bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiprogram Throughput Metrics
Authors: Eyerman Stijn , Michaud Pierre , Rogiest Wouter
Published: October 2014

Running multiple programs on a processor aims at increasing the throughput of that processor. However, defining meaningful throughput metrics in a simulation environment is not as straightforward as reporting execution time. This has led to an ongoing debate on what forms a meaningful throughput metric for multiprogram workloads. We present a method to construct throughput metrics in a systematic way: we start by expressing assumptions on job size, job distribution, scheduling, and so forth that together define a theoretical throughput experiment. The throughput metric is then the average throughput of this experiment. Different assumptions lead to different metrics, so one should be aware of these assumptions when making conclusions based on results using a specific metric.

Throughput metrics should always be defined from explicit assumptions, because this leads to a better understanding of the implications and limits of the results obtained with that metric. We elaborate multiple metrics based on different assumptions. In particular, we identify the assumptions that lead to the commonly used weighted speedup and harmonic mean of speedups. Our study clarifies that they are actual throughput metrics, which was recently questioned. We also propose some new throughput metrics, which cannot always be expressed as a closed formula. We use real experimental data to characterize metrics and show how they relate to each other.
Influence of Search Neutrality on the Economics of Advertisement-Financed Content
Authors: Coucheney Pierre , D'acquisto Giuseppe , Maillé Patrick , Naldi Maurizio , Tuffin Bruno
Published: October 2014

The search neutrality debate questions the ranking methods of search engines. We analyze the issue when content providers offer content for free, but get revenues from advertising. We investigate the noncooperative game among competing content providers under different ranking policies. When the search engine is not involved with high-quality content providers, it should adopt neutral ranking, also maximizing user quality-of-experience. If the search engine controls high-quality content, favoring its ranking and adding advertisement yield a larger revenue. Though user perceived quality may not be impaired, the advertising revenues of the other content providers drastically decrease.
Regulation of Off-Network Pricing in a Nonneutral Network
Authors: Altman Eitan , Hanawal Manjesh Kumar , Sundaresan Rajesh
Published: October 2014

Representatives of several Internet service providers (ISPs) have expressed their wish to see a substantial change in the pricing policies of the Internet. In particular, they would like to see content providers (CPs) pay for use of the network, given the large amount of resources they use. This would be in clear violation of the “network neutrality” principle that had characterized the development of the wireline Internet. Our first goal in this article is to propose and study possible ways of implementing such payments and of regulating their amount. We introduce a model that includes the users' behavior, the utilities of the ISP and of the CPs, and, the monetary flow that involves the content users, the ISP and CP, and, in particular, the CP's revenues from advertisements. We consider various game models and study the resulting equilibria; they are all combinations of a noncooperative game (in which the ISPs and CPs determine how much they will charge the users) with a “cooperative” one on how the CP and the ISP share the payments. We include in our model a possible asymmetric weighting parameter (that varies between zero to one). We also study equilibria that arise when one of the CPs colludes with the ISP. We also study two dynamic game models as well as the convergence of prices to the equilibrium values.
Understanding Quota Dynamics in Wireless Networks
Authors: Andrews Matthew , Bruns Glenn , Doğru Mustafa , Lee Hyoseop
Published: October 2014

In designing new service plans, network service providers need to understand how consumption of voice or data service will change in response to pricing signals. It is difficult to acquire such information from customer usage data because voice minutes and data bandwidth are typically sold in the form of large quotas. We address this issue by studying how end-users consume their quotas, both in a prepaid setting (where users pay in advance and refill as needed) and a postpaid setting (where users pay each month for a fixed amount of quota). Our presentation has three main parts. In the first we present data on quota usage for prepaid voice/text services and show that users reduce their voice usage when their balances become low. Moreover, when balances are low there is a tendency to shift from voice to SMS. In the second part, we provide descriptive models of both prepaid and postpaid services. The main feature of these models is that there is a background level of potential demand and the rate at which this potential demand is realized depends on the amount of quota balance available. In the third part, we propose utility maximizing models that can account for this type of behavior. In the prepaid case the main feature of the model is a discount function that represents the perceived cost to the user of a quota refill that will occur sometime in the future. In the postpaid case, where the end-user is attempting to get the maximum amount of utility from his monthly quota, we present a dynamic programming formulation in which utility functions are time varying and not known to the user in advance.
Cause Lawyering
Authors: Marshall Anna-Maria , Hale Daniel Crocker
Published: November 2014

