bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Al2O3 sol concentration on the microstructure and mechanical properties of Cu–Al2O3 composite coatings
Authors: Wei Xiaojin , Yang Zhendi , Tang Ying , Gao Wei
Published: April 2015

Copper ( Cu ) is widely used as electrical conducting and contacting material. However, Cu is soft and does not have good mechanical properties. In order to improve the hardness and wear resistance of Cu , sol-enhanced Cu – Al 2 O 3 nanocomposite coatings were electroplated by adding a transparent Al oxide ( Al 2 O 3) sol into the traditional electroplating Cu solution. It was found that the microstructure and mechanical properties of the nanocomposite coatings were largely influenced by the Al 2 O 3 sol concentration. The results show that the Al 2 O 3 nanoparticle reinforced the composite coatings, resulting in significantly improved hardness and wear resistance in comparison with the pure Cu coatings. The coating prepared at the sol concentration of 3.93 mol/L had the best microhardness and wear resistance. The microhardness has been improved by ~20% from 145.5 HV (Vickers hardness number) of pure Cu coating to 173.3 HV of Cu – Al 2 O 3 composite coatings. The wear resistance was also improved by ~84%, with the wear volume loss dropped from 3.2 × 10-3 mm3 of Cu coating to 0.52 × 10-3 mm3 of composite coatings. Adding excessive sol to the electrolyte deteriorated the properties.
Recovery of silver metal from low concentrated wastewater by photocatalysis
Authors: Ding Mali , Han Jie , Qiu Wei , Zhang Weijun , Gao Wei
Published: April 2015

This work studies the photocatalytic activity of zinc oxide ( ZnO ) nanopowder to recover silver ( Ag ) metal from low Ag + concentrated solution under artificial ultraviolet (UV) light. Benchmark titanium dioxide (P25 TiO 2) was used for comparison purpose. Experimental results indicated that ZnO exhibited superior performance for Ag recovery compared to TiO 2. Under optimal catalyst loading, the achieved Ag removal efficiencies were 100% and 99.94% at 0.2 g/L ZnO (1 h) and 2 g/L TiO 2 (2 h), respectively. An induction period at low concentration of TiO 2 (0.1 g/L) was observed and a mechanism was proposed. The photodissolution of ZnO was assessed and proved to be negligible. Recovered pure Ag metal was characterized by X-ray diffractometry (XRD) and scanning electron microscopy (SEM), showing a promising effective Ag recovery technology using ZnO photocatalyst.
Thermal radiation characteristics of silicon inverse opal in mid infrared range
Authors: Xu Jing , Xie Kai
Published: April 2015

A binary solvent with large density was used as dispersant for silica spheres, in which silica spheres with large diameter can suspend steadily and disperse very well. With this suspension, fine opals with 2100 nm SiO 2 mono-disperse spheres were successfully prepared by solvent evaporation method. Low pressure vapor deposition method was then used to fill the voids of the silica opals with Si , and silicon inverse opal with photonic band gaps in mid infrared region was obtained. The infrared radiation characteristic of resulted sample was examined. It is shown that silicon inverse opal structure is effective in suppressing silicon thermal radiation in the photonic band gap spectral region.
Analysis of thin strip profile by work roll crossing and shifting in asymmetrical cold rolling
Authors: Aljabri Abdulrahman , Jiang Zhengyi , Wei Dongbin
Published: April 2015

In order to analyze the effects of cold rolling parameters such as the crossing angle and axial shifting value of work rolls on the strip profile, extensive tests were carried out on a 4-high rolling mill equipped with a work roll crossing and shifting system. The results show that the strip profile is nearly flat under asymmetrical rolling. The rolling force was also analyzed in detail by changing the crossing angle and axial shifting value of work rolls.
A Knowledge Preservation and Re-Use Tool Based on Context-Driven Reasoning
Authors: Gonzalez Avelino J. , Sherwell Brian , Nguyen Johann , Becker Brian C. , Hung Víctor , Brezillon Patrick
Published: April 2015

This article describes a knowledge preservation and re-use tool designed to capture the knowledge of a specific individual at the US National Science Foundation, for later retrieval by successors after his retirement. The system is designed in a Q&A format, where it is sufficiently intelligent to ask for clarifying questions. The primary objective was to create a system that would result in acceptance of the system by the users. The domain of interest to be preserved and re-used was programmatic knowledge about the NSF Industry/University Collaborative Research Centers (I/UCRC) Program, and more specifically, the knowledge of its long-time director, Dr. Alex Schwarzkopf. The system is called AskAlex and it uses a trio of techniques to accomplish its objectives. Contextual graphs (CxG) are used as the basic knowledge representation structure. CxG’s are assisted by a search engine and an ontology of terms to help find the proper contextual graph that can best answer the question being asked. Evaluations with users and potential users generally confirm our selection and provided some guidance for improvements in the system.
A Hybrid Meta-Heuristic Algorithm for Vehicle Routing Problem with Time Windows
Authors: Yassen Esam Taha , Ayob Masri , Ahmad Nazri Mohd Zakree , Sabar Nasser R.
Published: April 2015

