bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sampling with replacement in occupancy studies with spatial replication
Authors: Guillera‐Arroita Gurutzeta 
Published: February 2011

Summary 1. The proportion of sites occupied by a species is a state variable commonly used in ecology. Replicate surveys at sampled sites can be used to address the problem of imperfect detection to obtain an asymptotically unbiased estimator of species occupancy. Replication can be achieved in various ways, including visiting a series of spatial subunits within each surveyed site. Depending on how these spatial subunits are sampled, bias can be induced in the estimator of site occupancy. 2. This paper explores and discusses the consequences of sampling with or without replacement when using spatial replication in occupancy studies and the species is absent from some of the replicates within occupied sites. Simulations are used to illustrate the findings, and results are compared with previously published recommendations. 3. The study shows that sampling without replacement does not induce bias in the estimator of site occupancy when each spatial subunit has a constant probability of occupancy, regardless of the occupancy status of other subunits within the same sampling site. 4. The study further demonstrates that sampling with replacement may in this case induce bias in the site occupancy estimator. It is thus argued that choosing to sample with or without replacement should be based on considerations of the system in question. 5. Synthesis and applications: In some occupancy studies, it may be convenient to obtain the replication required to account for imperfect detection by surveying various spatial subunits within each sampling site. Sampling with replacement has previously been recommended for this scenario. However, this sampling strategy can induce bias in the estimator of occupancy under realistic ecological conditions. The discussion provided here is of special interest for those involved in the design of occupancy studies.
On two examples by Iyama and Yoshino
Authors: Keller Bernhard , Murfet Daniel , Bergh Michel Van den 
Published: February 2011

AbstractIn a recent paper, Iyama and Yoshino considered two interesting examples of isolated singularities over which it is possible to classify the indecomposable maximal Cohen–Macaulay modules in terms of linear algebra data. In this paper, we present two new approaches to these examples. In the first approach we give a relation with cluster categories. In the second approach we use Orlov’s result on the graded singularity category.
Serre weights for quaternion algebras
Authors: Gee Toby , Savitt David 
Published: February 2011

AbstractWe study the possible weights of an irreducible two-dimensional mod p representation of ${\rm Gal}(\overline {F}/F)$ which is modular in the sense that it comes from an automorphic form on a definite quaternion algebra with centre F which is ramified at all places dividing p, where F is a totally real field. In most cases we determine the precise list of possible weights; in the remaining cases we determine the possible weights up to a short and explicit list of exceptions.
A Generalized Hybrid Steepest-Descent Method for Variational Inequalities in Banach Spaces
Authors: Sahu D. R. , Wong N. C. , Yao J. C. 
Published: February 2011

AbstractThe hybrid steepest-descent method introduced by Yamada (2001) is an algorithmic solution to the variational inequality problem over the fixed point set of nonlinear mapping and applicable to a broad range of convexly constrained nonlinear inverse problems in real Hilbert spaces. Lehdili and Moudafi (1996) introduced the new prox-Tikhonov regularization method for proximal point algorithm to generate a strongly convergent sequence and established a convergence property for it by using the technique of variational distance in Hilbert spaces. In this paper, motivated by Yamada's hybrid steepest-descent and Lehdili and Moudafi's algorithms, a generalized hybrid steepest-descent algorithm for computing the solutions of the variational inequality problem over the common fixed point set of sequence of nonexpansive-type mappings in the framework of Banach space is proposed. The strong convergence for the proposed algorithm to the solution is guaranteed under some assumptions. Our strong convergence theorems extend and improve certain corresponding results in the recent literature.
Tumor Suppressor RARRES1 Interacts with Cytoplasmic Carboxypeptidase AGBL2 to Regulate the α-Tubulin Tyrosination Cycle
Authors: Sahab Ziad J. , Hall Michael D. , Me Sung You , Dakshanamurthy Sivanesan , Ji Yun , Kumar Deepak , Byers Stephen W. 
Published: February 2011

