bluuebunny/crossref_metadata_2025 huggingface dataset:
GENERATING BALANCED LEARNING AND TEST SETS FOR FUNCTION APPROXIMATION PROBLEMS
Authors: FLORIDO J. P. , POMARES H. , ROJAS I.
Published: June 2011

In function approximation problems, one of the most common ways to evaluate a learning algorithm consists in partitioning the original data set (input/output data) into two sets: learning, used for building models, and test, applied for genuine out-of-sample evaluation. When the partition into learning and test sets does not take into account the variability and geometry of the original data, it might lead to non-balanced and unrepresentative learning and test sets and, thus, to wrong conclusions in the accuracy of the learning algorithm. How the partitioning is made is therefore a key issue and becomes more important when the data set is small due to the need of reducing the pessimistic effects caused by the removal of instances from the original data set. Thus, in this work, we propose a deterministic data mining approach for a distribution of a data set (input/output data) into two representative and balanced sets of roughly equal size taking the variability of the data set into consideration with the purpose of allowing both a fair evaluation of learning's accuracy and to make reproducible machine learning experiments usually based on random distributions. The sets are generated using a combination of a clustering procedure, especially suited for function approximation problems, and a distribution algorithm which distributes the data set into two sets within each cluster based on a nearest-neighbor approach. In the experiments section, the performance of the proposed methodology is reported in a variety of situations through an ANOVA-based statistical study of the results.
APPLICATION OF RECURRENCE QUANTIFICATION ANALYSIS FOR THE AUTOMATED IDENTIFICATION OF EPILEPTIC EEG SIGNALS
Authors: ACHARYA U. RAJENDRA , SREE S. VINITHA , CHATTOPADHYAY SUBHAGATA , YU WENWEI , ANG PENG CHUAN ALVIN
Published: June 2011

Epilepsy is a common neurological disorder that is characterized by the recurrence of seizures. Electroencephalogram (EEG) signals are widely used to diagnose seizures. Because of the non-linear and dynamic nature of the EEG signals, it is difficult to effectively decipher the subtle changes in these signals by visual inspection and by using linear techniques. Therefore, non-linear methods are being researched to analyze the EEG signals. In this work, we use the recorded EEG signals in Recurrence Plots (RP), and extract Recurrence Quantification Analysis (RQA) parameters from the RP in order to classify the EEG signals into normal, ictal, and interictal classes. Recurrence Plot (RP) is a graph that shows all the times at which a state of the dynamical system recurs. Studies have reported significantly different RQA parameters for the three classes. However, more studies are needed to develop classifiers that use these promising features and present good classification accuracy in differentiating the three types of EEG segments. Therefore, in this work, we have used ten RQA parameters to quantify the important features in the EEG signals.These features were fed to seven different classifiers: Support vector machine (SVM), Gaussian Mixture Model (GMM), Fuzzy Sugeno Classifier, K-Nearest Neighbor (KNN), Naive Bayes Classifier (NBC), Decision Tree (DT), and Radial Basis Probabilistic Neural Network (RBPNN). Our results show that the SVM classifier was able to identify the EEG class with an average efficiency of 95.6%, sensitivity and specificity of 98.9% and 97.8%, respectively.
TIME-AWARE AND WEIGHTED FAULT SEVERITY BASED METRICS FOR TEST CASE PRIORITIZATION
Authors: MARY S. A. SAHAAYA ARUL , KRISHNAMOORTHI R.
Published: June 2011

Test metrics succeed in analyzing the current level of maturity in testing and give a projection on the way to proceed with testing activities by allowing us to set goals and predict future trends. The objective of test metrics is to capture the planned and actual quantities: the effort, time and resources required to complete all the phases of development of the software project. Test case prioritization is an effective and practical technique in regression testing. It schedules test cases in order of precedence that increases their ability to meet some performance goals, such as code coverage, rate of fault detection. In this paper, we present a new metrics, based on varying requirement priorities, test case priorities, test case execution time, and fault severities. The case study illustrates that the rate of "units-of-test-case-priority-satisfied- per-unit-test-case-time" can be increased, and with improvement on testing quality and customer satisfaction. To assess the practicality of our approach, we apply it to a realistic example from the industrial projects. Also we summarize a test process measurement project of TECHZONE™ (Software development Concern with Testing Department) test teams, and analyze the effectiveness of set of metrics for cost, time, and quality to measure the quality of test process based on the results of the proposed metrics.
EXPLOITING INTELLIGENT CONTENT VIA AXMEDIS/MPEG-21 FOR MODELLING AND DISTRIBUTING NEWS
Authors: BELLINI PIERFRANCESCO , BRUNO IVAN , NESI PAOLO
Published: June 2011

The content technology needs to attain forms with more intelligence, flexibility and complete features than those being currently on the market or proposed by standards. In this paper, an analysis of the state of the art about intelligent and complex content models is presented. The analysis allowed identifying a number of topics and features which models and formats should evolve according to. The work has been used to extend AXMEDIS content model and format which in turn is grounded on MPEG-21, SMIL, HTML, and other standards. The Extended AXMEDIS format presents a set of new features among them: semantic descriptors, extended annotations, intelligent behavioral and semantic computing capabilities. The newly obtained format has been compared against NewsML which is one of the most widespread formats for news production and distribution. The management of news has some peculiarities such as container, production tools and players, that may take advantage of the intelligent content features and applications. Moreover, news have to be massively processed for ingestion and repurposing, and present relevant requirements on right control. Also these features may be satisfied by AXMEDIS tools. To this end, a comparative analysis of processing and modeling NewsML with AXMEDIS tools and format has been performed and reported to verify the usage. In addition, AXMEDIS format can be profitably used for a range of innovative applications of intelligent content.
SEMANTIC DESCRIPTION OF WEB 3D WORLDS THROUGH SOCIAL TAGGING
Authors: PITTARELLO FABIO
Published: June 2011

Free-tagging is one of the leading mechanisms characterizing the so-called web 2.0, enabling users to define collaboratively the meaning of web data for improving their findability. Tagging is applied in several forms to hypermedia data, that represent the largest part of the information on the web.

