bluuebunny/crossref_metadata_2025_split huggingface dataset:
Freshwater acidification research in Atlantic Canada: a review of results and predictions for the future
Authors: Clair Thomas A. , Dennis Ian F. , Scruton David A. , Gilliss Mallory 
Published: January 2008

Atlantic Canada receives the lowest acid deposition amounts in eastern North America, but has some of the most acidic surface waters on the continent, due to the low buffering provided by regional bedrock and wetlands that produce natural organic acids. Southwestern and eastern parts of Nova Scotia combine poor buffering, high organic acidity, and higher acid deposition, to produce extremely low surface water pH and acid neutralization capacity (ANC) values. Although sulfate deposition is decreasing, concurrent reductions in dissolved base cations, as well as the acid-base characteristics of natural organic acids, are not allowing the recovery of ANC or surface water pH. Spring-time acid pulses occur in Atlantic Canada, though these have been reduced in severity with decreases in winter acid deposition, while autumnal low pH pulses caused by organic acids are a regular occurence in Nova Scotia and must be separated from mineral acidity pulses. Geochemical modeling using both critical load and dynamic approaches, nevertheless predict improvements in the water chemistry of Nova Scotia lakes within the next 20 years. However, re-establishment of pre-acidification water chemistry in most of its lakes will require greater reductions in S emissions than are currently planned in Canada and the United States.
CRYSTALLINE MAGNETOTUNNEL JUNCTIONS: Fe-MgO-Fe, Fe-FeOMgO-Fe and Fe-AuMgOAu-Fe
Authors: STILLING MORTEN 
Published: January 2008

We have modeled the electrical properties of three magnetotunnel junctions and find results similar to those in the literature. We have commenced investigations into the effects of perturbations to the exact positions of the atoms in these structures and report on the progress of these investigations. Note from Publisher: This article contains the abstract only.
TAp73α Increases p53 Tumor Suppressor Activity in Thyroid Cancer Cells via the Inhibition of Mdm2-Mediated Degradation
Authors: Malaguarnera Roberta , Vella Veronica , Pandini Giuseppe , Sanfilippo Mariangela , Pezzino Vincenzo , Vigneri Riccardo , Frasca Francesco 
Published: January 2008

Abstract
p53 family proteins include p53 tumor suppressor, p63, and p73. Despite the high similarity in structure and function with p53, p63, and p73 function in tumor suppression is still controversial. Here, we show that TAp73α, a transcriptionally active p73 isoform, is able to synergize p53 tumor suppressor function in thyroid cancer cells. Indeed, depletion of p73 by small interfering RNA in thyroid cancer cells resulted in a reduced transcriptional activity of p53. Ectopic coexpression of both p53 and TAp73α in thyroid cancer cells resulted in increased transcription and tumor suppressor function compared with p53 or TAp73α alone, as well as in increased p53 protein levels. The enhancing effect of TAp73α on p53 activity is Mdm2 dependent because it is prevented by Mdm2 depletion by small interfering RNA. At least two mechanisms may explain the interference of TAp73α with p53 function. First, in thyroid cancer cells, TAp73α inhibits the effect of p53 on Mdm2 induction by antagonizing p53 at the Mdm2 promoter level. Second, a TAp73α mutant (G264W), which is devoid of DNA binding capability, is still able to increase p53 protein levels by competing with p53 for Mdm2 protein binding. Taken together, these results indicate that in thyroid cancer cells, TAp73α is able to increase p53 protein level and function by interfering with Mdm2-mediated p53 degradation. These results may be useful for designing gene therapies aimed at restoring a normal p53 function in thyroid cancer cells. (Mol Cancer Res 2008;6(1):64–77)
Sensitivity of Normal, Paramalignant, and Malignant Human Urothelial Cells to Inhibitors of the Epidermal Growth Factor Receptor Signaling Pathway
Authors: MacLaine Nicola J. , Wood Michelle D. , Holder Julie C. , Rees Robert W. , Southgate Jennifer 
Published: January 2008