Abstract
Even though it is among the most commonly methylated loci in multiple cancers, the retinoic acid–induced tumor suppressor retinoic acid receptor responder 1 (RARRES1) has no known function. We now show that RARRES1 is lost in many cancer cells, particularly those with a mesenchymal phenotype, and is a transmembrane carboxypeptidase inhibitor that interacts with ATP/GTP binding protein-like 2 (AGBL2), a cytoplasmic carboxypeptidase. Knockdown of AGBL2 results in a failure of the cell to detyrosinate the C-terminal EEY region of α-tubulin and indicates that it is a candidate for the long sought-after tubulin tyrosine carboxypeptidase important in the regulation of microtubule dynamics. In contrast, knockdown of RARRES1 increases the level of detyrosinated α-tubulin consistent with a role as the cognate inhibitor of AGBL2. We conclude that RARRES1, its interacting partners AGBL2, Eg5/KIF11, another EEY-bearing protein (EB1), and the microtubule tyrosination cycle are important in tumorigenesis and identify a novel area for therapeutic intervention. Cancer Res; 71(4); 1219–28. ©2011 AACR.
HIF-1α Confers Aggressive Malignant Traits on Human Tumor Cells Independent of Its Canonical Transcriptional Function
Authors: Yoo Young-Gun , Christensen Jared , Huang L. Eric 
Published: February 2011

Abstract
Hypoxia is known to favor tumor survival and progression. Numerous studies have shown that hypoxia-inducible factor 1α (HIF-1α), an oxygen-sensitive transcription factor, is overexpressed in various types of human cancers and upregulates a battery of hypoxia-responsive genes for the growth and survival of cancer cells. Although tumor progression involves the acquisition of genetic and/or epigenetic changes that confer additional malignant traits, the underlying mechanisms of these changes remain obscure. We recently identified an alternative mechanism of HIF-1α function by which HIF-1α suppresses DNA repair by counteracting c-Myc transcriptional activity that maintains gene expression. Here, we show that this HIF-α–c-Myc pathway plays an essential role in mediating hypoxic effects on malignant progression via genetic alterations, resulting in the formation of malignant tumors with aggressive local invasion and epithelial–mesenchymal transition. We show an absolute requirement of the HIF-α–c-Myc pathway for malignant progression, whereas the canonical transcription function of HIF-1α alone is insufficient and seemingly dispensable. This study indicates that HIF-1α induction of genetic alteration is the underlying cause of tumor progression, especially by the hypoxic microenvironment. Cancer Res; 71(4); 1244–52. ©2011 AACR.
Small Molecule Kinase Inhibitor Screen Identifies Polo-Like Kinase 1 as a Target for Neuroblastoma Tumor-Initiating Cells
Authors: Grinshtein Natalie , Datti Alessandro , Fujitani Mayumi , Uehling David , Prakesch Michael , Isaac Methvin , Irwin Meredith S. , Wrana Jeffrey L. , Al-awar Rima , Kaplan David R. 
Published: February 2011

Abstract
Neuroblastoma (NB) is an often fatal pediatric tumor of neural crest origin. We previously isolated NB tumor-initiating cells (NB TIC) from bone marrow metastases that resemble cancer stem cells and form metastatic NB in immunodeficient animals with as few as ten cells. To identify signaling pathways important for the survival and self-renewal of NB TICs and potential therapeutic targets, we screened a small molecule library of 143 protein kinase inhibitors, including 33 in clinical trials. Cytostatic or cytotoxic drugs were identified that targeted PI3K (phosphoinositide 3-kinase)/Akt, PKC (protein kinase C), Aurora, ErbB2, Trk, and Polo-like kinase 1 (PLK1). Treatment with PLK1 siRNA or low nanomolar concentrations of BI 2536 or BI 6727, PLK1 inhibitors in clinical trials for adult malignancies, were cytotoxic to TICs whereas only micromolar concentrations of the inhibitors were cytotoxic for normal pediatric neural stem cells. Furthermore, BI 2536 significantly inhibited TIC tumor growth in a therapeutic xenograft model, both as a single agent and in combination with irinotecan, an active agent for relapsed NB. Our findings identify candidate kinases that regulate TIC growth and survival and suggest that PLK1 inhibitors are an attractive candidate therapy for metastatic NB. Cancer Res; 71(4); 1385–95. ©2011 AACR.
Replication and Functional Genomic Analyses of the Breast Cancer Susceptibility Locus at 6q25.1 Generalize Its Importance in Women of Chinese, Japanese, and European Ancestry
Authors: Cai Qiuyin , Wen Wanqing , Qu Shimian , Li Guoliang , Egan Kathleen M. , Chen Kexin , Deming Sandra L. , Shen Hongbing , Shen Chen-Yang , Gammon Marilie D. , Blot William J. , Matsuo Keitaro , Haiman Christopher A. , Khoo Ui Soon , Iwasaki Motoki , Santella Regina M. , Zhang Lina , Fair Alecia Malin , Hu Zhibin , Wu Pei-Ei , Signorello Lisa B. , Titus-Ernstoff Linda , Tajima Kazuo , Henderson Brian E. , Chan Kelvin Y.K. , Kasuga Yoshio , Newcomb Polly A. , Zheng Hong , Cui Yong , Wang Furu , Shieh Ya-Lan , Iwata Hiroji , Le Marchand Loic , Chan Sum Yin , Shrubsole Martha J. , Trentham-Dietz Amy , Tsugane Shoichiro , Garcia-Closas Montserrat , Long Jirong , Li Chun , Shi Jiajun , Huang Bo , Xiang Yong-Bing , Gao Yu-Tang , Lu Wei , Shu Xiao-Ou , Zheng Wei 
Published: February 2011

