bluuebunny/crossref_metadata_2025_split huggingface dataset:
OPERATIONS PRESERVING GLOBAL RIGIDITY OF GENERIC DIRECTION-LENGTH FRAMEWORKS
Authors: JACKSON BILL , JORDÁN TIBOR 
Published: January 2011

A two-dimensional direction-length framework is a pair (G, p), where G = (V; D, L) is a graph whose edges are labeled as 'direction' or 'length' edges, and a map p from V to ℝ2. The label of an edge uv represents a direction or length constraint between p(u) and p(v). The framework (G, p) is called globally rigid if every other framework (G, q) in which the direction or length between the endvertices of corresponding edges is the same, is 'congruent' to (G, p), i.e. it can be obtained from (G, p) by a translation and, possibly, a dilation by -1. We show that labeled versions of the two Henneberg operations (0-extension and 1-extension) preserve global rigidity of generic direction-length frameworks. These results, together with appropriate inductive constructions, can be used to verify global rigidity of special families of generic direction-length frameworks.
Impact of high-level transformations within the ROCCC framework
Authors: Buyukkurt Betul , Cortes John , Villarreal Jason , Najjar Walid A. 
Published: January 2011

Reconfigurable computers, where one or more FPGAs are attached to a conventional microprocessor, are promising platforms for code acceleration. Despite their advantages, programmability concerns and the lack of efficient design tools/compilers for FPGAs are preventing the technology's widespread adoption. The traditional compiler technology is microprocessor-based-systems-specific and needs to be customized and augmented to address the needs in reconfigurable computing. The challenges are several due to the resources and performance constraints for FPGAs being drastically different than those of microprocessors, and also that compiling for FPGAs requires laying the computation in space by a circuit rather than in time by a sequence of instructions.
ROCCC is an optimizing C-to-VHDL compiler specifically targeting the reconfigurable computer platforms. ROCCC includes several high-level optimizations that parallelize and optimize the source code for minimized area and critical path length and maximized throughput. This article presents the effect of ROCCC's high-level transformations on the performance of the generated VHDL output. ROCCC utilizes: (1) several array access optimizations to eliminate redundant memory accesses, (2) procedure-level optimizations to achieve circuit area reductions of up to 88% compared to circuit areas generated from unoptimized codes, (3) loop-level optimizations to increase the throughput, and (4) transformations unique to certain classes of applications. The preceding listed features help ROCCC generate circuits with very large degrees of parallelism capable of very high computation rates.
Estrogen and Cytochrome P450 1B1 Contribute to Both Early- and Late-Stage Head and Neck Carcinogenesis
Authors: Shatalova Ekaterina G. , Klein-Szanto Andres J.P. , Devarajan Karthik , Cukierman Edna , Clapper Margie L. 
Published: January 2011

AbstractSquamous cell carcinoma of the head and neck (HNSCC) is the sixth most common type of cancer in the United States. The goal of this study was to evaluate the contribution of estrogens to the development of HNSCCs. Various cell lines derived from early- and late-stage head and neck lesions were used to characterize the expression of estrogen synthesis and metabolism genes, including cytochrome P450 (CYP) 1B1, examine the effect of estrogen on gene expression, and evaluate the role of CYP1B1 and/or estrogen in cell motility, proliferation, and apoptosis. Estrogen metabolism genes (CYP1B1, CYP1A1, catechol-o-methyltransferase, UDP-glucuronosyltransferase 1A1, and glutathione-S-transferase P1) and estrogen receptor (ER) β were expressed in cell lines derived from both premalignant (MSK-Leuk1) and malignant (HNSCC) lesions. Exposure to estrogen induced CYP1B1 2.3- to 3.6-fold relative to vehicle-treated controls (P = 0.0004) in MSK-Leuk1 cells but not in HNSCC cells. CYP1B1 knockdown by shRNA reduced the migration and proliferation of MSK-Leuk1 cells by 57% and 45%, respectively. Exposure of MSK-Leuk1 cells to estrogen inhibited apoptosis by 26%, whereas supplementation with the antiestrogen fulvestrant restored estrogen-dependent apoptosis. Representation of the estrogen pathway in human head and neck tissues from 128 patients was examined using tissue microarrays. The majority of the samples exhibited immunohistochemical staining for ERβ (91.9%), CYP1B1 (99.4%), and 17β-estradiol (88.4%). CYP1B1 and ERβ were elevated in HNSCCs relative to normal epithelium (P = 0.024 and 0.008, respectively). These data provide novel insight into the mechanisms underlying head and neck carcinogenesis and facilitate the identification of new targets for chemopreventive intervention. Cancer Prev Res; 4(1); 107–15. ©2011 AACR.
Naftopidil, a Selective α1-Adrenoceptor Antagonist, Suppresses Human Prostate Tumor Growth by Altering Interactions between Tumor Cells and Stroma
Authors: Hori Yasuhide , Ishii Kenichiro , Kanda Hideki , Iwamoto Yoichi , Nishikawa Kohei , Soga Norihito , Kise Hideaki , Arima Kiminobu , Sugimura Yoshiki 
Published: January 2011