Cause lawyers are powerful gatekeepers to the political and legal institutions where the dynamics between law and social change get played out. Yet, after years of research, we still seem far from a settled picture of cause lawyering and cause lawyers. In this article, we first describe the social and cultural practices that constitute cause lawyering. Second, we link cause lawyering to the clients served—from sophisticated social movement organizations to ordinary people. We show that cause lawyering is powerfully shaped by the clients served and by the contexts in which that lawyer–client relationship is situated. Finally, we examine the political context of cause lawyering. We also address larger questions in this research tradition: Is cause lawyering different from other forms of lawyering? How and why does cause lawyering produce tension between the lawyers and their clients? Does cause lawyering generate different kinds of professional and political identities?
Foliar Sprays of Citric Acid and Malic Acid Modify Growth, Flowering, and Root to Shoot Ratio ofGazania(Gazania rigensL.): A Comparative Analysis by ANOVA and Structural Equations Modeling
Authors: Talebi Majid , Hadavi Ebrahim , Jaafari Nima
Published: October 2014

Foliar application of two levels of citric acid and malic acid (100 or 300 mg L−1) was investigated on flower stem height, plant height, flower performance and yield indices (fresh yield, dry yield and root to shoot ratio) ofGazania. Distilled water was applied as control treatment. Multivariate analysis revealed that while the experimental treatments had no significant effect on fresh weight and the flower count, the plant dry weight was significantly increased by 300 mg L−1malic acid. Citric acid at 100 and 300 mg L−1and 300 mg L−1malic acid increased the root fresh weight significantly. Both the plant height and peduncle length were significantly increased in all applied levels of citric acid and malic acid. The display time of flowers on the plant increased in all treatments compared to control treatment. The root to shoot ratio was increased significantly in 300 mg L−1citric acid compared to all other treatments. These findings confirm earlier reports that citric acid and malic acid as environmentally sound chemicals are effective on various aspects of growth and development of crops. Structural equations modeling is used in parallel to ANOVA to conclude the factor effects and the possible path of effects.
Functional Polymorphisms of Matrix Metalloproteinases 1 and 9 Genes in Women with Spontaneous Preterm Birth
Authors: Pereza Nina , Pleša Ivana , Peterlin Ana , Jan Žiga , Tul Nataša , Kapović Miljenko , Ostojić Saša , Peterlin Borut
Published: October 2014

Objective. The aim of this study was to investigate the association of functionalMMP-1-1607 1G/2G andMMP-9-1562 C/T gene polymorphisms with spontaneous preterm birth (SPTB; preterm birth with intact membranes) in European Caucasian women, as well as the contribution of these polymorphisms to different clinical features of women with SPTB.Methods and Patients. A case-control study was conducted in 113 women with SPTB and 119 women with term delivery (control group). Genotyping ofMMP-1-1607 1G/2G andMMP-9-1562 C/T gene polymorphisms was performed using the combination of polymerase chain reaction and restriction fragment length polymorphism methods.Results. There were no statistically significant differences in the distribution of neither individual nor combinations of genotype and allele frequencies ofMMP-1-1607 1G/2G andMMP-9-1562 C/T polymorphisms between women with SPTB and control women. Additionally, these polymorphisms do not contribute to any of the clinical characteristics of women with SPTB, including positive and negative family history of SPTB, gestational age at delivery, and maternal age at delivery, nor fetal birth weight.Conclusion. We did not find the evidence to support the association ofMMP-1-1607 1G/2G andMMP-9-1562 C/T gene polymorphisms with SPTB in European Caucasian women.
Proatherogenic Oxidized Low-Density Lipoprotein/β2-Glycoprotein I Complexes in Arterial and Venous Disease
Authors: Berger Jeffrey S. , Rockman Caron B. , Guyer Kirk E. , Lopez Luis R.
Published: October 2014

OxLDL/β2GPI complexes have been implicated in the initiation and progression of atherosclerosis and associated with disease severity and adverse outcomes. We investigate the significance of anti-oxLDL/β2GPI antibodies and oxLDL/β2GPI complexes in patients with arterial and idiopathic venous disease. A cohort of 61 arterial disease patients, 32 idiopathic venous disease patients, and 53 healthy controls was studied. Because statins influence oxLDL/β2GPI, these complexes were analyzed on subjects not taking statins. Arterial and venous groups expressed higher levels of IgG anti-oxLDL/β2GPI antibodies than controls without any other significant clinical association. OxLDL/β2GPI complexes were significantly elevated in arterial (0.69 U/mL,P=0.004) and venous disease (0.54 U/mL,P=0.025) than controls (0.39 U/mL). Among arterial diseases, oxLDL/β2GPI was 0.85 U/mL for carotid artery disease, 0.72 U/mL for peripheral artery disease, and 0.52 U/mL for abdominal aortic aneurysm. There was a significant association with male gender, age, hypertension, and history of thrombosis. Subjects with oxLDL/β2GPI above the median (0.25 U/mL) were more likely to have arterial (OR 4.5,P=0.004) or venous disease (OR 4.1,P=0.008). Multivariate regression indicated that males (P=0.021), high cholesterol (P=0.011), and carotid disease (P=0.023) were significant predictors of oxLDL/β2GPI. The coexistence of oxLDL/β2GPI in arterial and venous disease may suggest a common oxidative mechanism that independently predicts carotid artery disease.
Experiences of Dental Care and Dental Anxiety in Adults with Autism Spectrum Disorder
Authors: Blomqvist My , Dahllöf Göran , Bejerot Susanne
Published: October 2014