Abstract
Bladder cancer evolves via the accumulation of numerous genetic alterations, with loss of p53 and p16 function representing key events in the development of malignant disease. In addition, components of the epidermal growth factor receptor (EGFR) signaling pathway are frequently overexpressed, providing potential chemotherapeutic targets. We have previously described the generation of “paramalignant” human urothelial cells with disabled p53 or p16 functions. In this study, we investigated the relative responses of normal, paramalignant, and malignant human urothelial cells to EGFR tyrosine kinase inhibitors (PD153035 and GW572016), a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase (MEK) inhibitor (U0126), and a phosphatidylinositol 3-kinase inhibitor (LY294002). The proliferation of normal human urothelial cells was dependent on signaling via the EGFR and MEK pathways and was abolished reversibly by inhibitors of EGFR or downstream MEK signaling pathways. Inhibitors of phosphatidylinositol 3-kinase resulted in only transient cytostasis, which was most likely mediated via cross-talk with the MEK pathway. These responses were maintained in cells with disabled p16 function, whereas cells with loss of p53 function displayed reduced sensitivity to PD153035 and malignant cell lines were the most refractory to PD153035 and U0126. These results indicate that urothelial cells acquire insensitivity to inhibitors of EGFR signaling pathways as a result of malignant transformation. This has important implications for the use of EGFR inhibitors for bladder cancer therapy, as combination treatments with conventional chemotherapy or radiotherapy may protect normal cells and enable better selective targeting of malignant cells. (Mol Cancer Res 2008;6(1):53–63)
Histone Modifications at the ABCG2 Promoter following Treatment with Histone Deacetylase Inhibitor Mirror Those in Multidrug-Resistant Cells
Authors: To Kenneth K.W. , Polgar Orsolya , Huff Lyn M. , Morisaki Kuniaki , Bates Susan E. 
Published: January 2008

Abstract
ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is important in pharmacology and may play a role in stem cell biology and clinical drug resistance. To study the mechanism(s) regulating ABCG2 expression, we used ChIP to investigate the levels of acetylated histone H3, histone deacetylases (HDAC), histone acetyltransferases, and other transcription regulatory proteins associated with the ABCG2 promoter. Following selection for drug resistance and the subsequent overexpression of ABCG2, an increase in acetylated histone H3 but a decrease in class I HDACs associated with the ABCG2 promoter was observed. Permissive histone modifications, including an increase in histone H3 lysine 4 trimethylation (Me3-K4 H3) and histone H3 serine 10 phosphorylation (P-S10 H3), were observed accompanying development of the resistance phenotype. These changes mirrored those in some cell lines treated with a HDAC inhibitor, romidepsin. A repressive histone mark, trimethylated histone H3 lysine 9 (Me3-K9 H3), was found in untreated parental cells and cells that did not respond to HDAC inhibition with ABCG2 up-regulation. Interestingly, although all five studied cell lines showed global histone acetylation and MDR1 up-regulation upon HDAC inhibition, only those cells with removal of the repressive mark, and recruitment of RNA polymerase II and a chromatin remodeling factor Brg-1 from the ABCG2 promoter, showed increased ABCG2 expression. In the remaining cell lines, HDAC1 binding in association with the repressive Me3-K9 H3 mark apparently constrains the effect of HDAC inhibition on ABCG2 expression. These studies begin to address the differential effect of HDAC inhibitors widely observed in gene expression studies. (Mol Cancer Res 2008;6(1):151–64)
The Oncoprotein SS18-SSX1 Promotes p53 Ubiquitination and Degradation by Enhancing HDM2 Stability
Authors: D'Arcy Pádraig , Maruwge Wessen , Ryan Bríd Ann , Brodin Bertha 
Published: January 2008

Abstract
Mutations of the p53 gene are uncommon in synovial sarcoma, a high-grade tumor genetically characterized by the chromosomal translocation t:(X;18), which results in the fusion of SS18 with members of SSX gene family. Although implicated in tumorigenesis, the mechanisms by which SS18-SSX promotes tumor growth and cell survival are poorly defined. Here, we show that SS18-SSX1 negatively regulates the stability of the tumor suppressor p53 under basal conditions. Overexpression of SS18-SSX1 enhanced p53 ubiquitination and degradation in a manner dependent on the ubiquitin ligase activity of HDM2. The negative effect of SS18-SSX1 expression on p53 was mediated by its ability to promote HDM2 stabilization through inhibition of HDM2 autoubiquitination. Furthermore, SS18-SSX1 expression altered the induction of p53-regulated genes in response to cellular stress by abrogating the transactivation of HDM2, PUMA, and NOXA but not p21. Our data uncover a novel mechanism whereby SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2 and suggest that chemical compounds that target the p53-HDM2 regulatory axis may be of therapeutic benefit for the treatment of synovial sarcoma. (Mol Cancer Res 2008;6(1):127–38)
Lack of P-Glycoprotein Expression by Low-Dose Fractionated Radiation Results from Loss of Nuclear Factor-κB and NF-Y Activation in Oral Carcinoma Cells
Authors: Shareef Mohammed Momin , Brown Brandee , Shajahan Shahin , Sathishkumar Sabapathi , Arnold Susanne M. , Mohiuddin Mohammed , Ahmed Mansoor M. , Spring Paul M. 
Published: January 2008