Abstract
We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22–1.38) and 1.64 (1.50–1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10−30], Japanese women [ORs (95% CI) = 1.31 (1.13–1.52) and 1.37 (1.06–1.76), P for trend = 2.51 × 10−4], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99–1.16) and 1.18 (1.04–1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63–1.06) and 0.85 (0.65–1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r2 = 0.91) and European-ancestry (r2 = 0.83) populations, but not in Africans (r2 = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. Cancer Res; 71(4); 1344–55. ©2011 AACR.
Pten in the Breast Tumor Microenvironment: Modeling Tumor–Stroma Coevolution
Authors: Wallace Julie A. , Li Fu , Leone Gustavo , Ostrowski Michael C. 
Published: February 2011

Abstract
Solid human tumors and their surrounding microenvironment are hypothesized to coevolve in a manner that promotes tumor growth, invasiveness, and spread. Mouse models of cancer have focused on genetic changes in the epithelial tumor cells and therefore have not robustly tested this hypothesis. We have recently developed a murine breast cancer model that ablates the PTEN tumor suppressor pathway in stromal fibroblasts. Remarkably, the model resembles human breast tumors both at morphologic and molecular levels. We propose that such models reflect subtypes of tumor–stromal coevolution relevant to human breast cancer, and will therefore be useful in defining the mechanisms that underpin tumor–stroma cross-talk. Additionally, these models should also aid in molecularly classifying human breast tumors on the basis of both the microenvironment subtypes they contain as well as on the tumor subtype. Cancer Res; 71(4); 1203–7. ©2011 AACR.
Knockdown of Oncogenic KRAS in Non–Small Cell Lung Cancers Suppresses Tumor Growth and Sensitizes Tumor Cells to Targeted Therapy
Authors: Sunaga Noriaki , Shames David S. , Girard Luc , Peyton Michael , Larsen Jill E. , Imai Hisao , Soh Junichi , Sato Mitsuo , Yanagitani Noriko , Kaira Kyoichi , Xie Yang , Gazdar Adi F. , Mori Masatomo , Minna John D. 
Published: February 2011

Abstract
Oncogenic KRAS is found in more than 25% of lung adenocarcinomas, the major histologic subtype of non–small cell lung cancer (NSCLC), and is an important target for drug development. To this end, we generated four NSCLC lines with stable knockdown selective for oncogenic KRAS. As expected, stable knockdown of oncogenic KRAS led to inhibition of in vitro and in vivo tumor growth in the KRAS-mutant NSCLC cells, but not in NSCLC cells that have wild-type KRAS (but mutant NRAS). Surprisingly, we did not see large-scale induction of cell death and the growth inhibitory effect was not complete. To further understand the ability of NSCLCs to grow despite selective removal of mutant KRAS expression, we conducted microarray expression profiling of NSCLC cell lines with or without mutant KRAS knockdown and isogenic human bronchial epithelial cell lines with and without oncogenic KRAS. We found that although the mitogen-activated protein kinase pathway is significantly downregulated after mutant KRAS knockdown, these NSCLCs showed increased levels of phospho-STAT3 and phospho–epidermal growth factor receptor, and variable changes in phospho-Akt. In addition, mutant KRAS knockdown sensitized the NSCLCs to p38 and EGFR inhibitors. Our findings suggest that targeting oncogenic KRAS by itself will not be sufficient treatment, but may offer possibilities of combining anti-KRAS strategies with other targeted drugs. Mol Cancer Ther; 10(2); 336–46. ©2011 AACR.
Atypical Protein Kinase Cι (PKCι) Promotes Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing Resistance to Anoikis via PKCι-SKP2-AKT Pathway
Authors: Liu Shu-Guang , Wang Bo-Shi , Jiang Yan-Yi , Zhang Tong-Tong , Shi Zhi-Zhou , Yang Yang , Yang Yi-Ling , Wang Xiao-Chun , Lin De-Chen , Zhang Yu , Yang Hai , Cai Yan , Zhan Qi-Min , Wang Ming-Rong 
Published: February 2011

