Therapeutic Antitumor Responses
Authors: Wansley Elizabeth K. , Chakraborty Mala , Hance Kenneth W. , Bernstein Michael B. , Boehm Amanda L. , Guo Zhimin , Quick Deborah , Franzusoff Alex , Greiner John W. , Schlom Jeffrey , Hodge James W. 
Published: July 2008

Abstract
Purpose: Saccharomyces cerevisiae, a nonpathogenic yeast, has been used previously as a vehicle to elicit immune responses to foreign antigens, and tumor-associated antigens, and has been shown to reduce tumor burden in mice. Studies were designed to determine if vaccination of human carcinoembryonic antigen (CEA)-transgenic (CEA-Tg) mice (where CEA is a self-antigen) with a recombinant S. cerevisiae construct expressing human CEA (yeast-CEA) elicits CEA-specific T-cell responses and antitumor activity.
Experimental Design: CEA-Tg mice were vaccinated with yeast-CEA, and CD4+ and CD8+ T-cell responses were assessed after one and multiple administrations or vaccinations at multiple sites per administration. Antitumor activity was determined by tumor growth and overall survival in both pulmonary metastasis and s.c. pancreatic tumor models.
Results: These studies demonstrate that recombinant yeast can break tolerance and that (a) yeast-CEA constructs elicit both CEA-specific CD4+ and CD8+ T-cell responses; (b) repeated yeast-CEA administration causes increased antigen-specific T-cell responses after each vaccination; (c) vaccination with yeast-CEA at multiple sites induces a greater T-cell response than the same dose given at a single site; and (d) tumor-bearing mice vaccinated with yeast-CEA show a reduction in tumor burden and increased overall survival compared to mock-treated or control yeast-vaccinated mice in both pulmonary metastasis and s.c. pancreatic tumor models.
Conclusions: Vaccination with a heat-killed recombinant yeast expressing the tumor-associated antigen CEA induces CEA-specific immune responses, reduces tumor burden, and extends overall survival in CEA-Tg mice. These studies thus form the rationale for the incorporation of recombinant yeast-CEA and other recombinant yeast constructs in cancer immunotherapy protocols.
Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence
Authors: Caruso Daniel J. , Carmack Adrienne J.K. , Lokeshwar Vinata B. , Duncan Robert C. , Soloway Mark S. , Lokeshwar Bal L. 
Published: July 2008

Abstract
Purpose: Lack of reliable biomarkers limits accurate prediction of prostate-specific antigen biochemical recurrence (disease progression) in prostate cancer. The two inflammatory chemokines, osteopontin and interleukin-8 (IL-8), are associated with tumor angiogenesis and metastasis. We investigated whether osteopontin and IL-8 expression in prostate cancer correlates with disease progression.
Experimental Design: Archival prostatectomy specimens (n = 103) were obtained from patients with minimum 72-month follow-up. Osteopontin and IL-8 expression was evaluated by immunohistochemistry and graded for intensity and the area. Association of osteopontin and IL-8 staining with biochemical recurrence was evaluated by univariate and multivariate models.
Results: In tumor cells, osteopontin and IL-8 staining was higher in the recurred group (203.2 ± 78.4; 181.1 ± 89.3) than in the nonrecurred group (122.7 ± 76.6; 96.4 ± 85.6; P &lt; 0.001). Higher osteopontin and IL-8 staining was also observed in benign areas adjacent to tumor in the recurred group, than in nonrecurred group. In univariate analysis, except age, all preoperative and postoperative variables and osteopontin and IL-8 staining scores were significantly associated with biochemical recurrence (P &lt; 0.05). In multivariate analysis, margin status and osteopontin staining independently associated with biochemical recurrence within 72 months. Osteopontin, either alone or with IL-8 and seminal vesicle invasion, was a significant variable in predicting biochemical recurrence within 24 months. Osteopontin and IL-8 staining predicted recurrence with high sensitivity (75.5%; 73.6%) and specificity (76%; 70.6%).
Conclusion: In prostatectomy specimens, osteopontin expression is independently associated with biochemical recurrence. Both osteopontin and IL-8 may be predictors of early disease progression.
Interaction between Coastal Upwelling and Local Winds at Cabo Frio, Brazil: An Observational Study
Authors: Franchito Sergio H. , Oda Tania O. , Rao V. Brahmananda , Kayano Mary T. 
Published: July 2008

Abstract
The relationships between coastal upwelling and local winds at Cabo Frio (Brazil) are studied using SST and time series of surface wind for a 10-yr period (1971–80). The results show that the seasonal variations of SST and local winds are closely related. Sea-breeze circulation is intensified by the enhancement of the land–sea temperature gradient due to cold water upwelling near the coast; coastal upwelling, in turn, is associated with strong northeasterlies. This result confirms the conclusions of earlier modeling studies. Interannual variability is also apparent in the results. During the period from 1971 to 1980, the highest SST values occur during the years 1972–73 (strong El Niño event) and the lowest occur in 1977 (moderate El Niño event). This suggests some possible effects of atmospheric teleconnections on South Atlantic SSTs. However, a record longer than 10 yr is needed to confirm the connection with El Niño and La Niña events. Time–frequency analyses of the SST and zonal wind series for 1975–77 are done using Morlet wavelet analysis. The global wavelet spectra for these variables show strong peaks at 24 and 157 h (approximately 6.6 days). These analyses also indicate that the sea breeze occurs at Cabo Frio almost year-round and confirm the relationships with the coastal upwelling in the region.
Strategies for Evaluating Quality Assurance Procedures
Authors: Durre Imke , Menne Matthew J. , Vose Russell S. 
Published: July 2008