In spite of that, there is a growing part of web data made of 3D vectors representing real objects such as trees, houses and people that lacks any semantic definition. Such situation prevents any advanced use of the data contained inside these 3D worlds, including seeking, filtering and manipulation of the objects represented by vectors.

This work proposes a bottom-up approach for adding semantics to such data, based on the collaborative effort of users navigating the web. This paper, after describing the similarities and the differences that characterize tagging for hypermedia and interactive 3D worlds, discusses the design choices that have guided the definition of a specification for associating tags to 3D objects.

The proposed specification is based on X3D — the ISO standard for describing 3D interactive worlds for the net — and permits to tag a large part of the existing 3D worlds compliant with this standard.

A client-software web architecture for tagging and navigating 3D worlds compliant with the specification presented is illustrated. Finally, a web-based user interface for tagging and browsing the result of the cooperative activity of users is presented and applied to a complex 3D world related to the cultural heritage domain.
REQUIREMENT RISK LEVEL FORECAST USING BAYESIAN NETWORKS CLASSIFIERS
Authors: DEL ÁGUILA ISABEL MARÍA , DEL SAGRADO JOSÉ
Published: June 2011

Requirement engineering is a key issue in the development of a software project. Like any other development activity it is not without risks. This work is about the empirical study of risks of requirements by applying machine learning techniques, specifically Bayesian networks classifiers. We have defined several models to predict the risk level for a given requirement using three dataset that collect metrics taken from the requirement specifications of different projects. The classification accuracy of the Bayesian models obtained is evaluated and compared using several classification performance measures. The results of the experiments show that the Bayesians networks allow obtaining valid predictors. Specifically, a tree augmented network structure shows a competitive experimental performance in all datasets. Besides, the relations established between the variables collected to determine the level of risk in a requirement, match with those set by requirement engineers. We show that Bayesian networks are valid tools for the automation of risks assessment in requirement engineering.
RISK ASSESSMENT IN MULTI-DISCIPLINARY (SOFTWARE+) ENGINEERING PROJECTS
Authors: BIFFL STEFAN , MOSER THOMAS , WINKLER DIETMAR
Published: June 2011

Software systems in safety-critical industrial automation systems, such as power plants and steel mills, become increasingly large, complex, and distributed. For assessing risks, like low product quality and project cost and duration overruns, to trustworthy services provided by software as part of automation systems there are established risk analysis approaches based on data collection from project participants and data models. However, in multi-disciplinary engineering projects there are often semantic gaps between the software tools and data models of the participating engineering disciplines, e.g., mechanic, electrical, and software engineering.

In this paper we discuss current limitations to risk assessment in (software+) engineering projects and introduce the SEMRISK approach for risk assessment in projects with semantically heterogeneous software tools and data models. The SEMRISK approach provides the knowledge engineering foundation to allow an end-to-end view for service-relevant data elements such as signals, by providing a project domain ontology and mappings to the tool data models of the involved engineering disciplines.

We empirically evaluate the effectiveness and efficiency of the approach based on a real-world industrial use case from the safety-critical power plant domain. Major results are that the approach was effective and considerably more efficient than the current approach at the industry partner.
UNDERSTANDING THE ANTECEDENTS TO AN ENTREPRENEURIAL FIRM'S INTENT TO ENGAGE IN INTERNATIONAL STRATEGIC ALLIANCES
Authors: GEH EUGENE Z.
Published: June 2011

The article has been retracted.
Trail-Laying Behaviour as a Function of Resource Quality in the AntCamponotus rufipes
Authors: Schilman Pablo E.
Published: June 2011

Chemical trails have been shown to act as an orientation cue in some ant species. Here, I report that the trail-laying behaviour in the nectar-feeding ant,Camponotus rufipes, varies with the concentration of the sucrose solutions collected. Single workers collected solutions of different sucrose concentrations (5%, 20%, and 40% in weight) during 4 consecutive visits to the resource, and their trail-marking behaviour was recorded on soot-coated slides during their first and last visits. Results suggest that these chemical trails provide both an orientation cue between the nest and the food source, as previously suggested forCamponotusants, as well as information about food quality.
Serum Positive for the Autoantibody against theβ1-Adrenoceptor from Chinese Patients with Congestive Heart Failure DecreasesIssin Mouse Cardiac Myocytes
Authors: Wang Yuan-yuan , Ma Zhi-Yong , Li Xiao-Dong , Wang Jian-chun , Zhang Wei , Li Li , Zhang Yun
Published: June 2011