Abstract
Protein kinase Cι (PKCι) is an atypical PKC isoform and participates in multiple aspects of the transformed phenotype in human cancer cells. We previously reported that frequent amplification and overexpression of PKCι were correlated with lymph node metastasis in primary esophageal squamous cell carcinomas (ESCC). In the present study, short interfering RNA–mediated silencing of PKCι revealed that this enzyme was required for cell migration, invasion, and resistance to anoikis. In vivo experiments showed that PKCι suppression decreased tumor growth in esophageal cancer xenografts and lung metastases in nude mice. At the molecular level, knockdown of PKCι in suspended ESCC cells caused a decrease in S-phase kinase-associated protein 2 (SKP2) that had been reported to promote resistance to anoikis via the PI3K/AKT pathway. AKT phosphorylation was abolished after PKCι suppression, but AKT activation could be refreshed by PKCι upregulation, suggesting that PKCι enhanced cell resistance to anoikis via the PKCι-SKP2-PI3K/AKT pathway. Addition of the proteasome inhibitor MG132 prevented the decrease of SKP2 in PKCι silenced cells, and polyubiquitin-SKP2 was elevated after PKCι depletion, showing that PKCι might regulate the expression of SKP2 through the ubiquitin-proteasome pathway in suspended cells. Furthermore, overexpression of SKP2 in PKCι-downregulated cells restored cell resistance to anoikis. Most importantly, PKCι expression significantly correlated with SKP2 in 133 ESCC tissues (P = 0.031). Taken together, our data show that PKCι promotes tumorigenicity and metastasis of human esophageal cancer and that SKP2 is a candidate downstream effector of PKCι signaling in ESCC. Mol Cancer Res; 9(4); 390–402. ©2011 AACR.
Roles of Prostaglandin E
2
–EP3/EP4 Receptor Signaling in the Enhancement of Lymphangiogenesis During Fibroblast Growth Factor-2–Induced Granulation Formation
Authors: Hosono Kanako , Suzuki Tatsunori , Tamaki Hideaki , Sakagami Hiroyuki , Hayashi Izumi , Narumiya Shuh , Alitalo Kari , Majima Masataka 
Published: February 2011

Objective—

One of the hallmarks of inflammation is lymphangiogesis that drains the interstitial fluids. During chronic inflammation, angiogenesis is induced by a variety of inflammatory mediators, such as prostaglandins (PGs). However, it remains unknown whether they enhance lymphangiogenesis. We examined the roles of cyclooxygenase-2 (COX-2) and PGE
2
receptor signaling in enhancement of lymphangiogenesis during proliferative inflammation.

Methods and Results—

Lymphangiogenesis estimated by podoplanin/vascular endothelial growth factor (VEGF) receptor-3/LYVE-1 expression was upregulated during proliferative inflammation seen around and into subcutaneous Matrigel plugs containing fibroblast growth factor-2 (125 ng/site). A COX-2 inhibitor (celecoxib) significantly reduced lymphangiogenesis in a dose-dependent manner, whereas topical PGE
2
enhanced lymphangiogenesis. Topical injection of fluorescein isothiocyanate–dextran into the Matrigel revealed that lymphatic flow from the Matrigels was COX-2 dependent. Lymphangiogenesis was suppressed in the granulation tissues of mice lacking either EP3 or EP4, suggesting that these molecules are receptors in response to endogenous PGE
2
. An EP3-selective agonist (ONO-AE-248) increased the expression of VEGF-C and VEGF-D in cultured macrophages, whereas an EP4-selective agonist (ONO-AE1-329) increased VEGF-C expression in cultured macrophages and increased VEGF-D expression in cultured fibroblasts.