Abstract
In prostate cancer, tumor–stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha1-adrenoceptor (α1-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G1 cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective α1-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and α1-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G1 cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells. Cancer Prev Res; 4(1); 87–96. ©2011 AACR.
The Role of NAG-1/GDF15 in the Inhibition of Intestinal Polyps in APC/Min Mice by Sulindac
Authors: Wang Xingya , Kingsley Philip J. , Marnett Larry J. , Eling Thomas E. 
Published: January 2011

Abstract
The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon carcinogenesis by NSAIDs, we evaluated several sulindac derivatives [des-methyl (DM)-sulindac sulfide and its prodrug DM-sulindac] that do not inhibit COX-2 activity. Sulindac sulfide and DM-sulindac induced the expression of NAG-1/GDF15 in HCT116 cells as determined by quantitative real-time PCR and Western blot. We fed APC/Min mice with 320 ppm of sulindac and doses of DM-sulindac. Only sulindac significantly inhibited tumor formation inAPC/Min mice. To determine the pharmacokinetic properties of sulindac and DM-sulindac in vivo, wild-type C57/B6 mice were fed with sulindac and DM-sulindac at 80, 160, and 320 ppm. High-performance liquid chromatography analysis revealed that the conversion of DM-sulindac to DM-sulindac sulfide (active form) was less efficient than the conversion of sulindac to sulindac sulfide (active form) in the mice. Lower levels of DM-sulindac sulfide accumulated in intestinal and colon tissues in comparison with sulindac sulfide. In addition, NAG-1/GDF15 was induced in the liver of sulindac-fed mice but not in the DM-sulindac–fed mice. Collectively, our results suggest that the tumor-inhibitory effects of sulindac in APC/Min mice may be due to, in part, NAG-1/GDF15 induction in the liver. Our study also suggests that pharmacologic properties should be carefully evaluated when developing drug candidates. Cancer Prev Res; 4(1); 150–60. ©2011 AACR.
The Search for Unaffected Individuals with Lynch Syndrome: Do the Ends Justify the Means?
Authors: Hampel Heather , de la Chapelle Albert 
Published: January 2011

Abstract
Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers yet it is underrecognized in clinical practice. The relative merits of screening for Lynch syndrome among healthy adults without cancer versus among adults with colorectal or endometrial cancer are discussed in this Perspective article. Newly diagnosed colorectal cancer patients are a much easier target population for screening and this approach leads to more informative genetic test results, at a lower cost in most cases. Cancer Prev Res; 4(1); 1–5. ©2011 AACR.
The Prostaglandin Transporter Regulates Adipogenesis and Aromatase Transcription
Authors: Subbaramaiah Kotha , Hudis Clifford A. , Dannenberg Andrew J. 
Published: January 2011