Harmony search algorithm, which simulates the musical improvisation process in seeking agreeable harmony, is a population based meta-heuristics algorithm for solving optimization problems. Although it has been successfully applied on various optimization problems; it suffers the slow convergence problem, which greatly hinders its applicability for getting good quality solution. Therefore, in this work, we propose a hybrid meta-heuristic algorithm that hybridizes a harmony search with simulated annealing for the purpose of improving the performance of harmony search algorithm. Harmony search algorithm is used to explore the search spaces. Whilst, simulated annealing algorithm is used inside the harmony search algorithm to exploit the search space and further improve the solutions that are generated by harmony search algorithm. The performance of the proposed algorithm is tested using the Solomon's Vehicle Routing Problem with Time Windows (VRPTW) benchmark. Numerical results demonstrate that the hybrid approach is better than the harmony search without simulated annealing and the hybrid also proves itself to be more competent (if not better on some instances) when compared to other approaches in the literature.
Lovelock black holes in the presence of nonlinear electrodynamics
Authors: Hendi Seyed Hossein
Published: April 2015

In this paper, we consider third-order Lovelock–Maxwell gravity with additional (Fμν Fμν)2 term as a nonlinearity correction of the Maxwell theory. We obtain black hole solutions with various horizon topologies (and various number of horizons) in which their asymptotical behavior can be flat or anti-de Sitter with an effective cosmological constant. We investigate the effects of Lovelock and electrodynamic corrections on properties of the solutions. Then, we restrict ourselves to asymptotically flat solutions and calculate the conserved and thermodynamic quantities. We check the first law of thermodynamics for these black hole solutions and calculate the heat capacity to analyze stability. Although higher dimensional black holes in Einstein gravity are unstable, here we look for suitable constraints on the black hole radius to find thermally stable black hole solutions.
A Multichannel Surface EMG System for Hand Motion Recognition
Authors: Fang Yinfeng , Liu Honghai , Li Gongfa , Zhu Xiangyang
Published: April 2015

Surface electromyography (sEMG)-based hand motion recognition has a variety of promising applications. While a person performs different hand motions, commands can be extracted to control external devices, such as prosthetic hands, tablets and so forth. The acquisition of discriminative sEMG signals determines the accuracy of intended control commands extraction. This paper develops an 16-channel sEMG signal acquisition system with a novel electrode configuration that is specially designed to collect sEMG on the forearm. Besides, to establish the relationship between multichannel sEMG signals and hand motions, a 2D EMG map is designed. Inspired from the electromyographic (EMG) map, this paper proposes an EMG feature named differential root mean square (DRMS) that somewhat takes the relationship between neighboring EMG channels into account. In the task of four hand motion discrimination by K-means and fuzzy C-means, DRMS outperforms traditional root mean square (RMS) by 29.0% and 36.8%, respectively. The findings of this paper support and guide the use of sEMG techniques to investigate sEMG-based hand motion recognition.
A Novel Algorithm for Detection and Classification of Brain Tumors
Authors: Jobin Christ M. C. , Gao X. Z. , Zenger Kai
Published: April 2015

Segmentation of an image is the partition or separation of the image into disjoint regions of related features. In clinical practice, magnetic resonance imaging (MRI) is used to differentiate pathologic tissues from normal tissues, especially for brain tumors. The main objective of this paper is to develop a system that can follow a medical technician way of work, considering his experience and knowledge. In this paper, a step by step methodology for the automatic MRI brain tumor segmentation and classification is presented. Initially acquired MRI brain images are preprocessed by the Gaussian filter. After preprocessing, initial segmentation is done by hierarchical topology preserving map (HTPM). From the resultant images, the features are extracted using gray level co-occurrence matrix (GLCM) method, and the same are given as inputs to adaptive neuro fuzzy inference systems (ANFIS) for final segmentation and the classification of brain images into normal or abnormal. In case of abnormal, the MRI brain images are classified as benign subject (tumor without cancerous tissues) or malignant subject (tumor with cancerous tissues). Based on the analysis, it has been discovered that the overall accuracy of classification of our method is above 94%, and F1-score is about 1. The simulation results also show that the proposed approach is a valuable diagnosing technique for the physicians and radiologists to detect the brain tumors.
Cellulose acetate–lithium bis(trifluoromethanesulfonyl)imide solid polymer electrolyte: ATR-FTIR and ionic conductivity behavior
Authors: Mohd Razalli Siti Masyitah , Sheikh Mohd Saaid Siti Irma Yuana , Marwan Ali Ab Malik , Hassan Oskar Hasdinor , Yahya Muhd Zu Azhan
Published: April 2015

Solid polymer electrolytes (SPEs) based on cellulose acetate (CA) doped with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt are prepared by solution cast technique. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy of the polymer salt complexes are recorded in the frequency range between 400 cm-1 and 4000 cm-1. The shifting of carbonyl band ( C=O ) at 1737 cm-1 to a lower wavenumber confirms the occurrence of complexation between the polymer and the salt. The electrochemical impedance spectroscopy (EIS) analysis discovered that the film with 25 wt.% of salt shows the highest ionic conductivity at room temperature. The change in real dielectric permittivity (εr) as a function of frequency at different salt concentrations which exhibits a dispersive behavior at low frequencies and decays at higher frequencies, shows the electrode polarization and space charge effect. The real modulus formalism (Mr) analysis shows that the polymer electrolytes in this work are ionic conductors.
Study on properties of tantalum-dopedLa2Ti2O7ferroelectric ceramics
Authors: Li Chunchun , Khaliq Jibran , Ning Huanpo , Wei Xiaoyong , Yan Haixue , Reece Michael J.
Published: April 2015