Dental anxiety is associated with previous distressing dental experiences, such as lack of understanding of the dentist intentions, perceptions of uncontrollability and experiences of pain during dental treatment. People with autism spectrum disorder (ASD) are impaired in building flexible predictions and expectations, which is very much needed during a dental visit. The aims of the study were to investigate if people with ASD have more negative dental experiences and a higher level of dental anxiety compared to a matched control group. Forty-seven adults with ASD and of normal intellectual performance, and 69 age- and sex-matched typically developing controls completed questionnaires on previous dental experiences and dental anxiety, the Dental Anxiety Scale, and the Dental Beliefs Survey. The ASD group experienced pain during dental treatments more often than the controls and 22% had repeatedly experienced being forced to dental treatment they were not prepared for, compared to 3% of the controls. A higher level of dental anxiety was reported by the ASD group. Dental treatment and methods for supporting the communication with patients with ASD need to be developed, in order to reduce the negative dental experiences and dental anxiety in people with ASD.
Preservation of Involved Teeth Associated with Large Dentigerous Cysts
Authors: Guven Yeliz , Kasimoglu Yelda , Soluk Tekkesin Merva , Ulug Dicle , Cankaya Abdulkadir Burak , Tuna Elif Bahar , Gencay Koray , Aktoren Oya
Published: October 2014

Dentigerous cysts (DCs) are benign odontogenic cysts that are associated with the crowns of permanent teeth. The purpose of this study is to describe the management of DCs in four children. Four boys aged between 7 and 9 years were referred to our clinics with the complaints of intraoral alveolar swelling or facial asymmetry on the affected area. The panoramic radiographies showed large, well-defined radiolucent lesions associated with the deciduous teeth and displaced tooth buds. The treatment consisted of the extraction of the involved deciduous tooth and marsupialization of the cyst to allow eruption of the permanent tooth. Permanent teeth displaced by the DCs in three cases erupted spontaneously within one-year period. The case with horizontally displaced permanent tooth was managed by replantation. This is the first time that underlying permanent tooth in a DC case was intentionally replanted.
Effects of a Multidisciplinary Educational Rehabilitative Intervention in Breast Cancer Survivors: The Role of Body Image on Quality of Life Outcomes
Authors: Morone Giovanni , Iosa Marco , Fusco Augusto , Scappaticci Antonella , Alcuri Maria Rosaria , Saraceni Vincenzo Maria , Paolucci Stefano , Paolucci Teresa
Published: October 2014

In breast cancer survivors, own body image may change due to physical and psychological reasons, worsening women’s living. The aim of the study was to investigate whether body image may affect the functional and quality of life outcomes after a multidisciplinary and educational rehabilitative intervention in sixty women with primary nonmetastatic breast cancer who have undergone conservative surgery. To assess the quality of life was administered The European Organization for Research and Treatment of Cancer Study Group on Quality of Life core questionnaire, while to investigate the psychological features and self-image were administered the following scales: the Body Image Scale, the Hamilton Rating Scale for Depression, and the State-Trait Anxiety Inventory. To assess the recovery of the function of the shoulder were administered: the Disabilities of the Arm, Shoulder, and Hand Questionnaire and the Constant-Murley Score. Data were collected at the baseline, at the end of the intervention, and at 3-month follow-up. We found a general improvement in the outcomes related to quality of life, and physical and psychological features after treatment (P< 0.001). During follow-up period, a higher further improvement in women without alterations in body image in respect of those with an altered self-perception of their own body was found (P= 0.01). In conclusion, the body image may influence the efficacy of a rehabilitative intervention, especially in the short term of follow-up.
Study of the Antibacterial Efficacy of Bainiku-Ekisu against Pathogens
Authors: Yang Deng-Jye , Chen Hsin-Yi , Liu Shih-Chuan
Published: October 2014

The research was undertaken to determine the bacteriostatic effects of the concentrate of Japanese apricot juice (bainiku-ekisu), which is a popular health food in Taiwan and Japan, on Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, and Escherichia coli ATCC 25922. The results show that E. faecalis, S. aureus, and E. coli could be killed or inhibited by bainiku-ekisu at concentrations between 1.0 and 10.0 mg/mL. The minimum inhibitory concentration (MIC) was 1 mg/mL for all strains, and the minimum bactericidal concentrations (MBCs) were 5, 2.5, and 2.5 mg/mL for E. faecalis, S. aureus, and E. coli, respectively. Using the growth rate to calculate the MICs and MBCs, the MICs were 1.55, 1.43, and 0.97 mg/mL, and the MBCs were 2.59, 2.63, and 2.25 mg/mL for E. faecalis, S. aureus, and E. coli, respectively. According to the D values, E. faecalis and S. aureus exhibited lower resistance than E. coli at lower bainiku-ekisu concentrations (1.0 and 2.5 mg/mL), and the resistance of these two pathogens was better than that of E. coli at higher bainiku-ekisu concentrations (5.0 and 10.0 mg/mL). The Z values of the E. faecalis, S. aureus, and E. coli strains were 3.47, 4.93, and 11.62 mg/mL, respectively.
Disparities in Health Outcomes of Return Migrants in Mexico
Authors: Wilson Fernando A. , Stimpson Jim P. , Pagán José A.
Published: October 2014