Conclusion—
Our findings suggest that COX-2 and EP3/EP4 signaling contributes to lymphangiogenesis in proliferative inflammation, possibly via induction of VEGF-C and VEGF-D, and may become a therapeutic target for controlling lymphangiogenesis.
Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide
Authors: Richards Jennifer M.J. , Semple Scott I. , MacGillivray Thomas J. , Gray Calum , Langrish Jeremy P. , Williams Michelle , Dweck Marc , Wallace William , McKillop Graham , Chalmers Roderick T.A. , Garden O. James , Newby David E. 
Published: February 2011

Background—
Abdominal aortic aneurysms are a major cause of death. Prediction of aneurysm expansion and rupture is challenging and currently relies on the simple measure of aneurysm diameter. Using MRI, we aimed to assess whether areas of cellular inflammation correlated with the rate of abdominal aortic aneurysm expansion.

Methods and Results—

Stable patients (n=29; 27 male; age, 70±5 years) with asymptomatic abdominal aortic aneurysms (4.0 to 6.6 cm) were recruited from a surveillance program and imaged using a 3-T MRI scanner before and 24 to 36 hours after administration of ultrasmall superparamagnetic particles of iron oxide (USPIO). The change in T2* value on T2*-weighted imaging was used to detect accumulation of USPIO within the abdominal aortic aneurysm. Histological examination of aneurysm tissue confirmed colocalization and uptake of USPIO in areas with macrophage infiltration. Patients with distinct mural uptake of USPIO had a 3-fold higher growth rate (n=11, 0.66 cm/y;
P
=0.020) than those with no (n=6, 0.22 cm/y) or nonspecific USPIO uptake (n=8, 0.24 cm/y) despite having similar aneurysm diameters (5.4±0.6, 5.1±0.5, and 5.0±0.5 cm, respectively;
P
>0.05). In 1 patient with an inflammatory aneurysm, there was a strong and widespread uptake of USPIO extending beyond the aortic wall.

Conclusions—
Uptake of USPIO in abdominal aortic aneurysms identifies cellular inflammation and appears to distinguish those patients with more rapidly progressive abdominal aortic aneurysm expansion. This technique holds major promise as a new method of risk-stratifying patients with abdominal aortic aneurysms that extends beyond the simple anatomic measure of aneurysm diameter.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00794092.
Mortality Implications of Primary Percutaneous Coronary Intervention Treatment Delays: Insights From the Assessment of Pexelizumab in Acute Myocardial Infarction Trial
Authors: Hudson Michael P. , Armstrong Paul W. , O'Neil William W. , Stebbins Amanda L. , Weaver W. Douglas , Widimsky Petr , Aylward Philip E. , Ruzyllo Witold , Holmes David , Mahaffey Kenneth W. , Granger Christopher B. 
Published: February 2011

Background—
Prior studies demonstrate a direct relationship between treatment delays to primary percutaneous intervention and mortality in patients with ST-segment elevation myocardial infarction (STEMI). This analysis compared the relationship of symptom onset-to-balloon time and door-to-balloon time on mortality in patients with STEMI.

Methods and Results—

We analyzed different treatment delays (symptom onset-to-balloon time, door-to-balloon time) and mortality in 5745 STEMI patients. Baseline characteristics, flow grade, 90-day mortality, and clinical outcomes were compared in patients stratified by treatment delay. Multivariable logistic regression modeling was performed to assess the independent and relative effect of each treatment delay on 90-day mortality. Female sex, increased age, and worse thrombolysis in myocardial infarction flow grade were significantly associated with longer symptom onset-to-balloon times and door-to-balloon times. Longer symptom onset-to-balloon time was significantly associated with worse 90-day mortality (3.7%, 4.2%, and 6.5% for time delays <3 hours, 3 to 5 hours, and >5 hours, respectively,
P
<0.0001). Similarly, longer door-to-balloon times were significantly associated with worse 90-day mortality (3.2%, 4.0%, 4.6%, and 5.3% for delays <60 minutes, 60 to 90 minutes, 90 to 120 minutes, and ≥120 minutes respectively,
P
<0.0001). In a multivariate model of 90-day mortality, door-to-balloon time (χ
2
6.0,
P
<0.014), and symptom onset-to-hospital arrival (χ
2
9.8,
P
<0.007) remained independent determinants.

Conclusions—
Both symptom onset-to-balloon time and hospital door-to-balloon time are strongly associated with 90-day mortality following STEMI.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00091637.