Autoantibodies targeting the β1-adrenergic receptor (AAB-β1) display agonist-like effects, which may have a pathogenic role in the progression of heart failure. Here, we used the electrophysiological recordings to explore the effects of AAB-β1-positive serum from Chinese patients with heart failure on the activity of the peak transient outward potassium current (Ito) and the end 50 ms steady-state potassium current (Iss) in mouse cardiac myocytes. We found that the AAB-β1-positive serum had no effect on the activity ofIto, but it produced a decrease in the currents ofIss. A low concentration of positive serum (1/100) had a small inhibitory effect onIss. However, positive serum at 1 : 10, 1 : 20, and 1 : 50 significantly decreasedIss. The concentration-dependence analysis showed that the EC50of AAB-β1-positive serum was 1/60.24 and its nH was 2.86. It indicated that the AAB-β1could inhibitIssin mouse cardiomyocyte in a concentration-dependent manner.
Blood-Brain Barrier Dysfunction in Epileptogenesis of the Temporal Lobe
Authors: Weissberg Itai , Reichert Aljoscha , Heinemann Uwe , Friedman Alon
Published: June 2011

Epilepsy of the temporal lobe (TLE) is the most common form of focal epilepsy, and in adults, it most frequently develops after injury. However, the mechanisms by which a normal functioning brain turns into an epileptic one still remain obscure. Recent studies point to vascular involvement and particularly blood-brain barrier (BBB) dysfunction in the development of epilepsy. The BBB is a specialized structure which functions to control the neuronal extracellular milieu. BBB dysfunction is found in many diseases of the central nervous system, including stroke, traumatic injuries, tumors and infections. Interestingly, all these insults may initiate an epileptogenic process which eventually leads to spontaneous, recurrent seizures. This epileptogenic time frame usually lasts weeks, months, or even years in man, and days to weeks in rodents and may serve as a “window of opportunity” for the prevention of epilepsy. However, no prevention strategy exists, stressing the importance of research into the mechanisms of epileptogenesis. Here, we will underscore recent experiments suggesting that BBB dysfunction directly induces epileptogenesis. We will provide new evidence to support the hypothesis that BBB breakdown and specifically exposure of temporal lobe structures to the most common serum protein, albumin, is sufficient to induce epileptogenesis.
Harmonic Numbers and Cubed Binomial Coefficients
Authors: Sofo Anthony
Published: June 2011

Euler related results on the sum of the ratio of harmonic numbers
and cubed binomial coefficients are investigated in this paper. Integral
and closed-form representation of sums are developed in terms of zeta and
polygamma functions. The given representations are new.
Enhancing Heat Transfer of Drag-Reducing Surfactant Solution by an HEV Static Mixer with Low Pressure Drop
Authors: Shi Haifeng , Wang Yi , Ge Wu , Fang Bo , Huggins Jacob T. , Huber Thaddaus R. , Zakin Jacques L.
Published: June 2011

A novel high-efficiency vortex (HEV) static mixer was used to locally enhance the heat transfer coefficient of a drag-reducing fluid, Ethoquad O/12 (EO12) (3 mM) with sodium salicylate (NaSal) (5 mM). Significant enhancement of heat transfer coefficients was observed. The Nusselt numbers were three to five times those of normal drag-reducing flow without mixer and were close to those of water at high Reynolds number with only modest energy penalty. In contrast, a Helix static mixer increased Nusselt number slightly with very high pressure loss. A performance number was used for comparisons among the HEV static mixer, the Helix static mixer, and water without mixer. The HEV static mixer had a performance number comparable to that of water. The enhanced heat transfer by the HEV static mixer resulted from streamwise vortices generated by the inclined tabs, which increased the convective heat transfer in the radial direction.
Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban
Authors: Zhou Qianxing , Bea Florian , Preusch Michael , Wang Hongjie , Isermann Berend , Shahzad Khurrum , Katus Hugo A. , Blessing Erwin
Published: June 2011

Aim. Thrombin not only plays a central role in thrombus formation and platelet activation, but also in induction of inflammatory processes. Activated factor X (FXa) is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. We assessed the hypothesis that rivaroxaban, a direct FXa inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions in anin vivomodel.Methods and Results. Rivaroxaban (1 or 5 mg/kg body weight/day) or standard chow diet was administered for 26 weeks to apolipoprotein E-deficient mice (n=20per group) with already established atherosclerotic lesions. There was a nonsignificant reduction of lesion progression in the high-concentration group, compared to control mice. FXa inhibition with 5 mg Rivaroxaban/kg/day resulted in increased thickness of the protective fibrous caps (12.3±3.8 μm versus10.1±2.7 μm;P<.05), as well as in fewer medial erosions and fewer lateral xanthomas, indicating plaque stabilizing properties. Real time-PCR from thoracic aortas revealed that rivaroxaban (5 mg/kg/day) treatment reduced mRNA expression of inflammatory mediators, such of IL-6, TNF-α, MCP-1, and Egr-1 (P<.05).Conclusions. Chronic administration of rivaroxaban does not affect lesion progression but downregulates expression of inflammatory mediators and promotes lesion stability in apolipoprotein E-deficient mice.
Making Space for Permanent Molars in Growing Baboon (Papio anubis) and Great Ape (Pan paniscusandP. troglodytes) Mandibles: Possible Ontogenetic Strategies and Solutions
Authors: Boughner Julia C.
Published: June 2011