Objective. The epidemiological paradox posits that immigrants in USA experience better health outcomes than nonimmigrants with similar socioeconomic status. However, little is known about the development of health problems over the life course for immigrants who return to their country of origin.Methods. The Mexican Migration Project provides detailed information on immigration, health, and socioeconomic status for 671 unauthorized migrants, 101 legal migrants, and 3,748 nonmigrants. Cox regression estimated the adjusted hazard of developing hypertension, diabetes/prediabetes, poor mental health, and heart and lung problems.Results. Legal immigrants to USA did not have a significantly higher risk of having a self-reported diagnosis of hypertension, diabetes, heart or lung problems, or poor mental health compared to nonmigrants. However, the hazard ratio for unauthorized deported immigrants ranged from 2.25 (CI: 1.29–3.93) for diabetes to 4.43 (CI: 2.33–8.40) for poor mental health compared to nonmigrants.Conclusions. Health problems occur several years earlier among unauthorized immigrants compared to individuals who never migrated. Poor access to healthcare services combined with USA lifestyle and working conditions after migration to the USA may contribute to an increased risk for the development of chronic health conditions later in life.
Application of Design of Experiment for Polyox and Xanthan Gum Coated Floating Pulsatile Delivery of Sumatriptan Succinate in Migraine Treatment
Authors: Jagdale Swati C. , Pawar Chandrakala R.
Published: October 2014

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR205 and xanthan gum. 32experimental design was applied. Optimized formulation was evaluated for physical characteristics andin-vitroandin-vivostudy. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed byin-vivoX-ray study.
How to Motivate Whole Blood Donors to Become Plasma Donors
Authors: Godin Gaston , Germain Marc
Published: October 2014

This study tested the efficacy of interventions to recruit new plasma donors among whole blood donors. A sample of 924 donors was randomized to one of three conditions: control; information only by nurse; and information plus self-positive image message by nurse (SPI). Participants in the control condition only received a leaflet describing the plasma donation procedure. In the two experimental conditions the leaflet was explained face-to-face by a nurse. The dependent variables were the proportion of new plasma donors and the number of donations at six months. Overall, 141 (15.3%) new plasma donors were recruited at six months. There were higher proportions of new plasma donors in the two experimental conditions compared to the control condition (P<.001); the two experimental conditions did not differ. Also, compared to the control condition, those in the experimental conditions (all Ps<.001) gave plasma more often (information only by nurse:  d=.26; SPI: d=.32); the SPI intervention significantly outperformed (P<.05) the information only by nurse condition. The results suggest that references to feelings of SPI such as feeling good and being proud and that giving plasma is a rewarding personal experience favor a higher frequency of plasma donation.
Analysis of a Compact and Superdirective Metamaterial-Inspired Monopole Antenna
Authors: Dakhli Saber , Rmili Hatem , Mahdjoubi Kourosh , Floc’h Jean-Marie , Choubani Fethi
Published: October 2014

The directivity of a metamaterial-inspired compact (0.145λ0) monopole antenna was investigated. The proposed structure is composed of a split-ring resonator (SRR) parasitic element placed in the vicinity of a monopole antenna. Two configurations denoted by A1 and A2 were considered depending on the position of the slot in the SRR element. By analyzing simulated and measured results, the superdirectivity (7.5 dBi for A1 and 9 dBi for A2) of the structure was discussed. It is found that the monopole-SRR and/or ground plane-SRR coupling effects may be responsible for the superdirectivity of the structure.
Strong Convergence of Modified Algorithms Based on the Regularization for the Constrained Convex Minimization Problem
Authors: Tian Ming , Gong Jun-Ying
Published: October 2014

As is known, the regularization method plays an important role in solving constrained convex minimization problems. Based on the idea of regularization, implicit and explicit iterative algorithms are proposed in this paper and the sequences generated by the algorithms can converge strongly to a solution of the constrained convex minimization problem, which also solves a certain variational inequality. As an application, we also apply the algorithm to solve the split feasibility problem.
Balanced Centrality of Networks
Authors: Debono Mark , Lauri Josef , Sciriha Irene
Published: November 2014