A series of ceramics with a general formula, La2Ti2-xTaxO7, in which x = 0.05, 0.1, 0.2, and 0.3, were prepared by Spark Plasma Sintering (SPS). Effects of tantalum substitution for titanium on the structure, dielectric, and piezoelectric properties were studied. Results revealed that the structure changed gradually from 4-layer to 3-layer due to the higher valence of Ta . The solid solution limit of tantalum in La2Ti2O7lattice was in the proximity of x = 0.2. The ferroelectric Curie temperature (Tc) decreased with increasing tantalum doping content. dc resistivity reached a maximum value at x = 0.2 with a value of ∼ 1.0 × 108Ω ⋅ cm at 600°C. The influence of texture on the piezoelectric properties of La2Ti2-xTaxO7ceramics was also investigated. A maximum d33value ∼2.1 pC/N was obtained at x = 0.2.
Can Structural Models Price Default Risk? Evidence from Bond and Credit Derivative Markets
Authors: Ericsson Jan , Reneby Joel , Wang Hao
Published: April 2015

Using a set of structural models, we evaluate the price of default protection for a sample of US corporations. In contrast to previous evidence from corporate bond data, credit default swap (CDS) premia are not systematically underestimated. In fact, one of our studied models has little difficulty on average in predicting their level. For robustness, we perform the same exercise for bond spreads by the same issuers on the same trading date. As expected, bond spreads relative to the treasury curve are systematically underestimated. This is not the case when the swap curve is used as a benchmark, suggesting that previously documented underestimation results may be sensitive to the choice of risk-free rate.
Bilateral counterparty risk valuation adjustment with wrong way risk on collateralized commodity counterparty
Authors: Yang Yifan , Fabozzi Frank J. , Bianchi Michele Leonardo
Published: April 2015

Basel III requires banks to include a credit value adjustment (CVA) into capital charges. Both CVA and debt value adjustment (DVA) must be included for derivatives using mark-to-market accounting. An effective method to calculate bilateral-CVA (BR-CVA) by incorporating wrong-way risk (WWR) for a collateralized counterparty is proposed which handles WWR — defined as when counterparty credit exposure increases as default probability increases — by building a trivariate Gaussian copula between the aggregate market risk exposure factor and default quality of the financial institution and counterparty. This paper extends the ordered-scenario copula model proposed in the literature. It links BR-CVA pricing and WWR, which is close to the current regulatory requirement and useful for managing a financial institution's risk. A practical example is provided. Numerical results suggest that the proposed method is efficient and robust and can easily stress test the impact of WWR in BR-CVA pricing.
The depositional environment of the Ashfell Sandstone Formation (Arundian, Mississippian), Ash Fell Edge, Cumbria, NW England
Authors: Stanway P. , Nudds J. , Broadhurst F.
Published: April 2015

The depositional environment of the upper strata of the Ashfell Sandstone Formation in east Cumbria is investigated. By recording the sedimentary sequence, we have determined a series of facies and facies associations from which we have interpreted the conditions of sedimentation during late Arundian (Visean, Mississippian) times. The most likely interpretation is that sedimentation occurred in a shallow equatorial sea, close to a shoreline, and possibly in a lagoon environment that was subject to periodic monsoonal storms.
Preservation of a fragmented late Neoproterozoic–earliest Cambrian hyper-extended continental-margin sequence in the Australian Delamerian Orogen
Authors: Gibson G. M. , Champion D. C. , Ireland T. R.
Published: April 2015

Mafic and ultramafic rocks intercalated with metamorphosed deep-marine sediments in the Glenelg River Complex of SE Australia comprise variably tectonized fragments of an interpreted late Neoproterozoic–earliest Cambrian hyper-extended continental margin that was dismembered and thrust westwards over the adjacent continental margin during the Cambro-Ordovician Delamerian Orogeny. Ultramafic rocks include serpentinized harzburgite of inferred subcontinental lithospheric origin that had already been exhumed at the seafloor before sedimentation commenced, whereas mafic rocks exhibit mainly enriched- and normal-type mid-ocean ridge basalt (E- and N-MORB) compositions consistent with emplacement in an oceanic setting. These lithologies and their metasedimentary host rocks predate deposition of the Cambrian Kanmantoo Group and are more likely to represent temporal equivalents of the older Normanville Group or underlying Neoproterozoic Adelaide Supergroup. The Kanmantoo Group is host to basaltic rocks with higher degrees of crustal contamination and yields detrital zircon populations dominated by 600–500 Ma ages. Except for quartz greywacke confined to the uppermost part of the sequence, metasedimentary rocks in the Glenelg River Complex are devoid of detrital zircon, and are interstratified with subordinate amounts of metachert and carbonaceous dolomitic slate suggestive of deposition in a deep-marine environment far removed from any continental margin. Seismic reflection data support the idea that the Glenelg River Complex is underlain by mafic and ultramafic rocks, and preclude earlier interpretations based on aeromagnetic data that the continental margin incorporates a thick pile of seawards-dipping basaltic flows analogous to those of volcanic margins in the North Atlantic. Correlative hyper-extended continental rift margins to the Glenelg River Complex occur along strike in formerly contiguous parts of Antarctica.