Abstract
The evaluation strategies outlined in this paper constitute a set of tools beneficial to the development and documentation of robust automated quality assurance (QA) procedures. Traditionally, thresholds for the QA of climate data have been based on target flag rates or statistical confidence limits. However, these approaches do not necessarily quantify a procedure’s effectiveness at detecting true errors in the data. Rather, as illustrated by way of an “extremes check” for daily precipitation totals, information on the performance of a QA test is best obtained through a systematic manual inspection of samples of flagged values combined with a careful analysis of geographical and seasonal patterns of flagged observations. Such an evaluation process not only helps to document the effectiveness of each individual test, but, when applied repeatedly throughout the development process, it also aids in choosing the optimal combination of QA procedures and associated thresholds. In addition, the approach described here constitutes a mechanism for reassessing system performance whenever revisions are made following initial development.
Process-Oriented Analysis of Environmental Conditions Associated with Precipitation Fog Events in the New York City Region
Authors: Tardif Robert , Rasmussen Roy M. 
Published: July 2008

Abstract
An analysis of the environmental conditions associated with precipitation fog events is presented using 20 yr of historical observations taken in a region centered on New York, New York. The objective is to determine the preferred weather scenarios and identify physical processes influencing the formation of fog during precipitation. Salient synoptic-scale features are identified using NCEP–NCAR reanalyses. Local environmental parameters, such as wind speed and direction, temperature, and humidity, are analyzed using surface observations, while the vertical structure of the lower atmosphere is examined using available rawinsonde data. The analysis reveals that precipitation fog mostly occurs as a result of the gradual lowering of cloud bases as continuous light rain or light drizzle is observed. Such scenarios occur under various synoptic weather patterns in areas characterized by large-scale uplift, differential temperature advection, and positive moisture advection. Precipitation fog onset typically occurs with winds from the northeast at inland locations and onshore flow at coastal locations, with flows from the south to southwest aloft. A majority of the cases showed the presence of a sharp low-level temperature inversion resulting from differential temperature advection or through the interaction of warm air flowing over a cold surface in onshore flow conditions. This suggests a common scenario of fog formation under moistening conditions resulting from precipitation evaporating into colder air near the surface. A smaller number of events formed with cooling of the near-saturated or saturated air. Evidence is also presented of the possible role of shear-induced turbulent mixing in the production of supersaturation and fog formation during precipitation.
Does an August Singularity Exist in the Northern Rockies of the United States?
Authors: Soulé Peter T. , Knapp Paul A. 
Published: July 2008

Abstract
Climatic singularities offer a degree of orderliness to notable meteorological events that are typically characterized by significant temporal variability. Significant deviations from normal daily maximum temperatures that occur following the passage of a strong midlatitude cyclone in mid- to late August in the northern Rocky Mountains of the United States are recognized in the local culture as the “August Singularity.” Daily standardized maximum temperature anomalies for August–October were examined for eight climate stations in Montana and Idaho as indicators of major midlatitude storms. The data indicate that a single-day negative maximum temperature singularity exists for 13 August. Further, a 3-day singularity event exists for 24–26 August. It is concluded that the concept of an August Singularity in the northern Rockies is valid, because the high frequency of recorded negative maximum temperature anomalies suggests that there are specific time intervals during late summer that are more likely to experience a major midlatitude storm. The principal benefit to society for the August Singularity is that the reduced temperatures help in the efforts to control wildfires that are common this time of year in the northern Rockies.
The Impact of Aerosols on the Summer Rainfall Frequency in China
Authors: Choi Yong-Sang , Ho Chang-Hoi , Kim Jinwon , Gong Dao-Yi , Park Rokjin J. 
Published: July 2008