While mandible proportions do not appear to constrain permanent molar initiation times, how adequate space is created in the corpus for these teeth in a timely way is not well understood. This question is important for explaining how primate tooth and jaw development and evolution are coordinated. Landmark and linear measurement data were used to characterize mandible shape, growth trajectory, and growth rate between two genera,PapioandPan, with contrasting permanent molar initiation schedules and mandible proportions. 3D geometric morphometric and 2D bivariate analyses showed genus-level differences in mandible morphology from birth that were amplified by different postnatal growth trajectories. Different corpus proportions and regional variation in corpus growth rates helped create space in a timely way for the molars. Regional corpus growth rates may evolve alongside permanent molar morphology and developmental timing to modify space available in the corpus for these teeth.
Single-Lung Transplantation in the Setting of Aborted Bilateral Lung Transplantation
Authors: Puri Varun , Guthrie Tracey , Scavuzzo Masina , Kreisel Daniel , Krupnick Alexander S. , Patterson G. Alexander , Meyers Bryan F.
Published: June 2011

Background. The outcome of patients undergoing a single-lung transplant in the setting of an aborted bilateral lung transplant is unclear.Methods. A retrospective review of single lung transplants at an institutional program.Results. Of the 543 lung transplants performed over the last 10 years, 31 (5.7%) were single-lung transplants. Nineteen of 31 (61%) were planned single-lung transplants, while 12/31 (39%) were intraoperatively aborted, double lung transplants converted to single-lung transplants. The aborted and planned groups were similar in age, lung allocation score and NYHA status. The reasons for aborted double lung transplantation were cardiac/hemodynamic instability 4/12 (33%), difficult pneumonectomy 3/12 (25%), size mismatch 4/12(33%), and technical issues 1/12 (8%). The aborted group had higher CPB utilization (5/12 versus 1/19, ), similar ischemic times (260 versus 234 min) and similar incidence of grade 3 primary graft dysfunction (6/12 versus 3/19, ). ECMO was required for graft dysfunction in 2 patients in the aborted group. The one and two-year survival was 84% and 79% in the planned group and 62% and 52% in the aborted group, respectively.Conclusions. Patients undergoing single-lung transplantation in the setting of an aborted bilateral lung transplant may be at a higher risk of worse outcomes.
Ovipositor Internal Microsculpture in the Relic SilverfishTricholepidion gertschi(Insecta: Zygentoma)
Authors: Matushkina Natalia A.
Published: June 2011

The microsculpture on the inside surface of the ovipositor of the relic silverfishTricholepidion gertschi(Wygodzinsky, 1961) (Insecta: Zygentoma) was studied with scanning electronic microscopy for the first time. Both the first and second valvulae ofT. gertschibear rather diverse sculptural elements: (1) microtrichia of various shapes and directed distally, (2) longitudinal ridges, (3) smooth regions, and (4) scattered dome-shaped sensilla. As in several other insects, the distally directed microtrichia most likely facilitate unidirectional movement of the egg during egg laying. Involvement of the ovipositor internal microsculpture also in the uptake of male genital products is tentatively suggested. From a phylogenetic point of view, the presence of internal microsculpture appears an ancestral peculiarity of the insect ovipositor.
Hyperplastic Polyps Are Innocuous Lesions in Hereditary Nonpolyposis Colorectal Cancers
Authors: Speake D. , O'Sullivan J. , Evans D. G. , Lalloo F. , Hill J. , McMahon R. F. T.
Published: June 2011

Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI) of sporadic, HNPCC, and familial hyperplastic polyps (HPs).Methods. Methylation-specific PCR (MSP) and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry) assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining.Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P=.186Chi2). The familial group demonstrated significantly less over all methylation levels (P=.004Chi2).Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting.
Forward Curvatures on Time Scales
Authors: Seyyidoglu M. S. , Tunçer Y. , Uçar D. , Berktaş M. K. , Hatipoğlu V. F.
Published: June 2011

We also introduce forward curvature of a curve and give some formulas to calculate forward curvature of a curve on time scales which may be an arbitrary closed subsets of the set of all real numbers. We also introduce the length of a curve parametrized by a time scale parameter in ℝ3.
The Current Role of Lymph Node Dissection in the Management of Renal Cell Carcinoma
Authors: Jamal Joseph Edmund , Jarrett Thomas William
Published: June 2011

The role of lymph node dissection remains controversial in the surgical management of renal cell carcinoma. Incidental renal masses are being diagnosed at increasing rates due to the routine use of CT scans. Despite the increase in incidental diagnosis of renal masses, 20% to 30% of patients present with metastatic disease. Currently, surgeons do not routinely perform lymph node dissection unless there is gross evidence of lymphadenopathy, as patients without clinical evidence of lymphadenopathy rarely have positive nodes at the time of surgery. Patients with metastatic disease to the regional lymph nodes have a poor overall prognosis. However, some evidence supports a therapeutic benefit of lymphadenectomy in these patients. Further, the staging information gained from diagnosing lymph node involvement may allow for the use of new agents to treat metastatic disease and effect outcomes.
Overcoming Hypoxia-Induced Apoptotic Resistance through Combinatorial Inhibition of GSK-3β and CDK1
Authors: Mayes Patrick A. , Dolloff Nathan G. , Daniel Colin J. , Liu J. Judy , Hart Lori S. , Kuribayashi Kageaki , Allen Joshua E. , Jee David I.H. , Dorsey Jay F. , Liu Yingqiu Y. , Dicker David T. , Brown J. Martin , Furth Emma E. , Klein Peter S. , Sears Rosalie C. , El-Deiry Wafik S.
Published: June 2011