Supplementary material:

Geochemical data for mafic and ultramafic rocks in the Glenelg River Complex and correlative terranes, and U–Th–Pb data for western Victoria gabbros are available at
http://www.geolsoc.org.uk/SUP18821
When Location Meets Social Multimedia
Authors: Ji Rongrong , Gao Yue , Liu Wei , Xie Xing , Tian Qi , Li Xuelong
Published: April 2015

Coming with the popularity of multimedia sharing platforms such as Facebook and Flickr, recent years have witnessed an explosive growth of geographical tags on social multimedia content. This trend enables a wide variety of emerging applications, for example, mobile location search, landmark recognition, scene reconstruction, and touristic recommendation, which range from purely research prototype to commercial systems. In this article, we give a comprehensive survey on these applications, covering recent advances in recognition and mining of geographical-aware social multimedia. We review related work in the past decade regarding to location recognition, scene summarization, tourism suggestion, 3D building modeling, mobile visual search and city navigation. At the end, we further discuss potential challenges, future topics, as well as open issues related to geo-social multimedia computing, recognition, mining, and analytics.
Secure Your Data and Compute on It, Too
Authors: Rosulek Mike
Published: April 2015

Modern cryptography provides techniques to perform useful computations on sensitive data.
The Wrens of Bletchley Park
Authors: Smith Michael
Published: April 2015

The lives and times of the British women who operated Colossus, and their all-important role in events leading to D-Day and the close of the Second World War.
Kristin Lauter on Cryptography and Mathematics
Authors: Agrawal Shashank , Rathje Billy
Published: April 2015

There are unique challenges posed by cryptography research. This interview examines potential threats to modern security techniques and how to overcome them.
Beyond Dominant Resource Fairness
Authors: Parkes David C. , Procaccia Ariel D. , Shah Nisarg
Published: April 2015

We study the problem of allocating multiple resources to agents with heterogeneous demands. Technological advances such as cloud computing and data centers provide a new impetus for investigating this problem under the assumption that agents demand the resources in fixed proportions, known in economics as
Leontief
preferences
. In a recent paper, Ghodsi et al. [2011] introduced the
dominant resource fairness
(DRF) mechanism, which was shown to possess highly desirable theoretical properties under Leontief preferences. We extend their results in three directions. First, we show that DRF generalizes to more expressive settings, and leverage a new technical framework to formally extend its guarantees. Second, we study the relation between social welfare and properties such as truthfulness; DRF performs poorly in terms of social welfare, but we show that this is an unavoidable shortcoming that is shared by every mechanism that satisfies one of three basic properties. Third, and most importantly, we study a realistic setting that involves indivisibilities. We chart the boundaries of the possible in this setting, contributing a new relaxed notion of fairness and providing both possibility and impossibility results.
Budget allocations for hierarchical fixed-priority scheduling of sporadic tasks with deferred preemptions upon EDP resources
Authors: van den Heuvel Martijn M. H. P. , Bril Reinder J. , Lukkien Johan J.
Published: April 2015

In this paper we revisit the admission of applications upon a processor share modeled by the explicit-deadline periodic (EDP) resource-supply model. In particular, we consider applications that represent a fixed-priority sporadic task system. Existing works heavily build on the analysis of a hierarchy of preemptive task schedulers. We instead consider the feasibility of such tasks and applications for a hierarchy of deferred-preemptive schedulers, so that we can efficiently deal with the scenario where tasks and applications execute their work in non-preemptive chunks. Our model therefore gives better control over preemptions of tasks of different applications.

We present exact analysis for deferred-preemptive scheduling of tasks on EDP resources. In addition, we propose algorithms for dimensioning an application's budget tightly.
Exploring the Universe
Authors: Schmidt Maarten
Published: April 2015

I cover my life and career, first in Holland during World War II and then in Pasadena, California, after we emigrated in 1959. My main work concerned the rate of star formation and the discovery of quasars and their cosmological evolution. It's a great honor to write an essay for this volume of the Annual Review of Astronomy and Astrophysics. It is primarily an autobiography with an attempt to link my own career to some of the major developments in astronomy.
Citrate-Based Biomaterials and Their Applications in Regenerative Engineering
Authors: Tran Richard T. , Yang Jian , Ameer Guillermo A.
Published: April 2015

Advances in biomaterials science and engineering are crucial to translating regenerative engineering, an emerging field that aims to recreate complex tissues, into clinical practice. In this regard, citrate-based biomaterials have become an important tool owing to their versatile material and biological characteristics including unique antioxidant, antimicrobial, adhesive, and fluorescent properties. This review discusses fundamental design considerations, strategies to incorporate unique functionality, and examples of how citrate-based biomaterials can be an enabling technology for regenerative engineering.
Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Authors: Sandoval Darleen A. , D'Alessio David A.
Published: April 2015

The preproglucagon gene ( Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set of neurons within the nucleus of the solitary tract. Gcg encodes multiple peptides including glucagon, glucagon-like peptide-1, glucagon-like peptide-2, oxyntomodulin, and glicentin. Of these, glucagon and GLP-1 have received the most attention because of important roles in glucose metabolism, involvement in diabetes and other disorders, and application to therapeutics. The generally accepted model is that GLP-1 improves glucose homeostasis indirectly via stimulation of nutrient-induced insulin release and by reducing glucagon secretion. Yet the body of literature surrounding GLP-1 physiology reveals an incompletely understood and complex system that includes peripheral and central GLP-1 actions to regulate energy and glucose homeostasis. On the other hand, glucagon is established principally as a counterregulatory hormone, increasing in response to physiological challenges that threaten adequate blood glucose levels and driving glucose production to restore euglycemia. However, there also exists a potential role for glucagon in regulating energy expenditure that has recently been suggested in pharmacological studies. It is also becoming apparent that there is cross-talk between the proglucagon derived-peptides, e.g., GLP-1 inhibits glucagon secretion, and some additive or synergistic pharmacological interaction between GLP-1 and glucagon, e.g., dual glucagon/GLP-1 agonists cause more weight loss than single agonists. In this review, we discuss the physiological functions of both glucagon and GLP-1 by comparing and contrasting how these peptides function, variably in concert and opposition, to regulate glucose and energy homeostasis.
The Role of Geographic Factors in Human Papillomavirus (HPV) Vaccine Uptake Among Adolescent Girls in the United States
Authors: Henry KA , Warner EL , Ding Q , Kepka D
Published: April 2015