There is an age-old question in all branches of network analysis. What makes an actor in a
network important, courted, or sought? Both Crossley and Bonacich contend that rather than
its intrinsic wealth or value, an actor’s status lies in the structures of its interactions with other
actors. Since pairwise relation data in a network can be stored in a two-dimensional array or
matrix, graph theory and linear algebra lend themselves as great tools to gauge the centrality
(interpreted as importance, power, or popularity, depending on the purpose of the network) of
each actor. We express known and new centralities in terms of only two matrices associated with
the network. We show that derivations of these expressions can be handled exclusively through
the main eigenvectors (not orthogonal to the all-one vector) associated with the adjacency
matrix. We also propose a centrality vector (SWIPD) which is a linear combination of the
square, walk, power, and degree centrality vectors with weightings of the various centralities
depending on the purpose of the network. By comparing actors’ scores for various weightings,
a clear understanding of which actors are most central is obtained. Moreover, for threshold
networks, the (SWIPD) measure turns out to be independent of the weightings.
The Effect of Ultrafine Magnesium Hydroxide on the Tensile Properties and Flame Retardancy of Wood Plastic Composites
Authors: Wu Zhiping , Hu Na , Wu Yiqiang , Wu Shuyun , Qin Zu
Published: October 2014

The effect of ultrafine magnesium hydroxide (UMH) and ordinary magnesium hydroxide (OMH) on the tensile properties and flame retardancy of wood plastic composites (WPC) were investigated by tensile test, oxygen index tester, cone calorimeter test, and thermogravimetric analysis. The results showed that ultrafine magnesium hydroxide possesses strengthening and toughening effect of WPC. Scanning electron micrograph (SEM) of fracture section of samples provided the positive evidence that the tensile properties of UMH/WPC are superior to that of WPC and OMH/WPC. The limited oxygen index (LOI) and cone calorimeter test illustrated that ultrafine magnesium hydroxide has stronger flame retardancy and smoke suppression effect of WPC compared to that of ordinary magnesium hydroxide. The results of thermogravimetric analysis implied that ultrafine magnesium hydroxide can improve the char structure which plays an important role in reducing the degradation speed of the inner matrix during combustion process and increases the char residue at high temperature.
Disaggregated Data and Beyond: Future Queries in Cancer Control Research
Authors: Nguyen Anh Bao , Chawla Neetu , Noone Anne-Michelle , Srinivasan Shobha
Published: November 2014

The goal of health equity requires the collection and reporting of disaggregated data in underrepresented populations such as Asian American (AA) and Native Hawaiian and Other Pacific Islander (NHOPI) communities. A recent Department of Health and Human Services report outlines the necessity for disaggregated data, which would offer communities, providers, and planners better tools to address health problems. In a recent collaboration, the National Cancer Institute (NCI) and several registries published a series of articles tracking cancer incidence data on AA and NHOPI communities using data from the NCI's Surveillance, Epidemiology, and End Results (SEER) program. The findings indicate a need for concentrated focus and planning for the next stages of cancer prevention and control for AA and NHOPI subpopulations. In this article, we provide (i) the context for the perpetuation of the model minority myth as well as historical and sociocultural factors that have shaped health and disease for AA and NHOPI subgroups; (ii) potential strategies for research and public health policy for AA and NHOPI groups using subpopulation-based approaches while addressing challenges and limitations; and (iii) a portfolio analysis of currently funded projects within the NCI/DCCPS to identify gaps and areas of potential research.

See all the articles in this CEBP Focus section, “Cancer in Asian and Pacific Islander Populations.”

Cancer Epidemiol Biomarkers Prev; 23(11); 2266–72. ©2014 AACR.
Cancer In Silico Drug Discovery: A Systems Biology Tool for Identifying Candidate Drugs to Target Specific Molecular Tumor Subtypes
Authors: San Lucas F. Anthony , Fowler Jerry , Chang Kyle , Kopetz Scott , Vilar Eduardo , Scheet Paul
Published: October 2014

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. Mol Cancer Ther; 13(12); 3230–40. ©2014 AACR.
HIF1α Regulates mTOR Signaling and Viability of Prostate Cancer Stem Cells
Authors: Marhold Maximilian , Tomasich Erwin , El-Gazzar Ahmed , Heller Gerwin , Spittler Andreas , Horvat Reinhard , Krainer Michael , Horak Peter
Published: October 2014

Tumor-initiating subpopulations of cancer cells, also known as cancer stem cells (CSC), were recently identified and characterized in prostate cancer. A well-characterized murine model of prostate cancer was used to investigate the regulation of hypoxia-inducible factor 1α (HIF1A/HIF1α) in CSCs and a basal stem cell subpopulation (Lin−/Sca-1+/CD49f+) was identified, in primary prostate tumors of mice, with elevated HIF1α expression. To further analyze the consequences of hypoxic upregulation on stem cell proliferation and HIF1α signaling, CSC subpopulations from murine TRAMP-C1 cells (Sca-1+/CD49f+) as well as from a human prostate cancer cell line (CD44+/CD49f+) were isolated and characterized. HIF1α levels and HIF target gene expression were elevated in hypoxic CSC-like cells, and upregulation of AKT occurred through a mechanism involving an mTOR/S6K/IRS-1 feedback loop. Interestingly, resistance of prostate CSCs to selective mTOR inhibitors was observed because of HIF1α upregulation. Thus, prostate CSCs show a hypoxic deactivation of a feedback inhibition of AKT signaling through IRS-1. In light of these results, we propose that deregulation of the PI3K/AKT/mTOR pathway through HIF1α is critical for CSC quiescence and maintenance by attenuating CSC metabolism and growth via mTOR and promoting survival by AKT signaling. We also propose that prostate CSCs can exhibit primary drug resistance to selective mTOR inhibitors.