Abstract
The authors investigate the short-term relationship between aerosol concentrations and summer rainfall frequency in China using the daily surface observations of particulate matters with a diameter of less than 10 μm (PM10) mass concentration, rainfall, and satellite-observed cloud properties. Results in this study reveal that on the time scale of a few days aerosol concentration is positively correlated with the frequency of moderate-rainfall (10–20 mm day−1) days but is negatively correlated with the frequency of light-rainfall (&lt;5 mm day−1) days. Satellite observations of cloud properties show that higher aerosol concentrations are positively correlated with the increase in mixed cloud amount, cloud effective radius, cloud optical depth, and cloud-top heights; this corresponds to the decrease in low-level liquid clouds and the increase in midlevel ice–mixed clouds. Based on this analysis, the authors hypothesize that the increase in aerosol concentration results in the increase in summer rainfall frequency in China via enhanced ice nucleation in the midtroposphere. However, over the past few decades, observations show an increasing long-term trend in aerosol concentration but decreasing trends in summer rainfall frequency and relative humidity (RH) in China. Despite the short-term positive relationship between summer rainfall frequency and aerosol concentration found in this study, the long-term variations in summer rainfall frequency in China are mainly determined by other factors including RH variation possibly caused by global and regional climate changes. A continuous decrease in RH resulting in less summer rainfall frequency may further enhance aerosol concentrations in the future in conjunction with the increase in the anthropogenic emissions.
Coexistence of Equatorial Coupled Modes of ENSO*
Authors: Bejarano Luis , Jin Fei-Fei 
Published: July 2008

Abstract
To study the regimes of leading ocean–atmosphere coupled modes of relevance to the El Niño–Southern Oscillation (ENSO) phenomenon, a comprehensive eigenmode analysis of an intermediate coupled model linearized with respect to an array of basic states is performed. Different kinds of leading modes are found to coexist and become unstable under wide ranges of basic states and parameter conditions. In particular, the two most important modes have periods of around 4 and 2 yr. They are referred to as the quasi-quadrennial (QQ) and the quasi-biennial (QB) modes, respectively. The positive coupled feedback destabilizes and quantizes the near-continuous spectrum for the low-frequency modes of the upper-ocean dynamics, giving rise to these leading modes with distinct periodicities. The primary mechanism for the phase transition of the QQ mode is due to the slow oceanic dynamic adjustment of equatorial heat content, which is consistent with the simple conceptual recharge oscillator, whereas anomalous advection of sea surface temperature by equatorial zonal current anomalies plays a dominant role in the phase transition of the QB mode. The coexistence of these ENSO-like coupled modes under the present climate conditions may provide an explanation for the observed rich variations in ENSO behaviors.
On the Role of Atmospheric Teleconnections in Climate
Authors: Tsonis Anastasios A. , Swanson Kyle L. , Wang Geli 
Published: July 2008

Abstract
In a recent application of networks to 500-hPa data, it was found that supernodes in the network correspond to major teleconnection. More specifically, in the Northern Hemisphere a set of supernodes coincides with the North Atlantic Oscillation (NAO) and another set is located in the area where the Pacific–North American (PNA) and the tropical Northern Hemisphere (TNH) patterns are found. It was subsequently suggested that the presence of atmospheric teleconnections make climate more stable and more efficient in transferring information. Here this hypothesis is tested by examining the topology of the complete network as well as of the networks without teleconnections. It is found that indeed without teleconnections the network becomes less stable and less efficient in transferring information. It was also found that the pattern chiefly responsible for this mechanism in the extratropics is the NAO. The other patterns are simply a linear response of the activity in the tropics and their role in this mechanism is inconsequential.
Variability and Trend of North West Australia Rainfall: Observations and Coupled Climate Modeling
Authors: Shi Ge , Cai Wenju , Cowan Tim , Ribbe Joachim , Rotstayn Leon , Dix Martin 
Published: July 2008

Abstract
Since 1950, there has been an increase in rainfall over North West Australia (NWA), occurring mainly during the Southern Hemisphere (SH) summer season. A recent study using twentieth-century multimember ensemble simulations in a global climate model forced with and without increasing anthropogenic aerosols suggests that the rainfall increase is attributable to increasing Northern Hemisphere aerosols. The present study investigates the dynamics of the observed trend toward increased rainfall and compares the observed trend with that generated in the model forced with increasing aerosols.
It is found that the observed positive trend in rainfall is projected onto two modes of variability. The first mode is associated with an anomalously low mean sea level pressure (MSLP) off NWA instigated by the enhanced sea surface temperature (SST) gradients toward the coast. The associated cyclonic flows bring high-moisture air to northern Australia, leading to an increase in rainfall. The second mode is associated with an anomalously high MSLP over much of the Australian continent; the anticyclonic circulation pattern, over northern Australia, determines that when rainfall is anomalously high, west of 130°E, rainfall is anomalously low east of this longitude. The sum of the upward trends in these two modes compares well to the observed increasing trend pattern.
The modeled rainfall trend, however, is generated by a different process. The model suffers from an equatorial cold-tongue bias: the tongue of anomalies associated with El Niño–Southern Oscillation extends too far west into the eastern Indian Ocean. Consequently, there is an unrealistic relationship in the SH summer between Australian rainfall and eastern Indian Ocean SST: the rise in SST is associated with increasing rainfall over NWA. In the presence of increasing aerosols, a significant SST increase occurs in the eastern tropical Indian Ocean. As a result, the modeled rainfall increase in the presence of aerosol forcing is accounted for by these unrealistic relationships. It is not clear whether, in a model without such defects, the observed trend can be generated by increasing aerosols. Thus, the impact of aerosols on Australian rainfall remains an open question.