bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are transit users loyal? Revelations from a hazard model based on smart card data
Authors: Trépanier Martin , Habib Khandker M.N. , Morency Catherine 
Published: June 2012

Smart card fare collection systems for public transit produce a huge quantity of data on a daily basis. The ability to follow the use of a single card throughout the months gives the opportunity of measuring the loyalty of the individual to the service. Then, operators can have quantitative knowledge of the loyalty in their network. However, it is also important to know what are the factors that influence the survival of the users. This paper presents the application of a discrete time hazard model to 5 years of data of a medium-size transit authority in Canada. The concept of the hazard model relates to the fact that the probability to continue the use of a smart card by user i, at time t, is conditional to the probability of not cancelling the card before the time period. Hence, its use is appropriate in this case. Results for the regular adult fare show that loyalty is positively influenced by residential density and by the transit share in the area. A younger population will also be retained longer in the system. However, a high unemployment rate has a negative impact on survival. A high share of transit and walk trips is also affecting the loyalty, suggesting that the retention is reduced when there are more mode choices available to the commuter.
Analyzing volatile organic siloxanes in landfill biogas
Authors: Clark Chris , Zytner Richard G. , McBean Edward 
Published: June 2012

Many municipalities are turning to landfill biogas to generate electricity. A major challenge is the presence of volatile cyclic organic siloxanes in the biogas stream, which upon combustion form silica deposits, decreasing the lifetime and warranty of reciprocating engines and turbines. With literature reporting that the analysis of biogas for siloxanes is complex, an investigation was completed to identify best practices for measuring siloxane concentrations in the biogas. The result is an easy-to-use collection and analytical technique that used commercially available XAD-2 resin ORBO® tubes to capture siloxanes through sorption. Following desorption, analysis was done on a gas chromatograph equipped with a flame ionization detector. Using the developed technique at the Region of Waterloo landfill, the sampled biogas showed the presence of D4-siloxane at an average concentration of 37.6 ± 1.7 mg/m3, while the D5-siloxane concentration was 21.9 ± 1.2 mg/m3. These measured concentrations were higher than those reported by an accredited lab. Investigation suggests that the use of Tedlar® bags by the outside lab to collect the biogas sample affected the reliability and variability of the latter approach.
CpG oligodeoxynucleotides discriminately enhance binding capacity of human naïve B cells to Hepatitis B virus epitopes
Authors: Bai Jian-ying , Yang Yong-tao , Zhu Rong , Wang Yi-qin , Tian Yin , Li Xiao-huan , Wang Rong-quan 
Published: June 2012

CpG oligodeoxynucleotides (CpG ODN) have the potential to enhance the antigen-presenting cells function of human naïve B cells. In this study, we aim to define the effect of CpG ODNs on the binding capacity of human naïve B cells for different Hepatitis B virus (HBV) epitopes. Three HLA-A2 restricted epitopes were selected to incubate with CpG ODN-primed human naïve B cells. Binding capacity for each epitope and expression of CD80, CD86, class I major histocompatibility complex (MHC), and class II MHC of naïve B cells was tested, respectively, by flow cytometry. CpG ODNs, especially ODN 2216, enhanced the binding capacity of human naïve B cells for HBV epitopes (p < 0.01), and induced markedly higher expression of CD80, CD86, class I MHC, and class II MHC. The binding capacity of CpG-treated naive B cells for each epitope was significantly different. In all the 3 subjects, CpG ODN 2216-primed naïve B cells showed the highest binding ability for Env172–180 compared with the other epitopes with a high expression of co-stimulatory and MHC molecules. CpG ODN showed the potential to selectively enhance the binding capacity of human naïve B cells for HBV epitopes. These results suggest new strategies for development of vaccine design.
Metabolic profiling of Staphylococcus aureus cultivated under aerobic and anaerobic conditions with 1H NMR-based nontargeted analysis
Authors: Sun Ji-Lu , Zhang Shao-Kang , Chen Jing-Yu , Han Bei-Zhong 
Published: June 2012

