bluuebunny/crossref_metadata_2025_split huggingface dataset:
F4F
Authors: Sridharan Manu , Artzi Shay , Pistoia Marco , Guarnieri Salvatore , Tripp Omer , Berg Ryan 
Published: December 2011

This paper presents F4F (Framework For Frameworks), a system for effective taint analysis of framework-based web applications. Most modern web applications utilize one or more web frameworks, which provide useful abstractions for common functionality. Due to extensive use of reflective language constructs in framework implementations, existing static taint analyses are often ineffective when applied to framework-based applications. While previous work has included ad hoc support for certain framework constructs, adding support for a large number of frameworks in this manner does not scale from an engineering standpoint.
F4F employs an initial analysis pass in which both application code and configuration files are processed to generate a specification of framework-related behaviors. A taint analysis engine can leverage these specifications to perform a much deeper, more precise analysis of framework-based applications. Our specification language has only a small number of simple but powerful constructs, easing analysis engine integration. With this architecture, new frameworks can be handled with no changes to the core analysis engine, yielding significant engineering benefits.
We implemented specification generators for several web frameworks and added F4F support to a state-of-the-art taint-analysis engine. In an experimental evaluation, the taint analysis enhanced with F4F discovered 525 new issues across nine benchmarks, a harmonic mean of 2.10X more issues per benchmark. Furthermore, manual inspection of a subset of the new issues showed that many were exploitable or reflected bad security practice.
On the theory and potential of LRU-MRU collaborative cache management
Authors: Gu Xiaoming , Ding Chen 
Published: December 2011

The goal of cache management is to maximize data reuse. Collaborative caching provides an interface for software to communicate access information to hardware. In theory, it can obtain optimal cache performance.
In this paper, we study a collaborative caching system that allows a program to choose different caching methods for its data. As an interface, it may be used in arbitrary ways, sometimes optimal but probably suboptimal most times and even counter productive. We develop a theoretical foundation for collaborative caches to show the inclusion principle and the existence of a distance metric we call LRU-MRU stack distance. The new stack distance is important for program analysis and transformation to target a hierarchical collaborative cache system rather than a single cache configuration. We use 10 benchmark programs to show that optimal caching may reduce the average miss ratio by 24%, and a simple feedback-driven compilation technique can utilize collaborative cache to realize 50% of the optimal improvement.
Compartmental memory management in a modern web browser
Authors: Wagner Gregor , Gal Andreas , Wimmer Christian , Eich Brendan , Franz Michael 
Published: December 2011

Since their inception, the usage pattern of web browsers has changed substantially. Rather than sequentially navigating static web sites, modern web browsers often manage a large number of simultaneous tabs displaying dynamic web content, each of which might be running a substantial amount of client-side JavaScript code. This environment introduced a new degree of parallelism that was not fully embraced by the underlying JavaScript virtual machine architecture. We propose a novel abstraction for multiple disjoint JavaScript heaps, which we call compartments. We use the notion of document origin to cluster objects into separate compartments.
Objects within a compartment can reference each other directly. Objects across compartments can only reference each other through wrappers. Our approach reduces garbage collection pause times by permitting collection of sub-heaps (compartments), and we can use cross-compartment wrappers to enforce cross origin object access policy.
Methylated RASSF1a Is the First Specific DNA Marker for Minimal Residual Disease Testing in Neuroblastoma
Authors: Stutterheim Janine , Ichou Fatima Ait , den Ouden Emmy , Versteeg Rogier , Caron Huib N. , Tytgat Godelieve A.M. , van der Schoot C. Ellen 
Published: December 2011