Tumor hypoxia is an inherent impediment to cancer treatment that is both clinically significant and problematic. In this study, we conducted a cell-based screen to identify small molecules that could reverse the apoptotic resistance of hypoxic cancer cells. Among the compounds, we identified were a structurally related group that sensitized hypoxic cancer cells to apoptosis by inhibiting the kinases GSK-3β and cyclin-dependent kinase (CDK) 1. Combinatorial inhibition of these proteins in hypoxic cancer cells and tumors increased levels of c-Myc and decreased expression of c-IAP2 and the central hypoxia response regulator hypoxia-inducible factor (HIF) 1α. In mice, these compounds augmented the hypoxic tumor cell death induced by cytotoxic chemotherapy, blocking angiogenesis and tumor growth. Taken together, our findings suggest that combinatorial inhibition of GSK-3β and CDK1 augment the apoptotic sensitivity of hypoxic tumors, and they offer preclinical validation of a novel and readily translatable strategy to improve cancer therapy. Cancer Res; 71(15); 5265–75. ©2011 AACR.
Effects of Aerobic Exercise on Premenopausal Sex Hormone Levels: Results of the WISER Study, a Randomized Clinical Trial in Healthy, Sedentary, Eumenorrheic Women
Authors: Smith Alma J. , Phipps William R. , Arikawa Andrea Y. , O'Dougherty Maureen , Kaufman Beth , Thomas William , Schmitz Kathryn H. , Kurzer Mindy S.
Published: June 2011

Background: It is hypothesized that exercise can lead to a decrease in breast cancer risk through several hormonal and nonhormonal mechanisms. The WISER (Women In Steady Exercise Research) study investigated the effects of aerobic exercise on premenopausal sex hormone levels.

Methods: Three hundred ninety-one sedentary, healthy, young eumenorrheic women were randomized either into an exercise intervention of 30 minutes of aerobic exercise 5 times a week for approximately 16 weeks (n = 212) or into a control group (n = 179). Serum levels of estradiol, estrone sulfate, testosterone, and sex hormone–binding globulin (SHBG), all in the midfollicular phase, and of progesterone, in the midluteal phase, were measured at baseline and at the end of the 16-week period.

Results: Compared with the controls (n = 153), exercisers (n = 166) experienced significant increases in aerobic fitness, lean body mass, and decreases in percent body fat. There were no significant changes in body weight and menstrual cycle length between or within groups. Progesterone decreased significantly in exercisers; however, this reduction was similar to that of the control group. No significant changes between or within groups were found for any of the other sex hormones or SHBG.

Conclusions: In premenopausal women, 16 weeks of 150 minutes per week of moderate aerobic exercise in young women did not significantly alter sex hormone or SHBG levels.

Impact: Any favorable effects that moderate aerobic exercise without an associated weight change may have on breast cancer risk in premenopausal women are unlikely to be a consequence of changes in levels of sex hormones or SHBG. Cancer Epidemiol Biomarkers Prev; 20(6); 1098–106. ©2011 AACR.
Inherited Variants in Mitochondrial Biogenesis Genes May Influence Epithelial Ovarian Cancer Risk
Authors: Permuth-Wey Jennifer , Chen Y. Ann , Tsai Ya-Yu , Chen Zhihua , Qu Xiaotao , Lancaster Johnathan M. , Stockwell Heather , Dagne Getachew , Iversen Edwin , Risch Harvey , Barnholtz-Sloan Jill , Cunningham Julie M. , Vierkant Robert A. , Fridley Brooke L. , Sutphen Rebecca , McLaughlin John , Narod Steven A. , Goode Ellen L. , Schildkraut Joellen M. , Fenstermacher David , Phelan Catherine M. , Sellers Thomas A.
Published: June 2011

Background: Mitochondria contribute to oxidative stress, a phenomenon implicated in ovarian carcinogenesis. We hypothesized that inherited variants in mitochondrial-related genes influence epithelial ovarian cancer (EOC) susceptibility.

Methods: Through a multicenter study of 1,815 Caucasian EOC cases and 1,900 controls, we investigated associations between EOC risk and 128 single nucleotide polymorphisms (SNPs) from 22 genes/regions within the mitochondrial genome (mtDNA) and 2,839 nuclear-encoded SNPs localized to 138 genes involved in mitochondrial biogenesis (BIO, n = 35), steroid hormone metabolism (HOR, n = 13), and oxidative phosphorylation (OXP, n = 90) pathways. Unconditional logistic regression was used to estimate OR and 95% CI between genotype and case status. Overall significance of each gene and pathway was evaluated by using Fisher's method to combine SNP-level evidence. At the SNP level, we investigated whether lifetime ovulation, hormone replacement therapy (HRT), and cigarette smoking were confounders or modifiers of associations.

Results: Interindividual variation involving BIO was most strongly associated with EOC risk (empirical P = 0.050), especially for NRF1, MTERF, PPARGC1A, ESRRA, and CAMK2D. Several SNP-level associations strengthened after adjustment for nongenetic factors, particularly for MTERF. Statistical interactions with cigarette smoking and HRT use were observed with MTERF and CAMK2D SNPs, respectively. Overall variation within mtDNA, HOR, and OXP was not statistically significant (empirical P > 0.10).

Conclusion: We provide novel evidence to suggest that variants in mitochondrial biogenesis genes may influence EOC susceptibility.