Abstract
Cytochrome P450 aromatase, encoded by the CYP19 gene, catalyzes estrogen synthesis. In obese postmenopausal women, increased estrogen synthesis in adipose tissue has been linked to hormone-dependent breast carcinogenesis. Hence, it is important to elucidate the mechanisms that regulate CYP19 gene expression. Prostaglandin E2 (PGE2) stimulates the cyclic AMP (cAMP) → protein kinase A (PKA) → cAMP responsive element binding protein (CREB) pathway leading to increased CYP19 transcription. The prostaglandin transporter (PGT) removes PGE2 from the extracellular milieu and delivers it to the cytosol, where it is inactivated. The main objective of this study was to determine whether PGT regulates CYP19 transcription. Silencing of PGT in preadipocytes increased PGE2 levels in the extracellular medium, thereby stimulating the cAMP → PKA pathway resulting in enhanced interaction between pCREB, p300, and the CYP19 I.3/II promoter. A reciprocal decrease in the interaction between the CYP19 I.3/II promoter and BRCA1, a repressor of CYP19 transcription, was observed. Overexpressing PGT reduced extracellular PGE2 levels, suppressed the cAMP → PKA pathway, enhanced the interaction between BRCA1 and p300, and inhibited aromatase expression. We also compared the PGT → aromatase axis in preadipocytes versus adipocytes. Aromatase levels were markedly increased in preadipocytes versus adipocytes. This increase in aromatase was explained, at least in part, by reduced PGT levels leading to enhanced PGE2 → cAMP → PKA signaling. In addition to regulating aromatase expression, PGT-mediated changes in extracellular PGE2 levels were a determinant of adipocyte differentiation. Collectively, these results suggest that PGT modulates adipogenesis and thereby PGE2-mediated activation of the cAMP → PKA → CREB pathway leading to altered CYP19 transcription and aromatase activity. Cancer Prev Res; 4(2); 194–206. ©2011 AACR.
Neural Crest–Derived Stem Cells Migrate and Differentiate Into Cardiomyocytes After Myocardial Infarction
Authors: Tamura Yuichi , Matsumura Keisuke , Sano Motoaki , Tabata Hidenori , Kimura Kensuke , Ieda Masaki , Arai Takahide , Ohno Yohei , Kanazawa Hideaki , Yuasa Shinsuke , Kaneda Ruri , Makino Shinji , Nakajima Kazunori , Okano Hideyuki , Fukuda Keiichi 
Published: January 2011

Objective—
We recently demonstrated that primitive neural crest–derived (NC) cells migrate from the cardiac neural crest during embryonic development and remain in the heart as dormant stem cells, with the capacity to differentiate into various cell types, including cardiomyocytes. Here, we examined the migration and differentiation potential of these cells on myocardial infarction (MI).

Methods and Results—
We obtained double-transgenic mice by crossing protein-0 promoter-Cre mice with Floxed–enhanced green fluorescent protein mice, in which the NC cells express enhanced green fluorescent protein. In the neonatal heart, NC stem cells (NCSCs) were localized predominantly in the outflow tract, but they were also distributed in a gradient from base to apex throughout the ventricular myocardium. Time-lapse video analysis revealed that the NCSCs were migratory. Some NCSCs persisted in the adult heart. On MI, NCSCs accumulated at the ischemic border zone area (BZA), which expresses monocyte chemoattractant protein-1 (MCP-1). Ex vivo cell migration assays demonstrated that MCP-1 induced NCSC migration and that this chemotactic effect was significantly depressed by an anti-MCP-1 antibody. Small NC cardiomyocytes first appeared in the BZA 2 weeks post-MI and gradually increased in number thereafter.

Conclusion—
These results suggested that NCSCs migrate into the BZA via MCP-1/CCR2 signaling and contribute to the provision of cardiomyocytes for cardiac regeneration after MI.
Association of Adiponectin, Resistin, and Vascular Inflammation
Authors: Choi Hae Yoon , Kim Sungeun , Yang Sae Jeong , Yoo Hye Jin , Seo Ji A. , Kim Sin Gon , Kim Nan Hee , Baik Sei Hyun , Choi Dong Seop , Choi Kyung Mook 
Published: January 2011

Objective—

Adiponectin and resistin are adipokines that are linked to obesity, inflammation, and atherosclerosis.
18
F-Fluorodeoxyglucose (FDG) positron emission tomography is a promising imaging technique that can be used to evaluate vascular inflammation.