Staphylococcus aureus is a major pathogen in the medical area and food-producing sector. Detailed analyses of its basic cell physiology will help comprehensively understand this pathogen, which will be useful for developing novel diagnostic and treatment tools. Oxygen is one of the most crucial growth-limiting factors for S. aureus. In this study, to characterize and distinguish metabolic profiles of S. aureus cultivated under aerobic and anaerobic conditions, nontargeted analyses of both types of cultures were carried out using 1H nuclear magnetic resonance spectroscopy. Fifty compounds were identified by Chenomx software. Characteristics of metabolic profiles were achieved by using principal components analysis. During aerobic growth, S. aureus mainly consumed glucose, alanine, arginine, glycine, isoleucine, leucine, phenylalanine, and acetate. Meanwhile, it accumulated 17 metabolites, mainly 2-oxoglutarate, isobutyrate, isovalerate, succinate, and ethanol. Under anaerobic condition, S. aureus mainly consumed glucose, arginine, and threonine. Meanwhile, it accumulated 13 metabolites, mainly ethanol, lactate, and ornithine. The representative metabolites that could most significantly differentiate metabolic profiles of S. aureus were isobutyrate, isovalerate, and succinate in aerobic cultivation; and lactate, ethanol, and ornithine in anaerobic cultivation. Among these metabolites, isobutyrate and ornithine were present only in aerobic and anaerobic culture, respectively.
Taxonomic and symbiotic diversity of bacteria isolated from nodules ofAcacia tortilissubsp.raddianain arid soils of Tunisia
Authors: Fterich A. , Mahdhi M. , Lafuente A. , Pajuelo E. , Caviedes M.A. , Rodriguez-Llorente I.D , Mars M. 
Published: June 2012

A collection of rhizobia isolated from Acacia tortilis subsp. raddiana nodules from various arid soils in Tunisia was analyzed for their diversity at both taxonomic and symbiotic levels. The isolates were found to be phenotypically diverse. The majority of the isolates tolerated 3% NaCl and grew at 40 °C. Genetic characterization emphasized that most of the strains (42/50) belong to the genus Ensifer , particularly the species Ensifer meliloti , Ensifer garamanticus , and Ensifer numidicus . Symbiotic properties of isolates showed diversity in their capacity to nodulate their host plant and to fix atmospheric nitrogen. The most effective isolates were closely related to E. garamanticus. Nodulation tests showed that 3 strains belonging to Mesorhizobium genus failed to renodulate their host plant, which is surprising for symbiotic rhizobia. Furthermore, our results support the presence of non-nodulating endophytic bacteria belonging to the Acinetobacter genus in legume nodules.
Protective efficacy of aMycoplasma pneumoniaeP1C DNA vaccine fused with the B subunit ofEscherichia coliheat-labile enterotoxin
Authors: Zhu Cuiming , Wang Shiping , Hu Shihai , Yu Minjun , Zeng Yanhua , You Xiaoxing , Xiao Jinhong , Wu Yimou 
Published: June 2012

In the present study, we investigated the immunomodulatory responses of a DNA vaccine constructed by fusing Mycoplasma pneumoniae P1 protein carboxy terminal region (P1C) with the Escherichia coli heat-labile toxin B subunit (LTB). BALB/c mice were immunized by intranasal inoculation with control DNAs, the P1C DNA vaccine or the LTB–P1C fusion DNA vaccine. Levels of the anti-M. pneumoniae antibodies and levels of interferon-γ and IL-4 in mice were increased significantly upon inoculation of the LTB–P1C fusion DNA vaccine when compared with the inoculation with P1C DNA vaccine. The LTB–P1C fusion DNA vaccine efficiently enhanced the M. pneumoniae-specific IgA and IgG levels. The IgG2a/IgG1 ratio was significantly higher in bronchoalveolar lavages fluid and sera from mice fusion with LTB and P1C than mice receiving P1C alone. When the mice were challenged intranasally with 107CFU M. pneumoniae strain (M129), the LTB–P1C fusion DNA vaccine conferred significantly better protection than P1C DNA vaccine (P < 0.05), as suggested by the results, such as less inflammation, lower histopathological score values, lower detectable number of M. pneumoniae strain, and lower mortality of challenging from 5 × 108CFU M. pneumoniae. These results indicated that the LTB–P1C fusion DNA vaccine efficiently improved protective efficacy against M. pneumoniae infection and effectively attenuated development of M. pneumoniae in mice.
Integrating trust management and access control in data-intensive Web applications
Authors: Vimercati Sabrina De Capitani Di , Foresti Sara , Jajodia Sushil , Paraboschi Stefano , Psaila Giuseppe , Samarati Pierangela 
Published: June 2012