Abstract
Purpose: PCR-based detection of minimal residual disease (MRD) in neuroblastoma (NB) is presently based on NB-specific transcripts. However, the expression of these targets varies between patients and upon treatment, and only PHOX2B is truly specific. RASSF1a is methylated (RASSF1aM) in NB, and we investigated whether it can serve as a specific and stable DNA MRD marker.
Patients and Methods: The RASSF1aM-specific quantitative real-time PCR was tested on control bone marrow (BM; n = 50), on 71 NB tumors, and on 159 clinical BM samples at diagnosis and at follow-up of 77 patients. Results were compared with a panel of RNA markers and correlated with prognosis.
Results: RASSF1aM was present in all stage 4 and 4s tumors (n = 50) and in 86% stages 1 to 3 tumors (n = 21). The level of methylation in stage 4 NB was correlated with overall survival (P = 0.02). RASSF1aM–PCR was highly specific (only 1 amplification in 50 control samples tested in triplicate) and had a similar sensitivity as the RNA-based PCRs, as shown on clinical samples. Moreover, RASSF1aM enabled accurate quantification without need for the original tumor.
Conclusions: RASSF1aM is a novel, highly specific DNA marker for MRD detection in NB, equal to PHOX2B in specificity and sensitivity, and better suitable for MRD quantification. We propose to include RASSF1aM in further prospective MRD studies in NB alongside RNA MRD markers. In addition, this assay might also be applicable for detection of circulating tumor cells in patients with other cancers withRASSF1aM such as breast or lung cancer. Clin Cancer Res; 18(3); 808–14. ©2011 AACR.
A Genome-Wide Association Study of Overall Survival in Pancreatic Cancer Patients Treated with Gemcitabine in CALGB 80303
Authors: Innocenti Federico , Owzar Kouros , Cox Nancy L. , Evans Patrick , Kubo Michiaki , Zembutsu Hitoshi , Jiang Chen , Hollis Donna , Mushiroda Taisei , Li Liang , Friedman Paula , Wang Liewei , Glubb Dylan , Hurwitz Herbert , Giacomini Kathleen M. , McLeod Howard L. , Goldberg Richard M. , Schilsky Richard L. , Kindler Hedy L. , Nakamura Yusuke , Ratain Mark J. 
Published: December 2011

Abstract
Background and Aims: Cancer and Leukemia Group B 80303 was a randomized, phase III study in patients with advanced pancreatic cancer treated with gemcitabine plus either bevacizumab or placebo. We prospectively collected germline DNA and conducted a genome-wide association study (GWAS) using overall survival (OS) as the endpoint.
Experimental Design: DNA from 351 patients was genotyped for more than 550,000 single-nucleotide polymorphisms (SNP). Associations between OS and SNPs were investigated using the log-linear 2-way multiplicative Cox proportional hazards model. The subset of 294 genetically European patients was used for the primary analysis.
Results: A nonsynonymous SNP in interleukin (IL)17F (rs763780, H161R) and an intronic SNP in strong linkage disequilibrium (rs7771466) were associated with OS using genome-wide criteria (P ≤ 10−7). Median OS was significantly shorter (P = 2.61 × 10−8) for the rs763780 heterozygotes [3.1 months; 95% confidence interval (CI), 2.3–4.3] than for the patients without this variant (6.8 months; 95% CI, 5.8–7.3). After adjustment by stratification factors, the P value for the association was 9.51 × 10−7.
Conclusions: The variant 161R form of IL-17F is a natural antagonist of the antiangiogenic effects of wild-type 161H IL-17F, and angiogenesis may play an important role in the metastatic spread of pancreatic cancer. In this preliminary study, we hypothesize that the angiogenetic potential of pancreatic cancers in patients with variant IL-17F is higher than that of tumors in patients with wild-type IL-17F, conferring worse prognosis. This exploratory GWAS may provide the foundation for testing the biology and clinical effects of novel genes and their heritable variants through mechanistic and confirmatory studies in pancreatic cancer. Clin Cancer Res; 18(2); 577–84. ©2011 AACR.
Migraine Mutations Increase Stroke Vulnerability by Facilitating Ischemic Depolarizations
Authors: Eikermann-Haerter Katharina , Hyun Lee Jeong , Yuzawa Izumi , Liu Christina H. , Zhou Zhipeng , Kyoung Shin Hwa , Zheng Yi , Qin Tao , Kurth Tobias , Waeber Christian , Ferrari Michel D. , van den Maagdenberg Arn M.J.M. , Moskowitz Michael A. , Ayata Cenk 
Published: December 2011

Background—
Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms.

Methods and Results—

Here, we show that FHM type 1 (FHM1) mutations in Ca
V
2.1 voltage-gated Ca
2+
channels render the brain more vulnerable to ischemic stroke. Compared with wild-type mice, 2 FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist.

Conclusions—
We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk.
Extramedullary Hematopoiesis Generates Ly-6C
high
Monocytes That Infiltrate Atherosclerotic Lesions
Authors: Robbins Clinton S. , Chudnovskiy Aleksey , Rauch Philipp J. , Figueiredo Jose-Luiz , Iwamoto Yoshiko , Gorbatov Rostic , Etzrodt Martin , Weber Georg F. , Ueno Takuya , van Rooijen Nico , Mulligan-Kehoe Mary Jo , Libby Peter , Nahrendorf Matthias , Pittet Mikael J. , Weissleder Ralph , Swirski Filip K. 
Published: December 2011

Background—

Atherosclerotic lesions are believed to grow via the recruitment of bone marrow–derived monocytes. Among the known murine monocyte subsets, Ly-6C
high
monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here, we hypothesized that the bone marrow outsources the production of Ly-6C
high
monocytes during atherosclerosis.