Methods and Results—

We measured adiponectin and resistin levels, as well as traditional cardiovascular risk factors, in 60 obese subjects and 60 nonobese controls. In addition, we compared carotid intima-media thickness and target-to-background ratio (TBR) measured using
18
F-fluorodeoxyglucose–positron emission tomography/computed tomography. The mean TBR values were significantly higher in the obese group compared with normal subjects, although their mean carotid intima-media thickness levels were not significantly different. Serum adiponectin levels showed a significant negative correlation with mean TBR values (
r
=−0.215,
P
=0.020), whereas resistin levels were positively correlated with mean TBR values (
r
=0.214,
P
=0.021). Multiple linear regression analysis showed that mean TBR values were independently associated with body mass index, high-sensitivity C-reactive protein, and resistin levels (
R
2
=0.308).

Conclusion—
Adiponectin and resistin may be useful as biomarkers to reflect vascular inflammation. In particular, resistin levels were independently associated with vascular inflammation even after adjusting for other cardiovascular risk factors.
Long-Term Outcome and Impact of Surgery on Adults With Coronary Arteries Originating From the Opposite Coronary Cusp
Authors: Krasuski Richard A. , Magyar Dari , Hart Stephen , Kalahasti Vidyasagar , Lorber Richard , Hobbs Robert , Pettersson Gosta , Blackstone Eugene 
Published: January 2011

Background—
An anomalous coronary artery from the opposite sinus of Valsalva may increase sudden death risk in children and young adults, and surgical intervention is often recommended. The impact of this lesion when recognized in the adult and its management are ill defined.

Methods and Results—

We reviewed 210 700 cardiac catheterizations performed over a 35-year period at a single institution and identified 301 adults with an anomalous coronary artery from the opposite sinus of Valsalva, either anomalous right coronary artery from the left cusp or anomalous left main coronary artery from the right cusp. Patients were stratified by the pathway of the anomalous artery and the chosen treatment. Among the 301 patients with anomalous coronary artery from the opposite sinus of Valsalva (0.14% of the cohort), 79% had anomalous right coronary artery from the left cusp, and 18% had an interarterial course (IAC). Patients with IAC were younger (52±13 versus 59±13 years;
P
=0.001) and more likely to undergo surgical intervention (52% versus 27%;
P
<0.001), but mortality was not increased with IAC. Among the 54 patients with IAC, 28 underwent surgical repair with no perioperative deaths. Patients evaluated since 2000 were significantly more likely to be referred for surgery (
P
=0.004). Surgical patients were more likely to have abnormal stress tests (90% versus 43%;
P
=0.01) and had more extensive atherosclerosis but less diabetes mellitus (0% versus 23%;
P
=0.01). Long-term survival at 10 years appeared similar in both groups.

Conclusions—
In this single-center cohort study of patients with an anomalous coronary artery from the opposite sinus of Valsalva, surgical management appears to have been favored recently. Despite no perioperative mortality, a positive impact on long-term survival was not observed. The impact of surgery in older adults with anomalous coronary arteries arising from the opposite coronary sinus with IAC deserves further study.
Microvascular Function Predicts Cardiovascular Events in Primary Prevention
Authors: Anderson Todd J. , Charbonneau Francois , Title Lawrence M. , Buithieu Jean , Rose M. Sarah , Conradson Heather , Hildebrand Kathy , Fung Marinda , Verma Subodh , Lonn Eva M. 
Published: January 2011

Background—
Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men.

Methods and Results—

The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92;
P
=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90;
P
=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83;
P
=0.002) but not C-reactive protein (
P
=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (
P
<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (
P
=0.24).