The widespread diffusion of Web-based services provided by public and private organizations emphasizes the need for a flexible solution for protecting the information accessible through Web applications. A promising approach is represented by credential-based access control and trust management. However, although much research has been done and several proposals exist, a clear obstacle to the realization of their benefits in data-intensive Web applications is represented by the lack of adequate support in the DBMSs. As a matter of fact, DBMSs are often responsible for the management of most of the information that is accessed using a Web browser or a Web service invocation.
In this article, we aim at eliminating this gap, and present an approach integrating trust management with the access control of the DBMS. We propose a trust model with a SQL syntax and illustrate an algorithm for the efficient verification of a delegation path for certificates. Our solution nicely complements current trust management proposals allowing the efficient realization of the services of an advanced trust management model within current relational DBMSs. An important benefit of our approach lies in its potential for a robust end-to-end design of security for personal data in Web scenario, where vulnerabilities of Web applications cannot be used to violate the protection of the data residing on the database server. We also illustrate the implementation of our approach within an open-source DBMS discussing design choices and performance impact.
Axiom based architecture
Authors: Mueller Conrad 
Published: June 2012

The paper proposes an axiom based architecture as an alternative to the von Neumann model. The model has many desirable properties: fine-grained parallelism, simple semantics, better security and easy of programming. The empirical research gives some indication of its performance potential.
A description is given as to how algebraic arithmetic expressions of relations can be broken up into primitive expressions consisting of a single operation. These primitive relations are shown to be sufficient to describe a Turing machine. Eight inference rules are given that define how the primitive relations can be evaluated. An outline is given of an architecture based on these inference rules. Finally a brief description is given of an experimental emulation and empirical evaluation of the architecture.
Instead of manipulating data or values by applying instructions or functions, computation is applying existing elements to relations to create new elements. The element's identifier determines which relations the element applies to. The relation determines the identifier of the new element and the operation that needs to be applied to create the value of the new element.
The conceptually indices are different in this model. Instead of seeing an index as an offset into an array, an index is seen as part of the element identifier. This enables infinitely many relations to be defined between unique sets using universal quantifiers. Thus every element, or value, computed has a unique description.
Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids
Authors: Jiang Weiqin , Zhu Zongjian , McGinley John N. , El Bayoumy Karam , Manni Andrea , Thompson Henry J. 
Published: June 2012

Abstract
An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to inhibit the development of mammary cancer in animal models. However, the molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown. Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty acids on cell signaling in a rat model of chemically induced mammary carcinoma. Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6 treatment group compared with the low n-3:n-6 treatment group. These changes were associated with decreased cyclin-D1 and phospho-retinoblastoma protein expression and increased levels of cyclin-dependent kinase inhibitors, CIP1 (p21) and KIP1 (p27). In addition, the apoptotic index was increased in carcinomas from the high n-3:n-6 group and was associated with elevated apoptotic protease-activating factor 1 and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein expression were consistent with reduced inflammation and suppressed mTOR activity, and the molecular signature associated with high n-3:n-6 treatment revealed changes in PPARγ activation and suppression of lipid synthesis. Together, our findings indicate that the molecular effects of high dietary n-3 to n-6 ratios are heterogeneous in nature but point to consistent changes in lipid metabolism pathways, which may serve as potential therapeutic targets for cancer prevention and control. This study identifies the pathways modulated by dietary fatty acid ratios in a rat model of breast cancer, with implications for cancer prevention. Cancer Res; 72(15); 3795–806. ©2012 AACR.
Complete Longitudinal Analyses of the Randomized, Placebo-Controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor following Imatinib Failure
Authors: Demetri George D. , Garrett Christopher R. , Schöffski Patrick , Shah Manisha H. , Verweij Jaap , Leyvraz Serge , Hurwitz Herbert I. , Pousa Antonio Lopez , Le Cesne Axel , Goldstein David , Paz-Ares Luis , Blay Jean-Yves , McArthur Grant A. , Xu Qiang (Casey) , Huang Xin , Harmon Charles S. , Tassell Vanessa , Cohen Darrel P. , Casali Paolo G. 
Published: June 2012