There has been limited research examining the role of geographic factors in human papillomavirus (HPV) vaccine uptake among adolescent girls. This study is one of the first to investigate and identify community-level geographic factors that may be associated with HPV vaccine uptake in the United States. We analyzed data from the 2011 and 2012 National Immunization Survey-Teen to examine associations of HPV vaccine initiation (receipt of at least one dose based on healthcare provider records) among female adolescents aged 13 to 17 years (N = 20,565) with ZIP code level geographic factors that were linked to the survey. Analyses were conducted using weighted logistic regression that included state-random effects. HPV vaccine initiation was approximately 53% in both 2011 and 2012. Racial composition and urban/rural residence were both independently associated with vaccine initiation (P = < 0.05). Initiation was higher among girls living in communities where the majority (>50%) of the population was Hispanic compared to communities where the majority of the population was non-Hispanic white (69.0% vs 49.9%; Adjusted Odds Ratio (AOR) 1.55, 95% CI, 1.33–1.80). Girls living in high population density areas (urban) had higher HPV vaccine initiation compared to those living in low population density areas (rural) (56% vs 44.6%; AOR 1.37, 95% CI, 1.13–1.65). Initiation was also higher among girls living in the most impoverished communities compared to girls living in the least impoverished communities (61% vs 50.4%), but community-level poverty was not significant in the adjusted analysis. Higher HPV vaccination coverage in poor urban communities with a high proportion of racial/ethnic minorities may be partly attributable to targeted interventions and the continued effectiveness of the Vaccines for Children program (VFC), which provides recommended vaccines at no cost to eligible children. Learning more about factors that influence higher HPV vaccination initiation rates among certain groups might inform intervention strategies for groups with lower initiation rates.
Cervical Cancer Prevention Services at College Health Centers: Historically Black Colleges and Universities (HBCUs) Compared to Predominantly White Institutions (PWIs)
Authors: Barnett KB , McRee AL , Reiter PL , Paskett ED , Katz ML
Published: April 2015

Cervical cancer (CC) incidence and mortality rates are increased among African American women. We sought to examine the availability of CC prevention services, such as the HPV vaccine and Pap tests, at college health centers among Historically Black Colleges and Universities (HBCUs) compared to Predominantly White Institutions (PWIs). Methods: We analyzed data from a sample of colleges and universities identified using the National Center for Education Statistics' College Navigator tool. Identified HBCUs were matched with a randomly selected four year PWI within the same state, resulting in an analytic sample of 162 colleges and universities. We collected data on health services and institutional characteristics via the institutions' websites, the College Navigator Tool, and by telephone interviews with health centers. We examined whether institutions provided HPV vaccine or Pap tests to students and identified correlates of each using logistic regression. Results: A total of 131 (81%) colleges and universities had operating health centers, of which 121 (92%) were successfully contacted via telephone. HBCUs were less likely than PWIs to offer the HPV vaccine (21% vs.46%; p-value < 0.05) or Pap tests (49% vs. 67%; p-value <0.05). However, in multivariate logistic regression models, the difference was no longer statistically significant. Significant variables were setting (non- rural vs. rural) and enrollment size. Institutions in a non-rural setting (OR = 4.42; 95% CI, 1.01–19.42) were more likely to offer the HPV vaccine, and institutions with higher enrollments (per every 1,000 increase) were more likely to offer the HPV vaccine (OR = 1.24; 95% CI, 1.10–1.39) or Pap tests (OR = 1.18; 95% CI, 1.0–1.39) to students. Conclusion: Many colleges and universities are not offering the HPV vaccine or Pap tests to students. Student enrollment size and non-rural setting of the institution are important determinants of whether a college or university offers CC prevention services. Given that HBCUs support a large concentration of minority students who are at risk of cervical cancer, a greater effort should be employed at these smaller institutions to increase the availability of CC prevention services.
Factors Affecting Informed Decision-Making in Women with Increased Breast Cancer Risk or DCIS Pursuing Contralateral Prophylactic Mastectomy
Authors: Valente J , Stybio T , Hyde S , Lipscomb J , Gillespie TW
Published: April 2015