Abstract
Multidrug resistance (MDR) is associated with the overproduction of the 170-kDa transmembrane protein P-glycoprotein (MDR1) caused by transcriptional activation. However, the activity of the MDR1 promoter in response to different doses of ionizing radiation has not been investigated. In this study, two squamous cell carcinoma oral cavity cell lines, T-167 and T-409, were exposed to either a standard clinical dose of 2 Gy or low-dose fractionated radiation therapy (LDFRT), delivered as 0.5 Gy in four fractions. MDR1 gene expression and degree of cell death were assessed. Clinically relevant 2-Gy dose of radiation resulted in increased expression of MDR1 by reverse transcription-PCR and luciferase reporter assays in both cell lines (T-167 and T-409), whereas LDFRT did not. LDFRT caused enhanced apoptosis when compared with the 2-Gy dose in T-167 and T-409 cells as assessed by terminal nucleotidyl transferase–mediated nick end labeling (TUNEL) assays. Transcription of the MDR1 gene is regulated by numerous transcription factors, which include nuclear factor-κB (NF-κB), NF-Y, SP1, YB1, MEF1 (MDR1 promoter-enhancing factor 1), p53, and NF-R1. Interestingly, 2 Gy robustly induced both NF-κB and NF-Y in T-167 and T-409 cells, but did not show induction when exposed to LDFRT. Silencing the expression of the DNA binding subunit of NF-κB, p50, by small interfering RNA vector resulted in a decrease of MDR1 function by rhodamine 123 efflux assay in T167 cells exposed to 2 Gy. Together, these results provide evidence for the lack of induction of P-glycoprotein expression by LDFRT, which has important implications in combinatorial cancer therapy, including the use of LDFRT as an adjuvant for chemotherapy. (Mol Cancer Res 2008;6(1):89–98)
Transcription-Dependent Epidermal Growth Factor Receptor Activation by Hepatocyte Growth Factor
Authors: Reznik Thomas E. , Sang Yingying , Ma Yongxian , Abounader Roger , Rosen Eliot M. , Xia Shuli , Laterra John 
Published: January 2008

AbstractThe mechanisms and biological implications of coordinated receptor tyrosine kinase coactivation remain poorly appreciated. Epidermal growth factor receptor (EGFR) and c-Met are frequently coexpressed in cancers, including those associated with hepatocyte growth factor (HGF) overexpression, such as malignant astrocytoma. In a previous analysis of the HGF-induced transcriptome, we found that two EGFR agonists, transforming growth factor-α and heparin-binding epidermal growth factor–like growth factor (HB-EGF), are prominently up-regulated by HGF in human glioma cells. We now report that stimulating human glioblastoma cells with recombinant HGF induces biologically relevant EGFR activation. EGFR phosphorylation at Tyr845 and Tyr1068 increased 6 to 24 h after cell stimulation with HGF and temporally coincided with the induction of transforming growth factor-α (∼5-fold) and HB-EGF (∼23-fold) expression. Tyr845 and Tyr1068 phosphorylation, in response to HGF, was inhibited by cycloheximide and actinomycin D, consistent with a requirement for DNA transcription and RNA translation. Specifically, blocking HB-EGF binding to EGFR with the antagonist CRM197 inhibited HGF-induced EGFR phosphorylation by 60% to 80% and inhibited HGF-induced S-G2-M transition. CRM197 also inhibited HGF-induced anchorage-dependent cell proliferation but had no effect on HGF-mediated cytoprotection. These findings establish that EGFR can be activated with functional consequences by HGF as a result of EGFR ligand expression. This transcription-dependent cross-talk between the HGF receptor c-Met and EGFR expands our understanding of receptor tyrosine kinase signaling networks and may have considerable consequences for oncogenic mechanisms and cancer therapeutics. (Mol Cancer Res 2008;6(1):139–50)
Acquisition of Stable Inducible Up-Regulation of Nuclear Factor-κB by Tumor Necrosis Factor Exposure Confers Increased Radiation Resistance without Increased Transformation in Breast Cancer Cells
Authors: Braunstein Steve , Formenti Silvia C. , Schneider Robert J. 
Published: January 2008