Abstract
Purpose: To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes.
Experimental Design: Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore cross-over impact. Circulating levels of angiogenesis biomarkers were analyzed.
Results: In total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103 of whom crossed over to open-label sunitinib. Conventional statistical analysis showed that OS converged in the sunitinib and placebo arms (median 72.7 vs. 64.9 weeks; HR, 0.876; P = 0.306) as expected, given the cross-over design. RPSFT analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262–1.134; P = 0.306). No new safety concerns emerged with extended sunitinib treatment. No consistent associations were found between the pharmacodynamics of angiogenesis-related plasma proteins during sunitinib treatment and clinical outcome.
Conclusions: The cross-over design provided evidence of sunitinib clinical benefit based on prolonged time to tumor progression during the double-blind phase of this trial. As expected, following cross-over, there was no statistical difference in OS. RPSFT analysis modeled the absence of cross-over, estimating a substantial sunitinib OS benefit relative to placebo. Long-term sunitinib treatment was tolerated without new adverse events. Clin Cancer Res; 18(11); 3170–9. ©2012 AACR.
The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells
Authors: Landau Heather J. , McNeely Samuel C. , Nair Jayasree S. , Comenzo Raymond L. , Asai Takashi , Friedman Hillel , Jhanwar Suresh C. , Nimer Stephen D. , Schwartz Gary K. 
Published: June 2012

Abstract
DNA cross-linking agents are frequently used in the treatment of multiple myeloma–generating lesions, which activate checkpoint kinase 1 (Chk1), a critical transducer of the DNA damage response. Chk1 activation promotes cell survival by regulating cell-cycle arrest and DNA repair following genotoxic stress. The ability of AZD7762, an ATP-competitive Chk1/2 inhibitor to increase the efficacy of the DNA-damaging agents bendamustine, melphalan, and doxorubicin was examined using four human myeloma cell lines, KMS-12-BM, KMS-12-PE, RPMI-8226, and U266B1. The in vitro activity of AZD7762 as monotherapy and combined with alkylating agents and the “novel” drug bortezomib was evaluated by studying its effects on cytotoxicity, signaling, and apoptotic pathways. The Chk1/2 inhibitor AZD7762 potentiated the antiproliferative effects of bendamustine, melphalan, and doxorubicin but not bortezomib in multiple myeloma cell lines that were p53-deficient. Increased γH2AX staining in cells treated with bendamustine or melphalan plus AZD7762 indicates a greater degree of DNA damage with combined therapy. Abrogation of the G2–M checkpoint by AZD7762 resulted in mitotic catastrophe with ensuing apoptosis evidenced by PARP and caspase-3 cleavage. In summary, the cytotoxic effects of bendamustine, melphalan and doxorubicin on p53-deficient multiple myeloma cell lines were enhanced by the coadministration of AZD7762. These data provide a rationale for testing these combinations in patients with relapsed and/or refractory multiple myeloma. Mol Cancer Ther; 11(8); 1781–8. ©2012 AACR.
Characterization of the Mechanism of Action of the Pan Class I PI3K Inhibitor NVP-BKM120 across a Broad Range of Concentrations
Authors: Brachmann Saskia M. , Kleylein-Sohn Julia , Gaulis Swann , Kauffmann Audrey , Blommers Marcel J.J. , Kazic-Legueux Malika , Laborde Laurent , Hattenberger Marc , Stauffer Fabian , Vaxelaire Juliane , Romanet Vincent , Henry Chrystèle , Murakami Masato , Guthy Daniel Alexander , Sterker Dario , Bergling Sebastian , Wilson Christopher , Brümmendorf Thomas , Fritsch Christine , Garcia-Echeverria Carlos , Sellers William R. , Hofmann Francesco , Maira Sauveur-Michel 
Published: June 2012