Impact: A deeper understanding of the complex mechanisms implicated in mitochondrial biogenesis and oxidative stress may aid in developing strategies to reduce morbidity and mortality from EOC. Cancer Epidemiol Biomarkers Prev; 20(6); 1131–45. ©2011 AACR.
Relationship between Epidermal Growth Factor Receptor Status, p16INK4A, and Outcome in Head and Neck Squamous Cell Carcinoma
Authors: Young Richard J. , Rischin Danny , Fisher Richard , McArthur Grant A. , Fox Stephen B. , Peters Lester J. , Corry June , Lim Annette , Waldeck Kelly , Solomon Benjamin
Published: June 2011

Background: Human papilloma virus (HPV) infection is a powerful prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). Increased epidermal growth factor receptor (EGFR) gene copy number and protein expression have been reported to be negative predictors of outcome. This study examined the relationship between HPV status, EGFR gene copy number, EGFR protein expression, and clinical outcome in HNSCC patients treated with chemoradiation.

Methods: HPV status was determined using p16INK4A immunohistochemistry (IHC), EGFR gene copy number was evaluated with FISH, and EGFR protein expression by IHC in 212 subjects.

Results: EGFR FISH was positive in 41 of 204 (20%) patients and was negatively correlated with failure-free survival (FFS; HR = 1.84, P = 0.027) and overall survival (OS; HR = 1.78, P = 0.082). For p16INK4A, 85 of 200 (42.5%) patients were found to be p16 positive, including 75 of 131 (57%) with oropharyngeal cancer. Patients with p16-positive oropharyngeal cancer had significantly improved FFS (HR = 0.28, P < 0.001) and OS (HR = 0.31, P = 0.002). Only 2 of 126 (1.6%) oropharyngeal cancer patients were found to be p16+/EGFR FISH+. EGFR IHC was positive in 81 of 93 (87%) of patients and was associated with poorer FFS (HR = 1.98, P = 0.35) and OS (HR = 2.52, P = 0.22).

Conclusions: Increased EGFR gene copy number is largely restricted to p16INK4A-negative oropharyngeal cancer. Although p16INK4A and EGFR FISH are both predictive of outcome in univariate analyses, only p16INK4A remains independently predictive.

Impact: Knowledge of HPV and EGFR status can have implications for treatment options and prognosis in HNSCC. Cancer Epidemiol Biomarkers Prev; 20(6); 1230–7. ©2011 AACR.
The Association of Telomere Length and Cancer: a Meta-analysis
Authors: Wentzensen Ingrid M. , Mirabello Lisa , Pfeiffer Ruth M. , Savage Sharon A.
Published: June 2011

Background: Telomeres shorten with each cell division and are essential for chromosomal stability. Short telomeres in surrogate tissues (e.g., blood cells) are associated with increased cancer risk in several case–control studies, but findings are inconsistent in prospective studies.

Methods: We systematically reviewed studies published prior to August 30, 2010, on the association between telomere length (TL) in surrogate tissues and cancer. There were 27 reports on 13 cancers and/or incident cancer investigating this association. The majority, 16, were retrospective case–control studies, 11 were prospective studies. Meta-analyses were conducted to determine ORs and 95% CIs for these studies.

Results: Studies on bladder, esophageal, gastric, head and neck, ovarian, renal, and overall incident cancer found associations between short telomeres and these cancers. Non–Hodgkin lymphoma, breast, lung, and colorectal cancer reports were inconsistent. Single studies on endometrial, prostate, and skin cancers were null. In a random-effects meta-analysis, short TL was significantly associated with cancer in retrospective studies (pooled OR for the shortest TL quartile compared with the longest: 2.9, 95% CI: 1.75–4.8, P < 0.0001). The pooled OR for prospective studies was 1.16 (95% CI: 0.87–1.54, P = 0.32). All studies combined yielded a pooled OR of 1.96 (95% CI: 1.37–2.81, P = 0.0001) for the association of short TL and cancer.

Conclusion and Impact: There is suggestive evidence that short surrogate tissue TL is associated with cancer; the strongest evidence exists for bladder, esophageal, gastric, and renal cancers. Additional prospective studies with consistent methodology are needed to confirm this hypothesis. Cancer Epidemiol Biomarkers Prev; 20(6); 1238–50. ©2011 AACR.
TGF-β Signaling Pathway and Breast Cancer Susceptibility
Authors: Scollen Serena , Luccarini Craig , Baynes Caroline , Driver Kristy , Humphreys Manjeet K. , Garcia-Closas Montserrat , Figueroa Jonine , Lissowska Jolanta , Pharoah Paul D. , Easton Douglas F. , Hesketh Robin , Metcalfe James C. , Dunning Alison M.
Published: June 2011

Background: TGF-β acts as a suppressor of primary tumor initiation but has been implicated as a promoter of the later malignant stages. Here associations with risk of invasive breast cancer are assessed for single-nucleotide polymorphisms (SNP) tagging 17 genes in the canonical TGF-β ALK5/SMADs 2&3 and ALK1/SMADs 1&5 signaling pathways: LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, and SMAD7 [Approved Human Gene Nomenclature Committee gene names: ACVRL1 (for ALK1) and ENG (for Endoglin)].

Methods: Three-hundred-fifty-four tag SNPs (minor allele frequency > 0.05) were selected for genotyping in a staged study design using 6,703 cases and 6,840 controls from the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) study. Significant associations were meta-analyzed with data from the NCI Polish Breast Cancer Study (PBCS; 1,966 cases and 2,347 controls) and published data from the Breast Cancer Association Consortium (BCAC).