Conclusions—
In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.
Mechanisms of Atrial Tachyarrhythmias Associated With Coronary Artery Occlusion in a Chronic Canine Model
Authors: Nishida Kunihiro , Qi Xiao Yan , Wakili Reza , Comtois Philippe , Chartier Denis , Harada Masahide , Iwasaki Yu-ki , Romeo Philippe , Maguy Ange , Dobrev Dobromir , Michael Georghia , Talajic Mario , Nattel Stanley 
Published: January 2011

Background—
Coronary artery disease predisposes to atrial fibrillation (AF), but the effects of chronic atrial ischemia/infarction on AF-related substrates are unknown.

Methods and Results—

Regional right atrial myocardial infarction (MI) was created in 40 dogs by ligating an artery that supplies the right atrial free wall and not the ventricles; 35 sham dogs with the same artery isolated but not ligated were controls. Dogs were observed 8 days after MI and subjected to open-chest study, in vitro optical mapping, and/or cell isolation for patch-clamp and Ca
2+
imaging on day 8. Holter ECGs showed more spontaneous atrial ectopy in MI dogs (eg, 662±281 on day 7 versus 34±25 ectopic complexes per day at baseline; 52±21 versus 1±1 atrial tachycardia episodes per day). Triggered activity was increased in MI border zone cells, which had faster decay of caffeine-evoked Ca
2+
transients and enhanced (by ≈73%) Na
+
-Ca
2+
exchange current. Spontaneous Ca
2+
sparks (confocal microscopy) occurred under β-adrenergic stimulation in more MI dog cells (66±9%) than in control cells (29±4%;
P
<0.01). Burst pacing induced long-lasting AF in MI dogs (1146±259 versus 30±14 seconds in shams). Increased border zone conduction heterogeneity was confirmed by both bipolar electrode mapping in vivo and optical mapping. Optical mapping demonstrated stable border zone reentry in all 9 MI preparations but in none of 6 shams. Border zone tissue showed increased fibrous tissue content.

Conclusions—

Chronic atrial ischemia/infarction creates substrates for both spontaneous ectopy (Ca
2+
-release events, increased Na
+
-Ca
2+
exchange current) and sustained reentry (conduction abnormalities that anchor reentry). Thus, chronic atrial infarction in dogs promotes both AF triggers and the substrate for AF maintenance. These results provide novel insights into potential AF mechanisms in patients with coronary artery disease.
Quantifying Differences between 2-m Temperature Observations and Reanalysis Pressure-Level Temperatures in Northwestern North America
Authors: Reuten Christian , Moore R. Dan , Clarke Garry K. C. 
Published: January 2011

AbstractIn northwestern North America, which is a large area with complex physiography, Climatic Research Unit (CRU) Time Series, version 2.1, (TS 2.1) gridded monthly mean 2-m temperatures are systematically lower than interpolated monthly averaged North American Regional Reanalysis (NARR) pressure-level temperatures––in particular, in the winter. Quantification of these differences based on CRU gridded observations can be used to estimate pressure-level temperatures from CRU 2-m temperatures (1901–2002) that predate the NARR period (since 1979). Such twentieth-century pressure-level temperature fields can be used in glacier mass-balance modeling and as an alternative to calibrating general circulation model control runs, avoiding the need for accurate boundary layer parameterization. In this paper, an approach is presented that is transferable to moisture, wind, and other 3D fields with potential applications in wind power generation, ecology, and air quality. At each CRU grid point, the difference between CRU and NARR is regressed against seven predictors in CRU (mean temperature, daily temperature range, precipitation, vapor pressure, cloud cover, and number of wet and frost days) for the period of overlap between CRU and NARR (1979–2002). Bayesian model averaging (BMA) is used to avoid overfitting the CRU–NARR differences and underestimating uncertainties. In cross validations, BMA provides reliable posterior predictions of the CRU–NARR differences and outperforms predictions from three alternative models: the constant model (24-yr mean), the regression model of highest Bayesian model probability, and the full model retaining all seven predictors in CRU.