Methods and Results—

Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells progressively relocate from the bone marrow to the splenic red pulp, where they encounter granulocyte macrophage colony-stimulating factor and interleukin-3, clonally expand, and differentiate to Ly-6C
high
monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. On lesional infiltration, Ly-6C
high
monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells.

Conclusions—
Our findings indicate that extramedullary sites supplement the hematopoietic function of the bone marrow by producing circulating inflammatory cells that infiltrate atherosclerotic lesions.
Leadership Development for Women in New Zealand Universities
Authors: Harris Candice A. , Leberman Sarah I. 
Published: December 2011

The Problem. Women continue to be underrepresented in senior academic and general staff positions in universities internationally, and New Zealand universities are no different. In addition, there is limited empirical research on leadership development programs for women. The Solution. This article adds to knowledge in the area by describing and discussing the outcomes of the national New Zealand Women in Leadership (NZWIL) program, which is now in its 5th year of operation. A longitudinal case study approach has been adopted including surveys, phone interviews, and an independent evaluation. The findings suggest that the program has been successful on both an individual and organizational level. Individually, participants have increased their self-confidence and networking skills, enabling them, for example, to apply for promotion and gain it. The Stakeholders. Postsecondary leaders, human resource development (HRD), and leadership development professionals can learn from the findings of this program and adapt them to their context.
The Cranston Library, Reigate: The First Three Hundred Years
Authors: Thomas Andrea , Ely Hilary 
Published: December 2011

The Cranston Library, Reigate, is a remarkable example of an early eighteenth-century parish library, which retains almost all of its original collection in its original location. It was founded by Revd Andrew Cranston in 1701 and was established as a charitable trust in 1708. It was the only library specifically exempted from the provisions of the 1708/09 Parochial Libraries Act. From the start it operated as a public lending library and, until the establishment of the Surrey County Library Service in the 1920s, it provided intellectual stimulus for all the people of Reigate, not just the clergy. The collection is not entirely theological, but contains some 2350 volumes on a wide range of subjects. The Library's records of donors, borrowers, and trustees, and the books themselves, provide a fascinating insight into the intellectual climate of the period. In the twenty-first century we endeavour to maintain the Library in good condition as a jewel of the local heritage, and as an academic resource for scholars. All our trustees and helpers are volunteers and we have no financial endowment behind us. We are therefore reliant on the generosity of our supporters and the good offices of the Reigate Decorative and Fine Arts Society and the Cowlishaw conservation workshop to achieve our aims. The opportunities and pitfalls of the digital age present the current trustees with many new challenges as we try to balance the demands of access with security, and preservation with utilization. We take inspiration from our founder and seek to ensure that the Library should flourish for at least another three hundred years.
Mitochondrial dysfunction in ataxia-telangiectasia
Authors: Valentin-Vega Yasmine A. , MacLean Kirsteen H. , Tait-Mulder Jacqueline , Milasta Sandra , Steeves Meredith , Dorsey Frank C. , Cleveland John L. , Green Douglas R. , Kastan Michael B. 
Published: December 2011

AbstractAtaxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses, and its loss leads to development of T-cell malignancies. Here, we show that ATM loss also leads to intrinsic mitochondrial abnormalities in thymocytes, including elevated reactive oxygen species, increased aberrant mitochondria, high cellular respiratory capacity, and decreased mitophagy. A fraction of ATM protein is localized in mitochondria, and it is rapidly activated by mitochondrial dysfunction. Unexpectedly, allelic loss of the autophagy regulator Beclin-1 significantly delayed tumor development in ATM-null mice. This effect was not associated with rescue of DNA damage signaling but rather with a significant reversal of the mitochondrial abnormalities. These data support a model in which ATM plays direct roles in modulating mitochondrial homeostasis and suggest that mitochondrial dysfunction and associated increases in mitochondrial reactive oxygen species contribute to the cancer-prone phenotype observed in organisms lacking ATM. Thus, ataxia-telangiectasia should be considered, at least in part, as a mitochondrial disease.
Specificity and selectivity profile of EP217609: a new neutralizable dual-action anticoagulant that targets thrombin and factor Xa
Authors: Olson Steven T. , Swanson Richard , Petitou Maurice 
Published: December 2011

