bluuebunny/crossref_metadata_2025 huggingface dataset:
Rectangular full packed format for cholesky's algorithm
Authors: Gustavson Fred G. , Waśniewski Jerzy , Dongarra Jack J. , Langou Julien
Published: May 2010

We describe a new data format for storing triangular, symmetric, and Hermitian matrices called
Rectangular Full Packed Format
(RFPF). The standard two-dimensional arrays of Fortran and C (also known as
full format
) that are used to represent triangular and symmetric matrices waste nearly half of the storage space but provide high performance via the use of Level 3 BLAS. Standard packed format arrays fully utilize storage (array space) but provide low performance as there is no Level 3 packed BLAS. We combine the good features of packed and full storage using RFPF to obtain high performance via using Level 3 BLAS as RFPF is a standard full-format representation. Also, RFPF requires exactly the same minimal storage as packed the format. Each LAPACK full and/or packed triangular, symmetric, and Hermitian routine becomes a single new RFPF routine based on eight possible data layouts of RFPF. This new RFPF routine usually consists of two calls to the corresponding LAPACK full-format routine and two calls to Level 3 BLAS routines. This means
no
new software is required. As examples, we present LAPACK routines for Cholesky factorization, Cholesky solution, and Cholesky inverse computation in RFPF to illustrate this new work and to describe its performance on several commonly used computer platforms. Performance of LAPACK full routines using RFPF versus LAPACK full routines using the standard format for both serial and SMP parallel processing is about the same while using half the storage. Performance gains are roughly one to a factor of 43 for serial and one to a factor of 97 for SMP parallel times faster using vendor LAPACK full routines with RFPF than with using vendor and/or reference packed routines.
GradientShop
Authors: Bhat Pravin , Zitnick C. Lawrence , Cohen Michael , Curless Brian
Published: May 2010

We present an optimization framework for exploring gradient-domain solutions for image and video processing. The proposed framework unifies many of the key ideas in the gradient-domain literature under a single optimization formulation. Our hope is that this generalized framework will allow the reader to quickly gain a general understanding of the field and contribute new ideas of their own.

We propose a novel metric for measuring local gradient saliency that identifies salient gradients that give rise to long, coherent edges, even when the individual gradients are faint. We present a general weighting scheme for gradient constraints that improves the visual appearance of results. We also provide a solution for applying gradient-domain filters to videos and video streams in a coherent manner.

Finally, we demonstrate the utility of our formulation in creating effective yet simple to implement solutions for various image-processing tasks. To exercise our formulation we have created a new saliency-based sharpen filter and a pseudo image-relighting application. We also revisit and improve upon previously defined filters such as nonphotorealistic rendering, image deblocking, and sparse data interpolation over images (e.g., colorization using optimization).
Modeling and rendering of impossible figures
Authors: Wu Tai-Pang , Fu Chi-Wing , Yeung Sai-Kit , Jia Jiaya , Tang Chi-Keung
Published: May 2010

This article introduces an optimization approach for modeling and rendering impossible figures. Our solution is inspired by how modeling artists construct physical 3D models to produce a valid 2D view of an impossible figure. Given a set of 3D locally possible parts of the figure, our algorithm automatically optimizes a view-dependent 3D model, subject to the necessary 3D constraints for rendering the impossible figure at the desired novel viewpoint. A linear and constrained least-squares solution to the optimization problem is derived, thereby allowing an efficient computation and rendering new views of impossible figures at interactive rates. Once the optimized model is available, a variety of compelling rendering effects can be applied to the impossible figure.
An efficient multigrid method for the simulation of high-resolution elastic solids
Authors: Zhu Yongning , Sifakis Eftychios , Teran Joseph , Brandt Achi
Published: May 2010

We present a multigrid framework for the simulation of high-resolution elastic deformable models, designed to facilitate scalability on shared memory multiprocessors. We incorporate several state-of-the-art techniques from multigrid theory, while adapting them to the specific requirements of graphics and animation applications, such as the ability to handle elaborate geometry and complex boundary conditions. Our method supports simulation of linear elasticity and corotational linear elasticity. The efficiency of our solver is practically independent of material parameters, even for near-incompressible materials. We achieve simulation rates as high as 6 frames per second for test models with 256K vertices on an 8-core SMP, and 1.6 frames per second for a 2M vertex object on a 16-core SMP.
Analysis and applications of timed service protocols
Authors: Ponge Julien , Benatallah Boualem , Casati Fabio , Toumani Farouk
Published: May 2010

Web services are increasingly gaining acceptance as a framework for facilitating application-to-application interactions within and across enterprises. It is commonly accepted that a service description should include not only the interface, but also the business protocol supported by the service. The present work focuses on the formalization of an important category of protocols that includes time-related constraints (called
timed protocols
), and the impact of time on compatibility and replaceability analysis. We formalized the following timing constraints: C-Invoke constraints define time windows within which a service operation can be invoked while M-Invoke constraints define expiration deadlines. We extended techniques for compatibility and replaceability analysis between timed protocols by using a semantic-preserving mapping between timed protocols and timed automata, leading to the identification of a novel class of timed automata, called
protocol timed automata
(PTA). PTA exhibit a particular kind of silent transition that strictly increase the expressiveness of the model, yet they are closed under complementation, making every type of compatibility or replaceability analysis decidable. Finally, we implemented our approach in the context of a larger project called ServiceMosaic, a model-driven framework for Web service life-cycle management.
A verification system for interval-based specification languages
Authors: Chen Chunqing , Dong Jin Song , Sun Jun , Martin Andrew
Published: May 2010

Interval-based specification languages have been used to formally model and rigorously reason about real-time computing systems. This usually involves logical reasoning and mathematical computation with respect to continuous or discrete time. When these systems are complex, analyzing their models by hand becomes error-prone and difficult. In this article, we develop a verification system to facilitate the formal analysis of interval-based specification languages with machine-assisted proof support. The verification system is developed using a generic theorem prover, Prototype Verification System (PVS). Our system elaborately encodes a highly expressive set-based notation, Timed Interval Calculus (TIC), and can rigorously carry out the verification of TIC models at an interval level. We validated all TIC reasoning rules and discovered subtle flaws in the original rules. We also apply TIC to model Duration Calculus (DC), which is a popular interval-based specification language, and thus expand the capacity of the verification system. We can check the correctness of DC axioms, and execute DC proofs in a manner similar to the corresponding pencil-and-paper DC arguments.
Biophysical properties of mitochondrial fusion events in pancreatic β-cells and cardiac cells unravel potential control mechanisms of its selectivity
Authors: Twig Gilad , Liu Xingguo , Liesa Marc , Wikstrom Jakob D. , Molina Anthony J. A. , Las Guy , Yaniv Gal , Hajnóczky György , Shirihai Orian S.
Published: May 2010

Studies in various types of cells find that, on average, each mitochondrion becomes involved in a fusion event every 15 min, depending on the cell type. As most contact events do not result in mitochondrial fusion, it is expected that properties of the individual mitochondrion determine the likelihood of a fusion event. However, apart from membrane potential, the properties that influence the likelihood of entering a fusion event are not known. Here, we tag and track individual mitochondria in H9c2, INS1, and primary β-cells and determine the biophysical properties that increase the likelihood of a fusion event. We found that the probability for fusion is independent of contact duration and organelle dimensions, but it is influenced by organelle motility. Furthermore, the history of a previous fusion event of the individual mitochondrion influenced both the likelihood for a subsequent fusion event, as well as the site on the mitochondrion at which the fusion occurred. These observations unravel the specific properties that distinguish mitochondria that will enter fusion events from the ones that will not. Altogether, these properties may help to elucidate the molecular mechanisms that regulate fusion at the level of the single mitochondrion.
Is there evidence for nonthermal modulation of whole body heat loss during intermittent exercise?
Authors: Kenny Glen P. , Gagnon Daniel
Published: May 2010

This study compared the effect of active, passive, and inactive recoveries on whole body evaporative and dry heat loss responses during intermittent exercise at an air temperature of 30°C and a relative humidity of 20%. Nine males performed three 15-min bouts of upright seated cycling at a fixed external workload of 150 W. The exercise bouts were separated by three 15-min recoveries during which participants 1) performed loadless pedaling (active recovery), 2) had their lower limbs passively compressed with inflatable sleeves (passive recovery), or 3) remained upright seated on the cycle ergometer (inactive recovery). Combined direct and indirect calorimetry was employed to measure rates of whole body evaporative heat loss (EHL) and metabolic heat production (M-W). Mean body temperature (Tb) was calculated from esophageal and mean skin temperatures, and mean arterial pressure (MAP) was measured continuously. Active and passive recoveries both reversed the reduction in MAP associated with inactive recovery ( P ≤ 0.05). This response was paralleled by greater levels of EHL during active (207 ± 53 W) and passive recoveries (203 ± 55 W) compared with the inactive condition (168 ± 53 W, P ≤ 0.05). However, the greater rate of EHL during active recovery was paralleled by a greater M-W (194 ± 16 W) compared with inactive recovery (149 ± 27 W, P ≤ 0.001). In contrast, M-W during passive recovery (139 ± 20 W) was not significantly different from the inactive condition ( P = 0.468). Furthermore, there were no differences in Tb between inactive and passive conditions during the recovery periods ( P = 0.820). As such, passive recovery resulted in greater levels of EHL for a given change in Tb compared with inactive recovery ( P ≤ 0.05). These results strongly suggest that the progressive increase in core temperature during successive exercise/rest cycles is primarily the result of a baroreflex-mediated attenuation of postexercise whole body evaporative heat loss.
Coding Observed Motor Acts: Different Organizational Principles in the Parietal and Premotor Cortex of Humans
Authors: Jastorff Jan , Begliomini Chiara , Fabbri-Destro Maddalena , Rizzolatti Giacomo , Orban Guy A.
Published: May 2010

Understanding actions of conspecifics is a fundamental social ability depending largely on the activation of a parieto-frontal network. Using functional MRI (fMRI), we studied how goal-directed movements (i.e., motor acts) performed by others are coded within this network. In the first experiment, we presented volunteers with video clips showing four different motor acts (dragging, dropping, grasping, and pushing) performed with different effectors (foot, hand, and mouth). We found that the coding of observed motor acts differed between premotor and parietal cortex. In the premotor cortex, they clustered according to the effector used, and in the inferior parietal lobule (IPL), they clustered according to the type of the observed motor act, regardless of the effector. Two subsequent experiments in which we directly contrasted these four motor acts indicated that, in IPL, the observed motor acts are coded according to the relationship between agent and object: Movements bringing the object toward the agent (grasping and dragging) activate a site corresponding approximately to the ventral part of the putative human AIP (phAIP), whereas movements moving the object away from the agent (pushing and dropping) are clustered dorsally within this area. These data provide indications that the phAIP region plays a role in categorizing motor acts according to their behavioral significance. In addition, our results suggest that in the case of motor acts typically done with the hand, the representations of such acts in phAIP are used as templates for coding motor acts executed with other effectors.
Reward, Addiction, and Emotion Regulation Systems Associated With Rejection in Love
Authors: Fisher Helen E. , Brown Lucy L. , Aron Arthur , Strong Greg , Mashek Debra
Published: May 2010

Romantic rejection causes a profound sense of loss and negative affect. It can induce clinical depression and in extreme cases lead to suicide and/or homicide. To begin to identify the neural systems associated with this natural loss state, we used functional magnetic resonance imaging to study 10 women and 5 men who had recently been rejected by a partner but reported they were still intensely “in love.” Participants alternately viewed a photograph of their rejecting beloved and a photograph of a familiar, individual, interspersed with a distraction-attention task. Their responses while looking at their rejecter included love, despair, good, and bad memories, and wondering why this happened. Activation specific to the image of the beloved occurred in areas associated with gains and losses, craving and emotion regulation and included the ventral tegmental area (VTA) bilaterally, ventral striatum, medial and lateral orbitofrontal/prefrontal cortex, and cingulate gyrus. Compared with data from happily-in-love individuals, the regional VTA activation suggests that mesolimbic reward/survival systems are involved in romantic passion regardless of whether one is happily or unhappily in love. Forebrain activations associated with motivational relevance, gain/loss, cocaine craving, addiction, and emotion regulation suggest that higher-order systems subject to experience and learning also may mediate the rejection reaction. The results show activation of reward systems, previously identified by monetary stimuli, in a natural, endogenous, negative emotion state. Activation of areas involved in cocaine addiction may help explain the obsessive behaviors associated with rejection in love.
Polyethylene Glycol Rapidly Restores Axonal Integrity and Improves the Rate of Motor Behavior Recovery After Sciatic Nerve Crush Injury
Authors: Britt Joshua M. , Kane Jacqueline R. , Spaeth Christopher S. , Zuzek Aleksej , Robinson Garrett L. , Gbanaglo Melengor Y. , Estler Cody J. , Boydston Elaine A. , Schallert Timothy , Bittner George D.
Published: May 2010

The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in vivo. We now report that PEG-fusion not only reestablishes the integrity of crush-severed rat sciatic axons as measured by the restored conduction of compound action potentials (CAPs) and the intraaxonal diffusion of fluorescent dye across the lesion site, but also produces more rapid recovery of appropriate hindlimb motor behaviors. Improvement in recovery occurred during the first few postoperative weeks for the foot fault (FF) asymmetry test and between week 2 and week 3 for the Sciatic Functional Index (SFI) based on analysis of footprints. That is, the FF test was the more sensitive indicator of early behavioral recovery, showing significant postoperative improvement of motor behavior in PEG-treated animals at 24–48 h. In contrast, the SFI more sensitively measured longer-term postoperative behavioral recovery and deficits at 4–8 wk, perhaps reflecting the development of fine (distal) motor control. These and other data show that PEG-fusion not only rapidly restores physiological and morphological axonal continuity, but also more quickly improves behavioral recovery.
Taste-Specific Cell Assemblies in a Biologically Informed Model of the Nucleus of the Solitary Tract
Authors: Rosen Andrew M. , Sichtig Heike , Schaffer J. David , Di Lorenzo Patricia M.
Published: May 2010

Although the cellular organization of many primary sensory nuclei has been well characterized, questions remain about the functional architecture of the first central relay for gustation, the rostral nucleus of the solitary tract (NTS). Here we used electrophysiological data recorded from single cells in the NTS to inform a network model of taste processing. Previous studies showed that electrical stimulation of the chorda tympani (CT) nerve initiates two types of inhibitory influences with different time courses in separate groups of NTS cells. Each type of inhibition targeted cells with distinct taste response properties. Further analyses of these data identified three NTS cell types differentiated by their latency of evoked response, time course of CT evoked inhibition, and degree of selectivity across taste qualities. Based on these results, we designed a model of the NTS consisting of discrete, reciprocally connected, stimulus-specific “cell” assemblies. Input to the network of integrate-and-fire model neurons was based on electrophysiological recordings from the CT nerve. Following successful simulation of paired-pulse CT stimulation, the network was tested for its ability to discriminate between two “taste” stimuli. Network dynamics of the model produced biologically plausible responses from each unit type and enhanced discrimination between taste qualities. We propose that an interactive network of taste quality specific cell assemblies, similar to our model, may account for the coherence in across-neuron patterns of NTS responses between similar tastants.
Subthreshold Membrane Conductances Enhance Directional Selectivity in Vertebrate Sensory Neurons
Authors: Chacron Maurice J. , Fortune Eric S.
Published: May 2010

Directional selectivity, in which neurons respond preferentially to one “preferred” direction of movement over the opposite “null” direction, is a critical computation that is found in the central nervous systems of many animals. Such responses are generated using two mechanisms: spatiotemporal convergence via pathways that differ in the timing of information from different locations on the receptor array and the nonlinear integration of this information. Previous studies have showed that various mechanisms may act as nonlinear integrators by suppressing the response in the null direction. Here we show, through a combination of mathematical modeling and in vivo intracellular recordings, that subthreshold membrane conductances can act as a nonlinear integrator by increasing the response in the preferred direction of motion only, thereby enhancing the directional bias. Such subthreshold conductances are ubiquitous in the CNS and therefore may be used in a wide array of computations that involve the enhancement of an existing bias arising from differential spatiotemporal filtering.
EREM: Parameter Estimation and Ancestral Reconstruction by Expectation-Maximization Algorithm for a Probabilistic Model of Genomic Binary Characters Evolution
Authors: Carmel Liran , Wolf Yuri I. , Rogozin Igor B. , Koonin Eugene V.
Published: May 2010

Evolutionary binary characters are features of species or genes, indicating the absence (value zero) or presence (value one) of some property. Examples include eukaryotic gene architecture (the presence or absence of an intron in a particular locus), gene content, and morphological characters. In many studies, the acquisition of such binary characters is assumed to represent a rare evolutionary event, and consequently, their evolution is analyzed using various flavors of parsimony. However, when gain and loss of the character are not rare enough, a probabilistic analysis becomes essential. Here, we present a comprehensive probabilistic model to describe the evolution of binary characters on a bifurcating phylogenetic tree. A fast software tool, EREM, is provided, using maximum likelihood to estimate the parameters of the model and to reconstruct ancestral states (presence and absence in internal nodes) and events (gain and loss events along branches).
Adaptive Representations for Improving Evolvability, Parameter Control, and Parallelization of Gene Expression Programming
Authors: Browne Nigel P. A. , dos Santos Marcus V.
Published: May 2010

Gene Expression Programming (GEP) is a genetic algorithm that evolves linear chromosomes encoding nonlinear (tree-like) structures. In the original GEP algorithm, the genome size is problem specific and is determined through trial and error. In this work, a method for adaptive control of the genome size is presented. The approach introduces mutation, transposition, and recombination operators that enable a population of heterogeneously structured chromosomes, something the original GEP algorithm does not support. This permits crossbreeding between normally incompatible individuals, speciation within a population, increases the evolvability of the representations, and enhances parallel GEP. To test our approach, an assortment of problems were used, including symbolic regression, classification, and parameter optimization. Our experimental results show that our approach provides a solution for the problem of self-adaptive control of the genome size of GEP's representation.
Fabrication of Dye-Sensitized Solar Cells with a 3D Nanostructured Electrode
Authors: Chen Guo-Yang , Lee Ming-Way , Wang Gou-Jen
Published: May 2010

A novel Dye-Sensitized Solar Cell (DSSC) scheme for better solar conversion efficiency is proposed. The distinctive characteristic of this novel scheme is that the conventional thin film electrode is replaced by a 3D nanostructured indium tin oxide (ITO) electrode, which was fabricated using RF magnetron sputtering with an anodic aluminum oxide (AAO) template. The template was prepared by immersing the barrier-layer side of an AAO film into a 30 wt% phosphoric acid solution to produce a contrasting surface. RF magnetron sputtering was then used to deposit a 3D nanostructured ITO thin film on the template. The crystallinity and conductivity of the 3D ITO films were further enhanced by annealing. Titanium dioxide nanoparticles were electrophoretically deposited on the 3D ITO film after which the proposed DSSC was formed by filling vacant spaces in the 3D nanostructured ITO electrode with dye. The measured solar conversion efficiency of the device was 0.125%. It presents a 5-fold improvement over that of conventional spin-coatedTiO2film electrode DSSCs.
IL-17B Can Impact on Endothelial Cellular Traits Linked to Tumour Angiogenesis
Authors: Sanders Andrew J. , Guo Xiaoxia , Mason Malcolm D. , Jiang Wen G.
Published: May 2010

IL-17B is a member of the IL-17 cytokine family which have been implicated in inflammatory response and autoimmune diseases such as rheumatoid arthritis. The founding member of this family, IL-17 (or IL-17A), has also been implicated in promoting tumour angiogenesis through the induction of other proangiogenic factors. Here we examine the potential of recombinant human IL-17B to contribute to the angiogenic process. In vitro rhIL-17B was able to inhibit HECV endothelial cell-matrix adhesion and cellular migration and also, at higher concentrations, could substantially reduce tubule formation compared to untreated HECV cells in a Matrigel tubule formation assay. This data suggests that IL-17B may act in an antiangiogenic manner.
Synthesis of Silver Nanoparticles by Precipitation in Bicontinuous Microemulsions
Authors: Reyes Pamela Y. , Espinoza Jesús A. , Treviño María E. , Saade Hened , López Raúl G.
Published: May 2010

Silver nanoparticles precipitation was carried out at 70∘C in bicontinuous microemulsions stabilized with a mixture of surfactants sodium bis (2‐ethylhexyl) sulfosuccinate/sodium dodecyl sulfate (2/1, w/w) containing an aqueous solution of 0.5 M silver nitrate and toluene as organic phase. Various concentrations of aqueous solution of sodium borohydride (precipitating agent) and their dosing times on microemulsions were studied. Regardless of dosing time, higher and medium concentrations of precipitating agent promoted the formation of worm‐like nanostructures, while the lowest concentration allowed to obtain a mixture of isolated silver nanoparticles (mean diameter ≈3 nm) and worm‐like nanostructures. Experimental yields much higher than those typical in precipitation of silver nanoparticles in reverse microemulsions were obtained. An explanation for formation of worm‐like nanostructures based on the development of local zones inside the microemulsions channels with high particle concentrations was proposed.
Can Lactase Persistence Genotype Be Used to Reassess the Relationship between Renal Cell Carcinoma and Milk Drinking? Potentials and Problems in the Application of Mendelian Randomization
Authors: Timpson Nicholas J. , Brennan Paul , Gaborieau Valérie , Moore Lee , Zaridze David , Matveev Vsevolod , Szeszenia-Dabrowska Neonilia , Lissowska Jolanta , Mates Dana , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Chow Wong-Ho , Rothman Nathaniel , Boffetta Paolo , Harbord Roger M. , Davey Smith George
Published: May 2010