Despite lack of survival benefit, an increasing number of women diagnosed with ductal carcinoma in situ (DCIS) opt for removal of the unaffected breast in addition to the breast with known pathology, i.e. contralateral prophylactic mastectomy (CPM). Little is known about women's decision-making processes that contribute to this rising trend, particularly for DCIS. Further obscuring the decision is the highly variable terminology used to discuss breast cancer pathologies and treatments. The purpose of this study was to investigate factors impacting risk comprehension and decision-making related to increased risk for breast cancer or DCIS. We conducted a retrospective and prospective pilot study to evaluate women's perceived contralateral breast cancer risk, health literacy, numeracy, and comprehension of terms used in genetics and breast cancer. Clinical data such as breast MRI, genetic testing, family history, and breast cancer risk derived from predictive models were also collected. Women with DCIS and those high-risk for development of invasive breast cancer were eligible, and 68 patients participated. Of the cohort, 33 (48.5%) women considered pursuing CPM and 11 (16.2%) underwent CPM. Anxiety about cancer recurrence was the top reason for considering CPM. Undergoing CPM was significantly associated with plastic surgery consultation, increased 10-year breast cancer risk, genetic counseling, and genetic testing. The consideration of CPM was also associated with higher incomes. Numeracy, health and genetic literacy, and terminology scores were not significant predictors of CPM. Lastly, 83.8% of respondents stated DCIS qualified as breast cancer, but only 39.7% of patients correctly defined DCIS. When asked to interpret the phrase “indolent lesion of epithelial origin” (new terminology advocated to replace “DCIS”), 27.9% of respondents believed it referred to cancer, 47.1% did not, and 23.5% were unsure. Patients commonly thought “lesion” meant “skin wound” or “sore”. Decision-making related to DCIS remains complex. Although CPM has not shown a survival advantage and can have significant complications, CPM rates continue to rise. Recognizing patients' knowledge of risk communication and terminology is vital to support shared and informed surgical decisions.
Depression and Antidepressant Use in Relation to Breast Cancer Risk in the Nurses Health Study
Authors: Reeves KW , Okereke O , Qian J , Hankinson SE
Published: April 2015

Depression and antidepressant (AD) use have each been hypothesized to increase breast cancer risk, yet previous studies have not considered these exposures together. Thus, it is unclear whether increased risk due to depression may actually be attributable to AD use, or vice versa. Methods: We utilized data from 77,482 women enrolled in the prospective Nurses' Health Study cohort in which data on depression and AD use were collected simultaneously beginning in 2000. Women self-reported whether they had ever been diagnosed with depression by a clinician as well as their use of specific types of ADs. Self-reported breast cancer cases through 2012 were adjudicated and only confirmed invasive cases included as outcomes (N = 2,567). Logistic regression models were utilized to evaluate the effects of baseline depression and AD use, both independently and with mutual adjustment, on breast cancer risk. Results: The average age of participants was 66.2 (SD 7.1) years; 8.9% were clinically depressed and 8.7% used ADs. In separate models adjusted for age, body mass index, and menopausal status, we observed no statistically significant associations between depression (OR 0.94, 95% CI, 0.81–1.08) or AD use (OR 1.07, 95% CI, 0.93–1.22). When these exposures were included together in the same model, depression remained unassociated with breast cancer risk (OR 0.87, 95% CI, 0.74–1.03) while AD use exhibited a small, borderline significant increase in risk (OR 1.15, 95% CI, 0.98–1.35). The latter association remained consistent for selective serotonin reuptake inhibitors (SSRIs; OR 1.16, 95% CI, 0.96–1.39) but was not apparent for other classes of ADs (OR 1.07, 95% CI, 0.85–1.35). Conclusions: These initial results indicate that depression is not associated with breast cancer risk, while we could not exclude a slight increase in risk associated with SSRI use. Further analyses will update exposure information over follow-up and also evaluate whether associations differ by menopausal status or hormone receptor disease subtypes. Clarifying the effects of these exposures on breast cancer risk will provide critical information for the millions of women who are depressed and/or use ADs.
Can the “Hispanic Paradox” Shed Light on Childhood Cancer Risk?
Authors: Heck JE , Park AS , Cockburn M , Ritz B
Published: April 2015

The “Hispanic epidemiologic paradox” is the commonly observed phenomenon that foreign-born Hispanic mothers who emigrate to the United States have consistently good pregnancy outcomes, such as decreased rates of low birthweight, despite high levels of poverty. We examined whether this advantage extends to childhood cancer risk. Methods: The study included all children born in California from 1983–2007. Birthrolls were linked to California Cancer Registry records of children ages <6 who were diagnosed with cancer 1988–2007 (N = 8710 cases, 9,519,438 controls). The mother's Hispanic origin, ethnic ancestry, and country of birth were ascertained from the birth certificate. We used Cox proportional hazard models to estimate the risk for cancer based upon maternal birthplace and ethnic ancestry. Models stratified by tumor subtype and adjusted for maternal and paternal age. Summary of results: The children of foreign-born Hispanic women had lower rates of several cancers [acute lymphoblastic leukemia (ALL; odds ratio (OR) = 1.05, 95% confidence interval (CI) = 0.96–1.14); glioma (OR = 0.51, 95% CI, 0.43–0.59); neuroblastoma (OR = 0.46, 95% CI, 0.39–0.55)] in comparison to the children of US-born Hispanic women [ALL (OR = 1.23, 95% CI, 1.11–1.37); glioma (OR = 0.75, 95% CI, 0.62–0.90); neuroblastoma (OR = 0.63, 95% CI, 0.51–0.78); referent group was the children of US-born Whites]. The odds for rhabdomyosarcoma and acute myeloid leukemia were equivalent between Hispanics regardless of maternal place of birth. Hepatoblastoma was higher among the children of foreign-born mothers (OR = 1.35, 95% CI, 0.87–2.10) than those of US-born Hispanic mothers (OR = 0.93, 95% CI, 0.56–1.55) while bone tumors were higher among the children of US-born mothers (OR = 2.08, 95% CI, 1.11–3.88) compared to the children of foreign-born mothers (OR = 0.73, 95% CI, 0.38–1.41). Conclusions: With notable exceptions, the children of foreign-born Hispanic mothers tended to have cancer rates lower than those of US-born Hispanic mothers. Risk factors identified as driving the Hispanic paradox may be fruitful for study among these childhood cancer types.
Are Women Willing to Change Breast Cancer Screening Guidelines?
Authors: Cohn W , Novicoff W , Dean McKinney M , Guterbock T , Rexrode D , Eggleston C , Harvey J , Knaus W
Published: April 2015