AbstractEP217609 is a new dual-action parenteral anticoagulant that combines an indirect factor Xa inhibitor (fondaparinux analog) and a direct thrombin inhibitor (α-NAPAP analog) in a single molecule together with a biotin tag to allow avidin neutralization. EP217609 exhibits an unprecedented pharmacologic profile in showing high bioavailability, long plasma half-life, and potent antithrombotic activity in animals without the complications of thrombin rebound. Here we report the exceptional specificity and selectivity profile of EP217609. EP217609 inhibited thrombin with rapid kinetics (kon > 107M−1s−1), a high affinity (KI = 30-40pM), and more than 1000-fold selectivity over other coagulation and fibrinolytic protease targets, comparing favorably with the best direct thrombin inhibitors known. EP217609 bound antithrombin with high affinity (KD = 30nM) and activated the serpin to rapidly (kass ∼ 106M−1s−1) and selectively (> 20-fold) inhibit factor Xa. The dual inhibitor moieties of EP217609 acted largely independently with only modest linkage effects of ligand occupancy of one inhibitor moiety on the potency of the other (∼ 5-fold). In contrast, avidin binding effectively neutralized the potency of both inhibitor moieties (20- to 100-fold). These findings demonstrate the superior anticoagulant efficacy and rapid avidin neutralizability of EP217609 compared with anticoagulants that target thrombin or factor Xa alone.
FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma
Authors: Ma Yussanne P. , van Leeuwen Flora E. , Cooke Rosie , Broeks Annegien , Enciso-Mora Victor , Olver Bianca , Lloyd Amy , Broderick Peter , Russell Nicola S. , Janus Cecile , Ashworth Alan , Houlston Richard S. , Swerdlow Anthony J. 
Published: December 2011

Abstract
Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.
Human biomonitoring on heavy metals in Ath: methodological aspects
Authors: Rebolledo Javiera , Fierens Sebastien , Versporten Ann , Brits Ethel , De Plaen Pierre , Van Nieuwenhuyse An 
Published: December 2011

Abstract
The municipality of Ath is characterised by the presence, in its center, of two non-ferrous metal industries whose emissions make local residents concerned for their health. Therefore, authorities of the Walloon Region and the municipality of Ath undertook biomonitoring to assess the impact of those industrial emissions on heavy metal body burden in humans.
This paper describes the study design and methodology used to carry out this human biomonitoring.
A random sampling was done in the general population, in two areas of Ath: an area centered around the industries and a peripheral area. The target population was children (2.5-11 years) and adults (40-60 years) without occupational exposure. The three-stage sampling procedure consisted of a mixture of both mail and telephone recruitment. Firstly, 3259 eligible people, identified from a population register, were mailed an introductory letter. In a second stage, eligible individuals were contacted by phone to propose them to participate in the study. They were randomly contacted until the required sample size was obtained. In the third stage, a second mail was sent to those who agreed to participate with a questionnaire to be filled out. Finally, biological samples (blood and urine) from 278 persons were collected. The final participation rate of this study was 24%.
This sampling procedure, especially designed for the purpose of this biomonitoring study in Ath, allowed us to recruit a sample representative of the population of children and adults of Ath, reaching the expected sample size in a short period of time.
How can the results of a qualitative process evaluation be applied in management, improvement and modification of a preventive community trial? The IHHP Study
Authors: Sarrafzadegan Nizal , Rabiei Katayoun , Alavi Mousa , Abedi Heidarali , Zarfeshani Sonia 
Published: December 2011

Abstract

Background
This study reports the results of the qualitative process evaluation (PE) of the Isfahan Healthy Heart Program (IHHP), an integrated community-based trial for prevention and control of non-communicable diseases in Iran.

Methods
The study explored the overall quality of program implementation. The participants, including designers of IHHP, stakeholders and community members (n = 60) were purposefully recruited from the intervention areas. Data collected from semi-structured interviews and field notes were analyzed using a modified thematic analysis.

Results
Four main themes were identified. Our findings highlighted the key role of the resources as both facilitating and hindering factors. IHHP directors faced incompatibilities arising from negative perceptions/attitudes which resulted in decreased adherence to the program. Hence various strategies were used to motivate, strengthen and organize the human workforce implementing the program.

Conclusion
Recommendations arising from evaluation of the program were used in subsequent stages of implementation. Qualitative research is an important component of community trials which can improve their implementation.
TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling
Authors: Brase Jan C , Johannes Marc , Mannsperger Heiko , Fälth Maria , Metzger Jennifer , Kacprzyk Lukasz A , Andrasiuk Tatjana , Gade Stephan , Meister Michael , Sirma Hüseyin , Sauter Guido , Simon Ronald , Schlomm Thorsten , Beißbarth Tim , Korf Ulrike , Kuner Ruprecht , Sültmann Holger 
Published: December 2011

Abstract

Background

TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.

Methods
We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays.

Results
Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors.

Conclusions
The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy.