bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostaglandin E Receptor EP1 Suppresses Breast Cancer Metastasis and Is Linked to Survival Differences and Cancer Disparities
Authors: Ma Xinrong , Kundu Namita , Ioffe Olga B. , Goloubeva Olga , Konger Raymond , Baquet Claudia , Gimotty Phyllis , Reader Jocelyn , Fulton Amy M. 
Published: September 2010

Abstract
Cyclooxygenase-2 is frequently overexpressed and associated with poor prognosis in breast cancer. The cyclooxygenase-2 product prostaglandin E2 elicits cellular responses through four G-protein–coupled receptors, designated EP1 to EP4, coupled to distinct intracellular signaling pathways. EP4, expressed on malignant breast cells, promotes metastasis; however, a role for EP1 in metastasis has not been investigated. Using a murine model of metastatic breast cancer, we now show that pharmacologic antagonism of EP1 with SC19220 or AH6809 promoted lung colonization of mammary tumor cells by 3.7- to 5.4-fold. Likewise, reducing EP1 gene expression by shRNA also increased metastatic capacity relative to cells transfected with nonsilencing vector but did not affect the size of transplanted tumors. Examination of invasive ductal carcinomas by immunohistochemistry shows that EP1 was detected in both the cytoplasm and nucleus of benign ducts as well as malignant cells in some samples, but was absent or limited to either the nucleus or cytoplasm in other malignant samples. Overall survival for women with tumors that were negative for nuclear EP1 was significantly worse than for women with EP1 expression (P = 0.008). There was no difference in survival for women with differences in cytoplasmic EP1 expression (P = 0.46). Comparing EP1 mRNA in breast tumors from African American and European American women revealed that many more African American breast tumors lacked detectable EP1 mRNA (P = 0.04). These studies support the hypothesis that EP1 functions as a metastasis suppressor and that loss of nuclear EP1 is associated with poorer overall survival and may contribute to disparities in outcome in different populations. Mol Cancer Res; 8(10); 1310–8. ©2010 AACR.
Interactions of ErbB4 and Kap1 Connect the Growth Factor and DNA Damage Response Pathways
Authors: Gilmore-Hebert Maureen , Ramabhadran Rajani , Stern David F. 
Published: September 2010

Abstract
ErbB4 is unusual among receptor tyrosine kinases because some isoforms can be efficiently cleaved at the plasma membrane to release a soluble intracellular domain. The cleavage product has high kinase activity and homes to the nucleus. A screen for proteins that associate with the ErbB4 intracellular domain identified candidate interactors including ITCH, WWP2, Nucleolin, and Krab-associated protein 1 (Kap1). Kap1 binds to multiple isoforms of ErbB4 but does not require ErbB4 kinase activity for binding, nor is it an ErbB4 substrate. Kap1 reduces ERBB4 transcription and either directly or indirectly modulates the expression of genes that are themselves regulated by ErbB4. Upregulation of ErbB4 and suppression of MDM2 jointly enhance and accelerate the accumulation of p21CIP1 in response to DNA damage. Overall, these findings further substantiate the role of ErbB4 in conjoint regulation of growth factor signaling and DNA damage responses. Mol Cancer Res; 8(10); 1388–98. ©2010 AACR.
Patched1 Inhibits Epidermal Progenitor Cell Expansion and Basal Cell Carcinoma Formation by Limiting Igfbp2 Activity
Authors: Villani Rehan M. , Adolphe Christelle , Palmer James , Waters Michael J. , Wainwright Brandon J. 
Published: September 2010

Abstract
Basal cell carcinoma (BCC) of the skin is the most common form of cancer, with the majority being caused by mutations in the Patched1 (Ptch1) gene, leading to activation of the Hedgehog (Hh) signaling pathway. Hh signaling is implicated in many tumor types; thus, defining the mechanisms by which Ptch1 regulates tissue proliferation is of paramount importance. Here, we show that the key role of Ptch1 in the skin is to limit the size of the epidermal stem/progenitor compartment and allow hair follicle differentiation. Specifically, loss of Ptch1 leads to the promotion of progenitor cell fate by increasing basal cell proliferation and limiting the progression of basal cells into differentiated hair follicle cell types. Our data indicate that BCCs likely result from hair follicle progenitor cells that, due to Hh signal activation, cannot progress through normal hair follicle differentiation. These data confirm the role of Ptch1 as a negative regulator of epidermal progenitor turnover and also show for the first time that Ptch1 plays a role in the differentiation of the hair follicle lineage. In addition, we show that insulin-like growth factor binding protein 2 (Igfbp2) is upregulated in both murine and human BCCs and that blocking Igfbp2 activity reduces the Hh-mediated expansion of epidermal progenitor cells. We propose that Igfbp2 mediates epidermal progenitor cell expansion and therefore represents an epidermal progenitor cell–specific target of Hh signaling that promotes BCC development. Cancer Prev Res; 3(10); 1222–34. ©2010 AACR.
Dietary Vitamin D Exposure Prevents Obesity-Induced Increase in Endometrial Cancer inPten+/−Mice
Authors: Yu Wei , Cline Mark , Maxwell Larry G. , Berrigan David , Rodriguez Gustavo , Warri Anni , Hilakivi-Clarke Leena 
Published: September 2010

AbstractThe possibility that dietary vitamin D3 (VD3) exposure inhibits endometrial carcinogenesis in an animal model and modifies the enhanced risk of endometrial carcinoma associated with obesity was investigated. At 4 weeks of age, Pten+/− and wild-type mice were each divided into four treatment groups and fed AIN93G control diet, or AIN93G-based diet containing either 25,000 international units of VD3 per kilogram of diet, 58% fat to induce obesity (high fat), or high fat and 25,000 international units of VD3 per kilogram of diet. Mice were kept on these diets until they were sacrificed at week 28. Although VD3 did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial lesions. Specifically, high-fat diet increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet–fed Pten+/− mice to 78% in obese mice. Dietary VD3 decreased the incidence of endometrial pathology in obese Pten+/− mice to 25% (P &lt; 0.001). VD3 altered the endometrial expression of 25-hydroxylase, 1α-hydroxylase, and vitamin D receptor in the wild-type and Pten+/− mice. Estrogen receptor-α mRNA levels were higher (P &lt; 0.014) and progesterone receptor protein levels in the luminal epithelium were lower (P &lt; 0.04) in the endometrium of control diet–fed Pten+/− than wild-type mice, but the expression of these receptors was not affected by the dietary exposures. VD3 reversed the obesity-induced increase in osteopontin (P &lt; 0.001) and significantly increased E-cadherin expression (P &lt; 0.019) in the endometrium of obese Pten+/− mice. Our data confirm the known association between obesity and endometrial cancer risk. Dietary exposure to VD3 inhibited the carcinogenic effect of obesity on the endometrium. This protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin. Cancer Prev Res; 3(10); 1246–58. ©2010 AACR.
Skin Deep and Deeper: Multiple Pathways in Basal Cell Carcinogenesis
Authors: Peacock Craig D. , Rudin Charles M. 
Published: September 2010

Abstract
This perspective places the report by Villani et al. that appears in this issue of the journal (beginning on page 1222) in the context of recent work showing an intersection between two important developmental pathways implicated in oncogenesis: the hedgehog and insulin-like growth factor (IGF) pathways. Villani et al. define a key role for the IGF regulatory protein Igfbp2 in a genetic model of basal cell carcinogenesis driven by targeted constitutive activation of hedgehog signaling. Placed in the framework of other recently published work, the observations of Villani et al. both raise questions about the cell of origin for basal cell cancers and define additional putative therapeutic and preventive targets for this disease. Cancer Prev Res; 3(10); 1213–6. ©2010 AACR.
Molecular Conversations and the Development of the Hair Follicle and Basal Cell Carcinoma
Authors: Harris Pamela Jo , Takebe Naoko , Ivy S. Percy 
Published: September 2010

Abstract
The understanding of the anatomy and development of fetal and adult hair follicles and the molecular study of the major embryonic pathways that regulate the hair follicle have led to exciting discoveries concerning the development of basal cell carcinoma (BCC). These studies have shed light on the major roles of Sonic hedgehog (Shh) signaling and its interactions with the insulin-like growth factor (IGF) axis in BCC development. New work, for example, explores a link between Shh signaling and IGF binding protein-2 (IGFBP-2) in the hair follicle as it transforms into BCC. IGFBP-2 was overexpressed in specific hair follicle cells of mice with ectopically activated Shh signaling [keratin 14 (K14)-Cre: patched homologue 1 (Cre: Ptch1)lox/lox mice]. Ptch1 deletion resulted in both an expansion of the stem cell niche and inhibition of cell differentiation. In transformed hair follicles, IGFBP-2 mediates epidermal progenitor cell expansion. Evidence also indicated that IGFBP-2 is expressed in human BCC. Cancer Prev Res; 3(10); 1217–21. ©2010 AACR.
Adhesive Epicardial Corticosteroids Prevent Postoperative Atrial Fibrillation
Authors: Yoo Dale , Vinten-Johansen Jakob , Schmarkey L. Susan , Whalen S. Patrick , Bone C. Collin , Katzmark Sara L. , Langberg Jonathan 
Published: September 2010

Background—
Postoperative atrial fibrillation remains a common cause of morbidity. Although epicardial drug delivery can increase efficacy and reduce side effects, it is impractical for postoperative atrial fibrillation because pericardial bleeding/effusion and drainage cause rapid drug elimination. Fibrin glue sprayed on the epicardium is vigorously adherent, allowing an admixed drug to remain in contact with the heart. The purpose of the present study was to evaluate a novel corticosteroid-fibrin glue mixture applied to the atrial epicardium at the time of surgery for prevention of postoperative atrial tachyarrhythmias.

Methods and Results—

Talc was instilled into the pericardium in 15 dogs to simulate postoperative inflammation. Pacemakers were implanted to monitor arrhythmias. A mixture of triamcinolone and fibrin glue (Tisseel) was sprayed onto the atria of the treatment animals (n=9), whereas control animals (n=6) received Tisseel or nothing. After 1 week, pacemaker interrogation quantified postoperative atrial tachyarrhythmias (atrial rate >200 bpm) burden. Excised hearts underwent histological examination and tensile strength testing. postoperative atrial tachyarrhythmias occurred in 100% of control animals but only 33% of treatment animals (
P
=0.027). The median time (25th percentile, 75th percentile) in tachycardia was 5.5 hours (2.7, 12.6) per day in the control group, compared with 0 hours (0, 0.2) in the treatment group (
P
=0.001). Severe inflammation was present in 6 of 6 control animals and 1 of 9 treatment animals (
P
=0.001). The tensile strength of a healing left atriotomy was not significantly different between groups. Steroid levels at the time the animals were killed were very low (median of 0.22 μg/dL [0.18, 0.23]).

Conclusions—
A mixture of triamcinolone and fibrin glue sprayed onto the atria reduced postoperative atrial tachyarrhythmias and reduced inflammatory cell infiltration. There was no change in the tensile strength of a healing atriotomy and plasma steroid levels were low. Clinical trials of this approach are warranted.
Developments in Legal and Medical Practice Regarding the Unborn Child and the Need to Expand Prenatal Legal Protection
Authors: Dorscheidt Jozef 
Published: September 2010

AbstractDevelopments in legal and medical practice in the Netherlands give rise to questions regarding the legal position of the unborn child. This article provides an overview of these developments and argues — in view of developments in other countries — that current Dutch legislation regarding the unborn child is not up to date. In effect, the article challenges the idea that the actual legal protection of the unborn child under positive Dutch law can be considered proportionate, even sufficient. To support this view the author will show that abortion is not the only matter in which clarity as to the legal protection of the viable unborn child is required. This signalisation provides good cause to reconsider the Dutch perspective on the matter, thus offering a point of reference to countries with a similar interpretation of what constitutes an appropriate legal protection of the unborn child.
Danish Cartoons and Christian-Muslim Relations in Denmark
Authors: Nielsen Jørgen S. 
Published: September 2010

AbstractPrior to the arrival of Muslim immigrants and refugees into Denmark in the 1970s and after, Denmark’s experience with Islam was partly through university-based research and partly through missionary activities. During the 1980s and 1990s both sectors gradually adapted to the settlement of Muslims in the country. In the 1990s the public political debate became increasingly heated, leading to a steady tightening of immigration and refugee policies. In this debate an Islamic dimension was starkly exacerbated by the events of 11 September 2001 and the arrival of a new centre-right government two months later. This was the environment in which the ‘Muhammad cartoons’ were published in September 2005, and in which the domestic and international crisis played out over the subsequent 6-8 months. But the events also encouraged the emergence of new Islamic organizations and new responses, both negative and positive, on the part of the churches. While the sharp public debate continues, new apparently sustainable structures of Christian-Muslim relations have appeared.
Inter-Faith Relations in Britain Since 1970 — An Assessment
Authors: Siddiqui Ataullah 
Published: September 2010

AbstractThis article argues that inter-faith relations in Britain are essentially inspired by the existential realities of a multi-cultural and multi-religious society. It argues that the earliest formal discussions between the followers of various faiths were motivated by their desire to ‘understand’ the beliefs and practices of other faiths. However these ‘engagements’ were confined to local and national secular civic bodies. The motivations behind these ‘engagements’ were essentially need-oriented rather than driven by religious motives. It also seems that the interest of successive British governments was to manage the migrant communities through an agenda based on ‘ethnicity’ and ‘race’ and the religious needs of these migrant communities were largely defined within that context. More recently the British state found it necessary to involve itself directly by funding projects of inter-faith nature. Churches, mainly the Church of England, have become over the years the mediator between the ‘migrant communities’ and the state. This ‘mediation’ is motivated by the churches’ evangelical outreach but also by humanitarian reasons. Due to internal and external factors, all three actors have, over the years, changed and adapted their positions considerably.
Flow and Turbulence in an Urban Canyon
Authors: Zajic D. , Fernando H. J. S. , Calhoun R. , Princevac M. , Brown M. J. , Pardyjak E. R. 
Published: September 2010

Abstract
A better understanding of the interaction between the built environment and the atmosphere is required to more effectively manage urban airsheds. This paper reports an analysis of data from an atmospheric measurement campaign in Oklahoma City, Oklahoma, during the summer of 2003 that shows wind flow patterns, turbulence, and thermal effects in the downtown area. Experimental measurements within a street canyon yielded airflow patterns, stability conditions, and turbulence properties as a function of the incoming wind direction and time of the day. Air and surface temperatures at two different sites, one within the downtown urban canyon and the other in a nearby park, were measured. A study of the stability conditions within the urban canyon during the campaign indicates that dynamically stable conditions did not occur within the canyon. This provides evidence that the built environment can strongly influence the thermal characteristics in cities. Mean flow patterns close to the street level are analyzed for two different ranges of incoming wind directions and are compared with those obtained from a previous field experiment featuring idealized building configurations. This paper presents an approach allowing the estimation of wind direction in an urban canyon, given inflow conditions, that shows good agreement with wind patterns in the Oklahoma City street canyon. Turbulence statistics were calculated and normalized using different velocity scales to investigate the efficacy of the latter in specifying turbulence levels in urban canopies. The dependence of turbulence quantities on incoming wind direction and time of the day was investigated.
Helical Turbulence Prevails over Inertial Waves in Forced Rotating Flows at High Reynolds and Low Rossby Numbers
Authors: Baerenzung Julien , Rosenberg D. , Mininni P. D. , Pouquet A. 
Published: September 2010

Abstract
A study of spectral laws for helical turbulence in the presence of solid body rotation up to Reynolds numbers Re ~ 1 × 105 and down to Rossby numbers Ro ~ 3 × 10−3 is presented. The forcing function is a fully helical flow that can also be viewed as mimicking the effect of atmospheric convective motions. Variants of a model developed previously by Baerenzung et al. are tested in the helical case against direct numerical simulation (DNS), using data from a run on a grid of 15363 points; its efficiency is also contrasted against a spectral large-eddy simulation (LES) by Chollet and Lesieur, as well as an underresolved DNS. The model including the contribution of helicity to the spectral eddy dissipation and eddy noise behaves best, allowing the recovery of statistical features of the flow. Even if the model is based on isotropic assumptions, the authors demonstrated in a previous study that the small scales of flows at moderate Rossby number can be considered to be isotropic in the range of parameters considered here and that therefore their model is appropriate to treat this kind of flow.
An exploration of parameter space is then performed beyond what is feasible today using DNS. At a fixed Reynolds number, lowering the Rossby number leads to a regime of wave-mediated inertial helicity cascades to small scales. However, at a fixed Rossby number, increasing the Reynolds number leads the system to be dominated by turbulent energy exchanges where the role of inertial waves is to weaken the direct cascade of energy while strengthening the large scales. It is found that a useful parameter for partitioning the data is , with Urms, ν, and Ω being the rms velocity, the viscosity, and the rotation rate, respectively. The parameter that determines how much the energy cascade is direct or inverse—in which case the cascade to small scales is predominantly that of helicity—is linked to Ro.
Effective Radius of Ice Particles in Cirrus and Contrails
Authors: Schumann U. , Mayer B. , Gierens K. , Unterstrasser S. , Jessberger P. , Petzold A. , Voigt C. , Gayet J-F. 
Published: September 2010

Abstract
This paper discusses the ratio C between the volume mean radius and the effective radius of ice particles in cirrus and contrails. The volume mean radius is proportional to the third root of the ratio between ice water content and number of ice particles, and the effective radius measures the ratio between ice particle volume and projected cross-sectional area. For given ice water content and number concentration of ice particles, the optical depth scales linearly with C. Hence, C is an important input parameter for radiative forcing estimates. The ratio C in general depends strongly on the particle size distribution (PSD) and on the particle habits. For constant habits, C can be factored into a PSD and a habit factor. The PSD factor is generally less than one, while the habit factor is larger than one for convex or concave ice particles with random orientation. The value of C may get very small for power-law PSDs with exponent n between −4 and 0, which is often observed. For such PSDs, most of the particle volume is controlled by a few large particles, while most of the cross-sectional area is controlled by the many small particles. A new particle habit mix for contrail cirrus including small droxtal-shape particles is suggested. For measured cirrus and contrails, the dependence of C on volume mean particle radius, ambient humidity, and contrail age is determined. For cirrus, C varies typically between 0.4 and 1.1. In contrails, C = 0.7 ± 0.3, with uncertainty ranges increasing with the volume radius and contrail age. For the small particles in young contrails, the extinction efficiency in the solar range deviates considerably from the geometric optics limit.
Excitation of Intraseasonal Variability in the Equatorial Atmosphere by Yanai Wave Groups via WISHE-Induced Convection
Authors: Solodoch Aviv , Boos William R. , Kuang Zhiming , Tziperman Eli 
Published: September 2010

Abstract
A mechanism is presented, based on multiscale interactions via nonlinear wind-induced surface heat exchange (WISHE), that produces eastward-propagating, intraseasonal convective anomalies in the tropical atmosphere. Simulations of convectively coupled disturbances are presented in two intermediate-complexity atmospheric models. One is a shallow water model with a simple WISHE-motivated heating term. The other model is also based on a first baroclinic mode but has an additional prognostic equation for humidity and a simple representation of moist convection based on a quasi-equilibrium approximation. In spite of many differences between the models, they robustly produce a coherent signal in westerly winds and convection that travels eastward at 4–10 m s−1. It is shown here that this slow signal is a forced response to an eastward-propagating Yanai (mixed Rossby–gravity) wave group. The response takes the form of a forced Kelvin wave that is driven nonlinearly, via WISHE, by meridional wind anomalies of the Yanai wave group and that travels considerably more slowly than the free convectively coupled Kelvin waves in these models. The Yanai waves are destabilized in the models used here by WISHE in the presence of mean easterlies, but more generally they could also be excited by stratiform instability in the absence of mean easterlies so that the mechanism described here could also operate without mean easterlies. Similarities to and differences from the Madden–Julian oscillation (MJO) and convectively coupled tropical waves are discussed.