Implications: This work contributes to a deeper understanding of hypoxic regulatory mechanisms in CSCs and will help devise novel therapies against prostate cancer. Mol Cancer Res; 13(3); 556–64. ©2014 AACR.
A Novel Preclinical Method to Quantitatively Evaluate Early-Stage Metastatic Events at the Murine Blood–Brain Barrier
Authors: Adkins Chris E. , Nounou Mohamed I. , Mittapalli Rajendar K. , Terrell-Hall Tori B. , Mohammad Afroz S. , Jagannathan Rajaganapathi , Lockman Paul R.
Published: October 2014

The observation that approximately 15% of women with disseminated breast cancer will develop symptomatic brain metastases combined with treatment guidelines discouraging single-agent chemotherapeutic strategies facilitates the desire for novel strategies aimed at outright brain metastasis prevention. Effective and robust preclinical methods to evaluate early-stage metastatic processes, brain metastases burden, and overall mean survival are lacking. Here, we develop a novel method to quantitate early metastatic events (arresting and extravasation) in addition to traditional end time-point parameters such as tumor burden and survival in an experimental mouse model of brain metastases of breast cancer. Using this method, a reduced number of viable brain-seeking metastatic cells (from 3,331 ± 263 cells/brain to 1,079 ± 495 cells/brain) were arrested in brain one week postinjection after TGFβ knockdown. Treatment with a TGFβ receptor inhibitor, galunisertib, reduced the number of arrested cells in brain to 808 ± 82 cells/brain. Furthermore, we observed a reduction in the percentage of extravasated cells (from 63% to 30%) compared with cells remaining intralumenal when TGFβ is knocked down or inhibited with galunisertib (40%). The observed reduction of extravasated metastatic cells in brain translated to smaller and fewer brain metastases and resulted in prolonged mean survival (from 36 days to 62 days). This method opens up potentially new avenues of metastases prevention research by providing critical data important to early brain metastasis of breast cancer events. Cancer Prev Res; 8(1); 68–76. ©2014 AACR.
Application of Three Focused Cluster Detection Methods to Study Geographic Variation in the Incidence of Multiple Sclerosis in Manitoba, Canada
Authors: Torabi Mahmoud , Green Chris , Yu Nancy , Marrie Ruth Ann
Published: October 2014

Background: Macroscopic geographic variation in the incidence and prevalence of MS is well-recognized. Microscopic geographic variation in the distribution of MS is also recognized, but less well-studied. Most studies have focused on prevalent cases of MS, although studies of variation in disease incidence are more relevant for developing etiologic hypotheses. We aimed to study geographic variation in the incidence of MS using three different methods. Methods: We used population-based administrative (health claims) data to identify 2,290 incident cases of MS in the province of Manitoba, Canada from 1990 to 2006. We applied three focused cluster-detection procedures, including the circular spatial scan statistic (CSS), flexible spatial scan statistic (FSS), and Bayesian disease mapping (BYM), to the dataset. Results: The CSS and FSS methods identified 30 and 26 regions as potential clusters, respectively, although the regions identified differed slightly due to the non-circular shape of some regions in Manitoba. The BYM approach identified 37 regions as potential clusters, again with some differences as compared to the other two methods. Twelve regions were identified as potential clusters by all three methods. All methods identified the western part of the city of Winnipeg as a significant cluster. Using the BYM approach, the incidence of MS was highest among areas of higher socioeconomic status. Conclusions: Two methods CSS and FSS only capture geographical variations and are not able to control for confounders at the same time which may lead to mis-identification of clusters. However, the BYM method can simultaneously identify geographical variations and control for possible confounders.
Post-Thrombolysis Hemorrhage Risk of Unruptured Intracranial Aneurysms
Authors: Chen Fujian , Yan Shenqiang , Jin Xinchun , Lin Chen , Cao Jin
Published: November 2014

Background/Aims: It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. Methods: We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. Results: We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I2 = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I2 = 28.1%). Conclusion: Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH. i 2014 S. Karger AG, Basel
Gender and Sex Manifestations in Hysteria Across Medicine and the Arts
Authors: Dmytriw Adam A.
Published: November 2014