Results: Associations of three SNPs, tagging TGFB1 (rs1982073), TGFBR1 (rs10512263), and TGFBR2 (rs4522809), were detected in SEARCH; however, associations became weaker in meta-analyses including data from PBCS and BCAC. Tumor subtype analyses indicated that the TGFB1 rs1982073 association may be confined to increased risk of developing progesterone receptor negative (PR−) tumors [1.18 (95% CI: 1.09–1.28), 4.1 × 10−5 (P value for heterogeneity of ORs by PR status = 2.3 × 10−4)]. There was no evidence for breast cancer risk associations with SNPs in the endothelial-specific pathway utilizing ALK1/SMADs 1&5 that promotes angiogenesis.

Conclusion: Common variation in the TGF-β ALK5/SMADs 2&3 signaling pathway, which initiates signaling at the cell surface to inhibit cell proliferation, might be related to risk of specific tumor subtypes.

Impact: The subtype specific associations require very large studies to be confirmed. Cancer Epidemiol Biomarkers Prev; 20(6); 1112–9. ©2011 AACR.
Genetic and Viral Etiology of Glioblastoma—a Unifying Hypothesis
Authors: Pandey Janardan P.
Published: June 2011

Growing body of evidence implicates human cytomegalovirus (HCMV) in the etiology of glioblastoma (GBM). Although HCMV is a ubiquitous herpesvirus, only a minority of those infected develop GBM, suggesting the involvement of host genetic factors in susceptibility to HCMV-induced/spurred GBM. HCMV has evolved a large repertoire of strategies for decreasing the efficacy of the host immune response and interfering with viral clearance. One strategy involves the generation of proteins that have functional properties of the Fcgamma receptor (FcγR), which may enable the virus to evade host immunosurveillance by avoiding the effector consequences of antibody binding, such as antibody-dependent cellular cytotoxicity. Results of binding studies involving HCMV-encoded FcγR and genetically different immunoglobulin G proteins suggest that GM genes—genetic determinants of immunoglobulin γ chains—could modulate this viral strategy and thus serve as functional risk factors for the development of GBM, potentially unifying its seemingly disparate infectious, immune, and genetic etiologies. Cancer Epidemiol Biomarkers Prev; 20(6); 1061–3. ©2011 AACR.
Optical Coherence Tomographic Analysis of In-Stent Neoatherosclerosis After Drug–Eluting Stent Implantation
Authors: Kang Soo-Jin , Mintz Gary S. , Akasaka Takashi , Park Duk-Woo , Lee Jong-Young , Kim Won-Jang , Lee Seung-Whan , Kim Young-Hak , Whan Lee Cheol , Park Seong-Wook , Park Seung-Jung
Published: June 2011

Background—

We report findings from optical coherence tomography (OCT) of in-stent neoatherosclerosis as a cause of drug-eluting stent (DES) failure.

Methods and Results—

Optical coherence tomography and grayscale and virtual histology intravascular ultrasound were performed in 50 patients (30 stable, 20 unstable angina) with 50 DES in-stent restenosis lesions and intimal hyperplasia >50% of stent area. Median follow-up time was 32.2 months. Overall, 26 lesions (52%) had at least 1 OCT-defined in-stent thin-cap fibroatheroma (TCFA)–containing neointima and 29 (58%) had at least 1 in-stent neointimal rupture. Patients presenting with unstable angina showed a thinner fibrous cap (55 μm [interquartile range 42 to 105 μm] versus 100 μm [interquartile range 60 to 205 μm],
P
=0.006) and higher incidence of OCT-defined TCFA-containing neointima (75% versus 37%,
P
=0.008), intimal rupture (75% versus 47%,
P
=0.044), thrombi (80% versus 43%,
P
=0.010), and red thrombi (30% versus 3%,
P
=0.012) than stable patients. Fibrous cap thickness negatively correlated with follow-up time (
r
=−0.318,
P
=0.024). Compared with DES <20 months after implantation (the best cut-off to predict TCFA-containing neointima), DES ≥20 months after implantation had a higher incidence of TCFA-containing neointima (69% versus 33%,
P
=0.012) and red thrombi (27% versus 0%,
P
=0.007). Patients with unstable (versus stable) angina had an increasing number of unstable OCT findings including TCFA-containing neointima, neointima rupture, and thrombus (
P
=0.027). The rate of agreement between grayscale intravascular ultrasound and OCT for detecting intimal rupture was 50% and for detecting thrombus was 44%. The agreement between virtual histology intravascular ultrasound and OCT for identifying TCFA-containing neointima was 78%.

Conclusions—

In-stent neoatherosclerosis may be an important mechanism of DES failure, especially late after implantation.
High-Resolution Simulations of Wintertime Precipitation in the Colorado Headwaters Region: Sensitivity to Physics Parameterizations
Authors: Liu Changhai , Ikeda Kyoko , Thompson Gregory , Rasmussen Roy , Dudhia Jimy
Published: June 2011

An investigation was conducted on the effects of various physics parameterizations on wintertime precipitation predictions using a high-resolution regional climate model. The objective was to evaluate the sensitivity of cold-season mountainous snowfall to cloud microphysics schemes, planetary boundary layer (PBL) schemes, land surface schemes, and radiative transfer schemes at a 4-km grid spacing applicable to the next generation of regional climate models.