AbstractHigh-grade breast cancers are better adapted to hypoxia and more resistant to chemotherapy and radiotherapy. Constitutive activation of the transcription factor nuclear factor-κB (NF-κB) increases in breast tumors and in breast cancer cell lines, where it promotes chemoradiation resistance, in part by activation of antiapoptotic genes. The role for up-regulation of NF-κB in breast cancer progression is less clear. Here, we first show that whereas the constitutive activity of NF-κB is incrementally elevated from immortalized breast epithelial to frank transformed invasive ductal breast cancer cell lines (∼3-fold, ±0.1-fold, P &lt; 0.05), inflammatory cytokine-inducible activity is further increased (up to 9-fold, ±0.9-fold, P &lt; 0.05). We then show that inhibition of NF-κB activity selectively sensitizes transformed but not immortalized cells to killing by ionizing radiation or low levels of tumor necrosis factor (TNF) by up to 10-fold (±1-fold, P &lt; 0.05) but has little effect on hypoxia-mediated cell death. Prolonged cultivation of immortalized and partially transformed cells in TNF selected for cells displaying stable constitutive and strongly inducible overexpression of NF-κB even in the absence of TNF. Stable acquisition of increased NF-κB activity conferred resistance to ionizing radiation or inflammatory cytokines, which was dependent on elevated NF-κB activity, but had no effect on transformation potential measured by in vitro and in vivo parameters. Thus, TNF and possibly other inflammatory cytokines in the tumor-stroma matrix likely select for breast cancer cells that stably overexpress NF-κB, leading to greater cancer cell survival. Greater cell survival despite increased genomic injury may permit increased acquisition of malignant genetic alterations as well as resistance to chemoradiation therapy. (Mol Cancer Res 2008;6(1):78–88)
The Hydrological Cycle over a Wide Range of Climates Simulated with an Idealized GCM
Authors: O’Gorman Paul A. , Schneider Tapio 
Published: January 2008

Abstract
A wide range of hydrological cycles and general circulations was simulated with an idealized general circulation model (GCM) by varying the optical thickness of the longwave absorber. While the idealized GCM does not capture the full complexity of the hydrological cycle, the wide range of climates simulated allows the systematic development and testing of theories of how precipitation and moisture transport change as the climate changes. The simulations show that the character of the response of the hydrological cycle to variations in longwave optical thickness differs in different climate regimes.
The global-mean precipitation increases linearly with surface temperature for colder climates, but it asymptotically approaches a maximum at higher surface temperatures. The basic features of the precipitation–temperature relation, including the rate of increase in the linear regime, are reproduced in radiative–convective equilibrium simulations. Energy constraints partially account for the precipitation–temperature relation but are not quantitatively accurate.
Large-scale condensation is most important in the midlatitude storm tracks, and its behavior is accounted for using a stochastic model of moisture advection and condensation. The precipitation associated with large-scale condensation does not scale with mean specific humidity, partly because the condensation region moves upward and meridionally as the climate warms, and partly because the mean condensation rate depends on isentropic specific humidity gradients, which do not scale with the specific humidity itself.
The local water vapor budget relates local precipitation to evaporation and meridional moisture fluxes, whose scaling in the subtropics and extratropics is examined. A delicate balance between opposing changes in evaporation and moisture flux divergence holds in the subtropical dry zones. The extratropical precipitation maximum follows the storm track in warm climates but lies equatorward of the storm track in cold climates.
Analysis of Video Disdrometer and Polarimetric Radar Data to Characterize Rain Microphysics in Oklahoma
Authors: Cao Qing , Zhang Guifu , Brandes Edward , Schuur Terry , Ryzhkov Alexander , Ikeda Kyoko 
Published: January 2008

Abstract
In this paper, data from three 2-dimensional video disdrometers (2DVDs) and an S-band polarimetric radar are used to characterize rain microphysics in Oklahoma. Sampling errors from the 2DVD measurements are quantified through side-by-side comparisons. In an attempt to minimize the sampling errors, a method of sorting and averaging based on two parameters (SATP) is proposed. The shape–slope (μ–Λ) relation of a constrained gamma (C-G) model is then refined for the retrieval of drop size distributions (DSDs) from polarimetric radar measurements. An adjustable term that is based on observed radar reflectivity and differential reflectivity is introduced to make the C-G DSD model more applicable. Radar retrievals using this improved DSD model are shown to provide good agreement with disdrometer observations and to give reasonable results, including in locations near the leading edge of convection where poorly sampled large drops are often observed.
Mesoscale Model Initialization of the Fourier Method for Mountain Waves
Authors: Lindeman John , Boybeyi Zafer , Broutman Dave , Ma Jun , Eckermann Stephen D. , Rottman James W. 
Published: January 2008