Abstract
The pan-phosphoinositide 3-kinase (PI3K) inhibitor BKM120 was found, at high concentrations, to cause cell death in various cellular systems, irrespective of their level of PI3K addiction. Transcriptional and biochemical profiling studies were used to identify the origin of these unexpected and apparently PI3K-independent effects. At 5- to 10-fold, the concentration needed to half-maximally inhibit PI3K signaling. BKM120 treatment caused changes in expression of mitotic genes and the induction of a robust G2–M arrest. Tubulin polymerization assays and nuclear magnetic resonance-binding studies revealed that BKM120 inhibited microtubule dynamics upon direct binding to tubulin. To assess the contribution of this off-target activity vis-à-vis the antitumor activity of BKM120 in PI3K-dependent tumors, we used a mechanistic PI3K-α–dependent model. We observed that, in vivo, daily treatment of mice with doses of BKM120 up to 40 mg/kg led to tumor regressions with no increase in the mitotic index. Thus, strong antitumor activity can be achieved in PI3K-dependent models at exposures that are below those necessary to engage the off-target activity. In comparison, the clinical data indicate that it is unlikely that BKM120 will achieve exposures sufficient to significantly engage the off-target activity at tolerated doses and schedules. However, in preclinical settings, the consequences of the off-target activity start to manifest themselves at concentrations above 1 μmol/L in vitro and doses above 50 mg/kg in efficacy studies using subcutaneous tumor–bearing mice. Hence, careful concentration and dose range selection is required to ensure that any observation can be correctly attributed to BKM120 inhibition of PI3K. Mol Cancer Ther; 11(8); 1747–57. ©2012 AACR.
Protein Kinase C Inhibitor AEB071 Targets Ocular Melanoma Harboring GNAQ Mutations via Effects on the PKC/Erk1/2 and PKC/NF-κB Pathways
Authors: Wu Xinqi , Li Jingjing , Zhu Meijun , Fletcher Jonathan A. , Hodi F. Stephen 
Published: June 2012

Abstract
Somatic GNAQ mutations at codon 209 have been identified in approximately 50% of uveal melanomas and have been reported to be oncogenic through activating PLCβ/PKC/Erk1/2 pathways. We hypothesized that protein kinase C (PKC) may provide new opportunities for therapeutic targeting of uveal melanoma carrying GNAQ mutations. To test this hypothesis, uveal melanoma cells harboring wild-type or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or infected with lentivirus-expressing short hairpin RNAs (shRNA) targeting PKC isoforms. Notably, AEB071 at low micromolar concentrations significantly inhibited the growth of uveal melanoma cells harboring GNAQ mutations through induction of G1 arrest and apoptosis. However, AEB071 had little effect on uveal melanoma cells carrying wild-type GNAQ. AEB071-mediated cell inhibition in the GNAQ-mutated uveal melanoma was accompanied by inhibition of extracellular signal–regulated kinase (Erk)1/2 phosphorylation, NF-κB, decreased expression of cyclin D1, survivin, Bcl-xL, and XIAP, and increased expression of cyclin-dependent kinase inhibitor p27Kip1. AEB071 suppressed the expression of PKC α, β, δ, ϵ, and θ in GNAQ-mutated uveal melanoma cells. Our findings from shRNA-mediated knockdown studies revealed that these PKC isoforms are functionally important for uveal melanoma cells harboring GNAQ mutations. Furthermore, inhibitors of Erk1/2 and NF-κB pathways reduced viability of uveal melanoma cells. Together, our findings show that AEB071 exerts antitumor action on uveal melanoma cells carrying GNAQ mutations via targeting PKC/Erk1/2 and PKC/NF-κB pathways. Targeted PKC inhibition with drugs such as AEB071 offers novel therapeutic potential for uveal melanoma harboring GNAQ mutations. Mol Cancer Ther; 11(9); 1905–14. ©2012 AACR.