The diagnosis of hysteria has existed for at least four-thousand years, with roots in the ancient Greek word hysterikos, referring to diseases of the womb. In the sixteenth-century medical discourses, female hysteria was caused by excess pollution of the womb, with fluids that were labelled ‘female sperm' as the probable cause. In the work of Shakespeare, there is a reference to hysterica passio, a term used by King Lear to self-diagnose his affliction. Shakespeare shows how a disease associated with women, and the ‘wandering womb' phenomenon could have been spoken of in an associative way. At this time, there is a transformation of the nature of hysteria from a neurological consequence of the sick womb, to sexual deviance. Portrayals of the male deviant would evolve by the Victorian era, concurrent with the diagnosis of ‘spermatorrhea'. There are very direct correspondences between the hysteria of spermatorrhea and the notion in Western medicine of the direct links between female hysteria and too much or not enough sexual energy release. Hysteria in both sexes was famously diagnosed and catalogued by Jean-Martin Charcot at the end of the nineteenth century. By the twentieth century, hysteria was also depicted as a disorder of gender as well as sexuality. i 2014 S. Karger AG, Basel
Eosinophilic Granulomatosis with Polyangiitis and Diffuse Gastrointestinal Involvement
Authors: Franco Diana L. , Ruff Kevin , Mertz Lester , Lam-Himlin Dora M. , Heigh Russell
Published: October 2014

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome, is a rare systemic small- and medium-sized-vessel vasculitis, characterized by the presence of severe asthma as well as blood and tissue eosinophilia. Gastrointestinal (GI) symptoms, like diarrhea and abdominal pain, are common; however, there are few reports of histologic evidence of GI involvement. We report the case of a patient on treatment for EGPA who presented with recurrent small bowel obstruction and choledocholithiasis. Biopsies of the esophagus, small bowel and common bile duct showed diffuse eosinophilia, with clear EGPA in the GI tract. Improved awareness of GI EGPA may allow for timely management of this disorder.
Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis
Authors: Subramanian Manikandan , Thorp Edward , Tabas Ira
Published: October 2014

Rationale:

Granulocyte macrophage colony-stimulating factor (GM-CSF, Csf2) is a growth factor for myeloid-lineage cells that has been implicated in the pathogenesis of atherosclerosis and other chronic inflammatory diseases. However, the role of GM-CSF in advanced atherosclerotic plaque progression, the process that gives rise to clinically dangerous plaques, is unknown.

Objective:

To understand the role of GM-CSF in advanced atherosclerotic plaque progression.

Methods and Results:

Ldlr
−/−
mice and
Csf2
−/−
Ldlr
−/−
mice were fed a Western-type diet for 12 weeks, and then parameters of advanced plaque progression in the aortic root were quantified. Lesions from the GM-CSF–deficient mice showed a substantial decrease in 2 key hallmarks of advanced atherosclerosis, lesional macrophage apoptosis and plaque necrosis, which indicates that GM-CSF promotes plaque progression. Based on a combination of in vitro and in vivo studies, we show that the mechanism involves GM-CSF–mediated production of interleukin-23, which increases apoptosis susceptibility in macrophages by promoting proteasomal degradation of the cell survival protein Bcl-2 (B-cell lymphoma 2) and by increasing oxidative stress.

Conclusions:

In low-density lipoprotein–driven atherosclerosis in mice, GM-CSF promotes advanced plaque progression by increasing macrophage apoptosis susceptibility. This action of GM-CSF is mediated by its interleukin-23–inducing activity rather than its role as a growth factor.
MicroRNA Expression in Circulating Microvesicles Predicts Cardiovascular Events in Patients With Coronary Artery Disease
Authors: Jansen Felix , Yang Xiaoyan , Proebsting Sebastian , Hoelscher Marion , Przybilla David , Baumann Katharina , Schmitz Theresa , Dolf Andreas , Endl Elmar , Franklin Bernardo S. , Sinning Jan‐Malte , Vasa‐Nicotera Mariuca , Nickenig Georg , Werner Nikos
Published: October 2014

Background

Circulating micro
RNA
s (mi
RNA
s) are differentially regulated and selectively packaged in microvesicles (MVs). We evaluated whether circulating vascular and endothelial mi
RNA
s in patients with stable coronary artery disease have prognostic value for the occurrence of cardiovascular (
CV
) events.

Methods and Results

Ten mi
RNA
s involved in the regulation of vascular performance—miR‐126, miR‐222, miR‐let7d, miR‐21, miR‐20a, miR‐27a, miR‐92a, miR‐17, miR‐130, and miR‐199a—were quantified in plasma and circulating
MV
s by reverse transcription polymerase chain reaction in 181 patients with stable coronary artery disease. The median duration of follow‐up for major adverse
CV
event–free survival was 6.1 years (range: 6.0–6.4 years). Events occurred in 55 patients (31.3%). There was no significant association between
CV
events and plasma level of the selected mi
RNA
s. In contrast, increased expression of miR‐126 and miR‐199a in circulating
MV
s was significantly associated with a lower major adverse
CV
event rate. In univariate analysis, above‐median levels of miR‐126 in circulating
MV
s were predictors of major adverse
CV
event–free survival (hazard ratio: 0.485 [95%
CIAUTHOR
: Is 95%
CI
correct?: 0.278 to 0.846];
P
=0.007) and percutaneous coronary interventions (hazard ratio: 0.458 [95%
CI
: 0.222 to 0.945];
P
=0.03). Likewise, an increased level of miR‐199a in circulating
MV
s was associated with a reduced risk of major adverse
CV
events (hazard ratio: 0.518 [95%
CI
: 0.299 to 0.898];
P
=0.01) and revascularization (hazard ratio: 0.439 [95%
CI
: 0.232 to 0.832];
P
=0.01) in univariate analysis. mi
RNA
expression analysis in plasma compartments revealed that miR‐126 and miR‐199a are present mainly in circulating
MV
s.
MV
‐sorting experiments showed that endothelial cells and platelets were found to be the major cell sources of
MV
s containing miR‐126 and miR‐199a, respectively.