The results indicated that orographically enhanced precipitation was highly sensitive to cloud microphysics parameterizations. Of the tested 7 parameterizations, 2 schemes clearly outperformed the others that overpredicted the snowfall amount by as much as ~30%–60% on the basis of snow telemetry observations. Significant differences among these schemes were apparent in domain averages, spatial distributions of hydrometeors, latent heating profiles, and cloud fields. In comparison, model results showed relatively weak dependency on the land surface, PBL, and radiation schemes, roughly in the order of decreasing level of sensitivity.
Social determinants of crime in a welfare state: Do they still matter?
Authors: Aaltonen Mikko , Kivivuori Janne , Martikainen Pekka
Published: June 2011

Despite decades of research on the association between socio-economic status (SES) and crime, its strength and nature remain contested. Using a unique dataset combining data from several administrative registers with a nationally representative sample of 28,485 19 to 30-year-old Finnish citizens, we examine SES differences in violent offences, property offences and driving while intoxicated. We use multiple measures of SES in order to see what it is in SES that increases crime risk. We also test the strain accumulation hypothesis to find out whether presence of multiple strains increases crime risk disproportionately. The results indicate that, in addition to male gender, SES is strongly associated with all three types of crime, and the predictors are largely similar for all the offence types in question. Long-term unemployment and having only a basic education, in particular, were the most robust predictors of offending. These associations held after controlling for previous criminal involvement as well as other social characteristics, whereas the effect of low income on crime was primarily attributable to prior involvement in crime. Overall, the results imply that there are both causation and selection mechanisms at play. No interactive effect was found for strain accumulation.
Pertinence de la théorie de la dualisation de la religion en Suisse, en France et en Europe
Authors: Bréchon Pierre , Campiche Roland J.
Published: June 2011

Les grandes explications relatives au changement religieux contemporain se heurtent à deux écueils. D’une part, elles ne parviennent souvent pas à exprimer la complexité de l’évolution en cours, focalisées qu’elles sont sur la religion institutionnelle. C’est souvent le cas des théories de la sécularisation. D’autre part, certaines théories privilégient les thèmes à la mode (montée de l’individualisme, privatisation du religieux) et escamotent l’impact sociétal de la religion. Le concept de dualisation de la religion permet une saisie conjointe du processus de désinstitutionnalisation de la religion et des modalités nouvelles de sa régulation. Les auteurs vérifient l’hypothèse de la dualisation à partir des données disponibles (EVS, ISSP) pour la Suisse, la France et une partie de l’Europe de l’Ouest. Malgré la difficulté de trouver des indicateurs pertinents et comparables, les résultats sont probants. Ils incitent à une analyse critique des items couramment utilisés. La théorie de la dualisation permet ainsi de relancer le débat sur le changement religieux.
The Making of Religious Pluralism in Italy: Discussing Religious Education from a New Generational Perspective
Authors: Frisina Annalisa
Published: June 2011

Italian society continues to be seen as homogeneous in religious terms and the teaching of Catholic religion in state schools as a pillar of the historical and cultural heritage of the Italian population, as sanctioned by the 1984 Concordat between the State and the Catholic Church. But profound changes have been under way since that Concordat, with migrant families settling in the country and their Italian-born offspring now attending Italian state schools. How do they feel about religious education at school? How do they view the Italian model of secularism and religious pluralism in Italy? What do they see as Italianness? A qualitative, focus-group-based investigation into secondary schools in a northern Italian town enables us to bring out these students’ demand for change from a generational standpoint and see beyond education into religion to possible ways to educate about and from religions, creating new horizons for religious pluralism (even) in Italy.
Housing Densities and Consumer Choice
Authors: Evans Alan , Unsworth Rachael
Published: June 2011

From 2001, the construction of flats and high-density developments increased in England and the building of houses declined. Does this indicate a change in taste or is it a result of government planning policies? In this paper, an analysis is made of the long-term effects of the policy of constraint which has existed for the past 50 years but the increase in density is identified as occurring primarily after new, revised, planning guidance was issued in England in 2000 which discouraged low-density development. To substantiate this, it is pointed out that the change which occurred in England did not occur in Scotland where guidance was not changed to encourage high-density residential development. The conclusion that the change is the result of planning policies and not of a change in taste is confirmed by surveys of the occupants of new high-rise developments in Leeds. The new flat-dwellers were predominantly young and childless and expressed the intention, in the near future, when they could, of moving out of the city centre and into houses. From recent changes in guidance by the new coalition government, it is expected that the construction of flats in England will fall back to earlier levels over the next few years.
Form Follows Function? Linking Morphological and Functional Polycentricity
Authors: Burger Martijn , Meijers Evert
Published: June 2011

Empirical research establishing the costs and benefits that can be associated with polycentric urban systems is often called for but rather thin on the ground. In part, this is due to the persistence of what appear to be two analytically distinct approaches in understanding and measuring polycentricity: a morphological approach centring on nodal features and a functional approach focused on the relations between centres. Informed by the oft-overlooked but rich heritage of urban systems research, this paper presents a general theoretical framework that links both approaches and discusses the way both can be measured and compared in a coherent manner. Using the Netherlands as a test case, it is demonstrated that most regions tend to be more morphologically polycentric than functionally polycentric. The difference is largely explained by the size, external connectivity and degree of self-sufficiency of a region’s principal centre.