Abstract
A Fourier method is combined with a mesoscale model to simulate mountain waves. The mesoscale model describes the nonlinear low-level flow and predicts the emerging wave field above the mountain. This solution serves as the lower boundary condition for the Fourier method, which follows the waves upward to much higher altitudes and downward to the ground to examine parameterizations for the orography and the lower boundary condition. A high-drag case with a Froude number of ⅔ is presented.
Interannual Variations of the Tropical Ocean Instability Wave and ENSO
Authors: An Soon-Il 
Published: January 2008

Abstract
Using ocean data assimilation products, variability of eastern Pacific Ocean tropical instability waves (TIWs) and their interaction with the El Niño–Southern Oscillation (ENSO) were analyzed. TIWs are known to heat the cold tongue through horizontal advection. Conversely, variability of the cold tongue influences TIW variability (TIWV). During La Niña, TIWs are more active and contribute to anomalous warming. During El Niño, TIWs are suppressed and induce an anomalous cooling. TIWV thus acts as negative feedback to ENSO. Interestingly, this feedback is stronger during La Niña than during El Niño. To investigate this negative/asymmetric feedback, a simple parameterization for the horizontal thermal flux convergence due to TIWs was incorporated into a simple ENSO model. The model results suggested that asymmetric thermal heating associated with TIWs can explain the El Niño–La Niña asymmetry (with larger-amplitude El Niños).
Seasonal Variation of the Seychelles Dome
Authors: Yokoi Takaaki , Tozuka Tomoki , Yamagata Toshio 
Published: January 2008

Abstract
Using an ocean general circulation model (OGCM), seasonal variation of the Seychelles Dome (SD) is investigated for the first time. The SD is an oceanic thermal dome located in the southwestern Indian Ocean, and its influence on sea surface temperature is known to play an important role in the Indian monsoon system. Its seasonal variation is dominated by a remarkable semiannual cycle resulting from local Ekman upwelling. This semiannual nature is explained by different contributions of the following two components of the Ekman pumping: one term that is proportional to the planetary beta and the zonal wind stress and the other term that is proportional to the wind stress curl. The former is determined by the seasonal change in the zonal component of the wind stress vector above the SD; it is associated with the Indian monsoon and causes downwelling (upwelling) during boreal summer (boreal winter). The latter, whose major contribution comes from the meridional gradient of the zonal wind stress, also shows a clear annual cycle with strong upwelling during boreal summer and fall. However, it remains almost constant for 5 months from June to October, even though the zonal wind stress itself varies significantly during this period.
The above overall feature is due to the unique location of the SD; it is located between the following two regions: one is dominated by the seasonal variation in wind stress resulting from the Indian monsoon, and the other is dominated by the southeasterly trade winds that prevail throughout a year. The above uniqueness provides a novel mechanism that causes the strong semiannual cycle in the tropical Indian Ocean.
Ocean Warming and Late-Twentieth-Century Sahel Drought and Recovery
Authors: Hagos Samson M. , Cook Kerry H. 
Published: January 2008

Abstract
The influences of decadal Indian and Atlantic Ocean SST anomalies on late-twentieth-century Sahel precipitation variability are investigated. The results of this regional modeling study show that the primary causes of the 1980s Sahel drought are divergence and anomalous anticyclonic circulation, which are associated with Indian Ocean warming. The easterly branch of this circulation drives moisture away from the Sahel. By competing for the available moisture, concurrent tropical Atlantic Ocean warming enhanced the areal coverage of the drought. The modeled partial recovery of the precipitation in the 1990s simulations is mainly related to the warming of the northern tropical Atlantic Ocean and an associated cyclonic circulation that supplies the Sahel with moisture. Because of the changes in the scale and distribution of the forcing, the divergence associated with the continued Indian Ocean warming during the 1990s was located over the tropical Atlantic, contributing to the recovery over the Sahel. In general, the influence of SSTs on Sahel precipitation is related to their modulation of the easterly flow and the associated moisture transport. Precipitation anomalies are further enhanced by the circulation patterns associated with local convergence anomalies. These convergence anomalies and circulation patterns are sensitive to the scale and distribution of the SST anomalies and the moisture.