Conclusion

MV
s containing miR‐126 and miR‐199a but not freely circulating mi
RNA
expression predict the occurrence of
CV
events in patients with stable coronary artery disease.
Comparative Analysis of Legal Guarantees of Educational Rights of National Minorities and Migrants in Europe
Authors: Ulasiuk Iryna
Published: October 2014

A difference between a framework protecting national minorities established by the Versailles treaties and a framework protecting minorities originating from migration was blurred in the Universal Declaration of Human Rights, which adopted an all-inclusive approach to human rights. The present article is an attempt to research (a) what exactly the differences between the instruments protecting national minorities and the instruments protecting migrants are in one specific area, education, and (b) to what extent the general inclusiveness of human rights instruments has influenced or should influence the specific instruments pertaining to the protection of educational rights of migrants and national minorities.
Protecting Children’s Rights in Asian Tourism
Authors: Johnson Afrooz Kaviani
Published: October 2014

International attention was first drawn to horrifying accounts of children being sexually exploited by foreign tourists in South East Asia in the early 1990s. This article reviews progress over the last two decades to combat this crime. With tourism reaching record levels and the relative vulnerability of children in South East Asia, I contend it is an opportune time to re-examine the response. Moving forwards, prevention initiatives must better address underlying vulnerabilities and acknowledge the indivisibility and interrelationship of children’s rights granted under international human rights law. This means broadening the response to address other disturbing violations of children’s rights in the tourism context, such as child labour and ‘orphanage tourism’. Those with the potential positively to influence the tourism environment must also be engaged in ‘child safe tourism’ as part of the wider commitment to responsible tourism and the protection of human rights.
Assessing Compliance with the crc
Authors: Heymann Jody , McNeill Kristen , Raub Amy
Published: October 2014

Currently, the report-based monitoring system of the crc provides a wealth of qualitative information about country performance, but not in a form that is frequently updated, easily analysable and comparable across countries and over time. To date, a broad range of quantitatively comparable indicators of laws and policies relevant to the crc have not been widely available. Through the world Policy Analysis Center, we have collected and analysed primary legislative texts, international reports and other sources to create such indicators for all States Parties. In this article, we draw on this new data set to propose a complementary approach to monitoring progress on crc obligations using quantitatively analysable indicators of law and policy, and operationalise a sample set of indicators to demonstrate the feasibility and utility of this approach in assessing country action on children’s rights and compliance with the crc.
Pseudoceros astrorum, a new species of Polycladida (Cotylea, Pseudocerotidae) from Northeastern Brazil
Authors: BULNES VERONICA N. , TORRES YAN
Published: November 2014

Pseudoceros astrorum n. sp. is characterized by a smooth dorsal surface with a brown ground colour, and with net-like pattern of small black granules, white spots of different sizes uniformly distributed, a thin black sub-marginal band, and a white marginal rim. The pseudotentacles are dark brown with white tips and the anterior margin and cerebral region is devoid of pigmentation. The male system is characterised by conspicuous spermiducal bulbs, a conical curved penis stylet, and the sucker lies more or less posterior. With this contribution, the number of known species from Brazil is now 72, and has created new interest in the lesser-known polyclad fauna from the northeast coast of Brazil.
Impact of Identification Method on the Inferred Characteristics and Variability of Australian East Coast Lows
Authors: Pepler Acacia S. , Di Luca Alejandro , Ji Fei , Alexander Lisa V. , Evans Jason P. , Sherwood Steven C.
Published: October 2014

The Australian east coast low (ECL) is both a major cause of damaging severe weather and an important contributor to rainfall and dam inflow along the east coast, and is of interest to a wide range of groups including catchment managers and emergency services. For this reason, several studies in recent years have developed and interrogated databases of east coast lows using a variety of automated cyclone detection methods and identification criteria. This paper retunes each method so that all yield a similar event frequency within the ECL region, to enable a detailed intercomparison of the similarities, differences, and relative advantages of each method. All methods are shown to have substantial skill at identifying ECL events leading to major impacts or explosive development, but the choice of method significantly affects both the seasonal and interannual variation of detected ECL numbers. This must be taken into consideration in studies on trends or variability in ECLs, with a subcategorization of ECL events by synoptic situation of key importance.