This purpose of this study is to evaluate the willingness of women to change their breast cancer screening practices if given personalized recommendations based on risk factors such as breast density, family history and lifestyle. Methods: A random sample of 1,024 Virginia women between age 35–70 years and without breast cancer, reached by landline and cell phone, completed a 24-minute interview. Results: Just over half (54.6%) of women are definitely or probably willing to reduce their frequency of breast cancer screening if provided with personalized recommendations. This compares to 81.9% who are definitely or probably willing to increase screening. The most cited disadvantage for reduced screening was delayed detection of breast cancer (77%) while the most cited advantage for increased screening is earlier detection (82%). Women are willing to change their type of screening (92.3%). Women who were more likely to be willing to reduce screening are those with a lower perceived risk of breast cancer, less familiarity with risk factors and recommendations. When asked what they needed to know to make a change, women cited advice of a doctor (52.1%), research/evidence (38.9%) and comparison with old recommendations (22.5%) most frequently. Advice of a radiologist was only stated by 2.3% of the women. Conclusions: These results suggest that most women will be willing to change their breast cancer screening frequency especially if recommended by their primary care physician. Women do not view their radiologist as having a primary role in delivering screening recommendations; this underscores the need to educate primary healthcare providers regarding breast screening recommendations.
Pharmacological and Protein Profiling Suggests Venetoclax (ABT-199) as Optimal Partner with Ibrutinib in Chronic Lymphocytic Leukemia
Authors: Cervantes-Gomez Fabiola , Lamothe Betty , Woyach Jennifer A. , Wierda William G. , Keating Michael J. , Balakrishnan Kumudha , Gandhi Varsha
Published: April 2015

Purpose: Bruton's tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain. Though ibrutinib results in impressive clinical activity in chronic lymphocytic leukemia (CLL), most patients achieve only partial remission due to residual disease. We performed a pharmacologic profiling of residual circulating CLL cells from patients receiving ibrutinib to identify optimal agents that could induce cell death of these lymphocytes.

Experimental Design: Ex vivo serial samples of CLL cells from patients on ibrutinib were obtained prior and after (weeks 2, 4, and 12) the start of treatment. These cells were incubated with PI3K inhibitors (idelalisib or IPI-145), bendamustine, additional ibrutinib, or BCL-2 antagonists (ABT-737 or ABT-199), and cell death was measured. In vitro investigations complemented ex vivo studies. Immunoblots for BTK signaling pathway and antiapoptotic proteins were performed.

Results: The BCL-2 antagonists, especially ABT-199, induced high cell death during ex vivo incubations. In concert with the ex vivo data, in vitro combinations also resulted in high cytotoxicity. Serial samples of CLL cells obtained before and 2, 4, 12, or 36 weeks after the start of ibrutinib showed inhibition of BTK activity and sensitivity to ABTs. Among the three BCL-2 family antiapoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2.

Conclusions: Our biologic and molecular results suggest that ibrutinib and ABT-199 combination should be tested clinically against CLL. Clin Cancer Res; 21(16); 3705–15. ©2015 AACR.
Diffuse Large B-cell Lymphoma Classification Tied Up Nicely with a “String”
Authors: Rimsza Lisa M.
Published: April 2015

Molecular classification of diffuse large B-cell lymphoma (DLBCL) is a critical biologic, prognostic, and predictive distinction. Since the discovery of two molecular types of DLBCL in otherwise morphologically indistinguishable cases, numerous methodologies for making this distinction have been published. A method and technical platform may now be reaching consensus. Clin Cancer Res; 21(10); 2204–6. ©2015 AACR.

See related article by Veldman-Jones et al., p. 2367
Efficacy of Carboplatin Alone and in Combination with ABT888 in Intracranial Murine Models of BRCA-Mutated and BRCA–Wild-Type Triple-Negative Breast Cancer
Authors: Karginova Olga , Siegel Marni B. , Van Swearingen Amanda E.D. , Deal Allison M. , Adamo Barbara , Sambade Maria J. , Bazyar Soha , Nikolaishvili-Feinberg Nana , Bash Ryan , O'Neal Sara , Sandison Katie , Parker Joel S. , Santos Charlene , Darr David , Zamboni William , Lee Yueh Z. , Miller C. Ryan , Anders Carey K.
Published: April 2015

Patients with breast cancer brain metastases have extremely limited survival and no approved systemic therapeutics. Triple-negative breast cancer (TNBC) commonly metastasizes to the brain and predicts poor prognosis. TNBC frequently harbors BRCA mutations translating to platinum sensitivity potentially augmented by additional suppression of DNA repair mechanisms through PARP inhibition. We evaluated brain penetrance and efficacy of carboplatin ± the PARP inhibitor ABT888, and investigated gene-expression changes in murine intracranial TNBC models stratified by BRCA and molecular subtype status. Athymic mice were inoculated intracerebrally with BRCA-mutant: SUM149 (basal), MDA-MB-436 (claudin-low); or BRCA–wild-type (wt): MDA-MB-468 (basal), MDA-MB-231BR (claudin-low). TNBC cells were treated with PBS control [intraperitoneal (IP), weekly], carboplatin (50 mg/kg/wk, IP), ABT888 (25 mg/kg/d, oral gavage), or their combination. DNA damage (γ-H2AX), apoptosis (cleaved caspase-3, cC3), and gene expression were measured in intracranial tumors. Carboplatin ± ABT888 significantly improved survival in BRCA-mutant intracranial models compared with control, but did not improve survival in BRCA-wt intracranial models. Carboplatin + ABT888 revealed a modest survival advantage versus carboplatin in BRCA-mutant models. ABT888 yielded a marginal survival benefit in the MDA-MB-436, but not in the SUM149 model. BRCA-mutant SUM149 expression of γ-H2AX and cC3 proteins was elevated in all treatment groups compared with control, whereas BRCA-wt MDA-MB-468 cC3 expression did not increase with treatment. Carboplatin treatment induced common gene-expression changes in BRCA-mutant models. Carboplatin ± ABT888 penetrates the brain and improves survival in BRCA-mutant intracranial TNBC models with corresponding DNA damage and gene-expression changes. Combination therapy represents a potential promising treatment strategy for patients with TNBC brain metastases warranting further clinical investigation. Mol Cancer Ther; 14(4); 920–30. ©2015 AACR.
Loss of miR-223 and JNK Signaling Contribute to Elevated Stathmin in Malignant Pleural Mesothelioma
Authors: Birnie Kimberly A. , Yip Yan Y. , Ng Dominic C.H. , Kirschner Michaela B. , Reid Glen , Prêle Cecilia M. , Musk Arthur W. (Bill) , Lee Y.C. Gary , Thompson Philip J. , Mutsaers Steven E. , Badrian Bahareh
Published: April 2015

Malignant pleural mesothelioma (MPM) is often fatal, and studies have revealed that aberrant miRNAs contribute to MPM development and aggressiveness. Here, a screen of miRNAs identified reduced levels of miR-223 in MPM patient specimens. Interestingly, miR-223 targets Stathmin (STMN1), a microtubule regulator that has been associated with MPM. However, whether miR-223 regulates STMN1 in MPM and the functions of miR-223 and STMN1 in this disease are yet to be determined. STMN1 is also regulated by c-Jun N-terminal kinase (JNK) signaling, but whether this occurs in MPM and whether miR-223 plays a role are unknown. The relationship between STMN1, miR-223, and JNK was assessed using MPM cell lines, cells from pleural effusions, and MPM tissue. Evidence indicates that miR-223 is decreased in all MPM tissue compared with normal/healthy tissue. Conversely, STMN1 expression was higher in MPM cell lines when compared with primary mesothelial cell controls. Following overexpression of miR-223 in MPM cell lines, STMN1 levels were reduced, cell motility was inhibited, and tubulin acetylation induced. Knockdown of STMN1 using siRNAs led to inhibition of MPM cell proliferation and motility. Finally, miR-223 levels increased while STMN1 was reduced following the re-expression of the JNK isoforms in JNK-null murine embryonic fibroblasts, and STMN1 was reduced in MPM cell lines following the activation of JNK signaling.

Implications: miR-223 regulates STMN1 in MPM, and both are in turn regulated by the JNK signaling pathway. As such, miR-223 and STMN1 play an important role in regulating MPM cell motility and may be therapeutic targets. Mol Cancer Res; 13(7); 1106–18. ©2015 AACR.
MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2
Authors: Nowak Dawid G. , Cho Hyejin , Herzka Tali , Watrud Kaitlin , DeMarco Daniel V. , Wang Victoria M.Y. , Senturk Serif , Fellmann Christof , Ding David , Beinortas Tumas , Kleinman David , Chen Muhan , Sordella Raffaella , Wilkinson John E. , Castillo-Martin Mireia , Cordon-Cardo Carlos , Robinson Brian D. , Trotman Lloyd C.
Published: April 2015

We have recently recapitulated metastasis of human PTEN/TP53–mutant prostate cancer in the mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by MYC, and not AKT, activation. Here, we show that cell–cell communication by IL6 drives the AKT–MYC switch through activation of the AKT-suppressing phosphatase PHLPP2, when PTEN and p53 are lost together, but not separately. IL6 then communicates a downstream program of STAT3-mediated MYC activation, which drives cell proliferation. Similarly, in tissues, peak proliferation in Pten/Trp53–mutant primary and metastatic prostate cancer does not correlate with activated AKT, but with STAT3/MYC activation instead. Mechanistically, MYC strongly activates the AKT phosphatase PHLPP2 in primary cells and prostate cancer metastasis. We show genetically that Phlpp2 is essential for dictating the proliferation of MYC-mediated AKT suppression. Collectively, our data reveal competition between two proto-oncogenes, MYC and AKT, which ensnarls the Phlpp2 gene to facilitate MYC-driven prostate cancer metastasis after loss of Pten and Trp53.

Significance: Our data identify IL6 detection as a potential causal biomarker for MYC-driven metastasis after loss of PTEN and p53. Second, our finding that MYC then must supersede AKT to drive cell proliferation points to MYC inhibition as a critical part of PI3K pathway therapy in lethal prostate cancer. Cancer Discov; 5(6); 636–51. ©2015 AACR.

This article is highlighted in the In This Issue feature, p. 565