Background: Increased risk of renal cell carcinoma (RCC) with milk consumption has been reported from observational studies. Whether this represents a causal association or is a result of confounding or bias is unclear. We assessed the potential for using genetic variation in lactase persistence as a tool for the study of this relationship.

Methods: Using a large, hospital-based case-control study, we used observational, phenotypic, and genetic data to determine whether the MCM6 −13910 C/T(rs4988235) variant may be used as a nonconfounded and unbiased marker for milk consumption.

Results: Consumption of milk during adulthood was associated with increased risk of RCC [odds ratio (OR), 1.35; 95% confidence interval (95% CI), 1.03-1.76; P = 0.03]. Among controls, consumption of milk was associated with the lactase persistence genotype at rs4988235 (OR, 2.39; 95% CI, 1.81-3.15; P = 6.9 × 10−10); however, the same genotype was not associated with RCC (OR, 1.01; 95% CI, 0.83-1.22; P = 0.9). In controls, milk consumption was associated with confounding factors, including smoking and educational attainment, whereas genotypes at rs4988235 showed negligible association with confounding factors.

Conclusion: The absence of an association between the MCM6 genotype and RCC suggests that observational associations between milk consumption and RCC may be due to confounding or bias.

Impact: Although these data suggest that associations between milk consumption and RCC may be spurious, if the association between genotype and behavioral exposure is weak, then the power of this test may be low. The nature of intermediate risk factor instrumentation is an important consideration in the undertaking and interpretation of this type of causal analysis experiment. Cancer Epidemiol Biomarkers Prev; 19(5); 1341–8. ©2010 AACR.
Collagen XXIII: A Potential Biomarker for the Detection of Primary and Recurrent Non–Small Cell Lung Cancer
Authors: Spivey Kristin A. , Banyard Jacqueline , Solis Luisa M. , Wistuba Ignacio I. , Barletta Justine A. , Gandhi Leena , Feldman Henry A. , Rodig Scott J. , Chirieac Lucian R. , Zetter Bruce R.
Published: May 2010

Background: Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer. The purpose of this study was to determine the protein expression of collagen XXIII in tumor tissues from a variety of cancers and to assess the utility of collagen XXIII as a biomarker for non–small cell lung cancer (NSCLC).

Methods: A multicancer tissue microarray was used for the immunohistochemical examination of collagen XXIII protein expression in a variety of cancers. Subsequently, collagen XXIII expression was analyzed in three separate cohorts using tissue microarrays with representative tumor and control lung tissues from NSCLC patients. In addition, NSCLC patient urine samples were analyzed for the presence of collagen XXIII through Western blot.

Results: Collagen XXIII was present in tissue samples from a variety of cancers. Within lung cancer tissues, collagen XXIII staining was enriched in NSCLC subtypes. Collagen XXIII was present in 294 of 333 (88%) lung adenocarcinomas and 97 of 133 (73%) squamous cell carcinomas. In urine, collagen XXIII was present in 23 of 29 (79%) NSCLC patient samples but only in 15 of 54 (28%) control samples. High collagen XXIII staining intensity correlated with shorter recurrence-free survival in NSCLC patients.

Conclusions: We show the capability of collagen XXIII as a tissue and urinary biomarker for NSCLC, in which positivity in tissue or urine significantly correlates with the presence of NSCLC and high staining intensity is a significant recurrence predictor.

Impact: Inclusion of collagen XXIII in a tissue- or urine-based cancer biomarker panel could inform NSCLC patient treatment decisions. Cancer Epidemiol Biomarkers Prev; 19(5); 1362–72. ©2010 AACR.
Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2
Authors: Prokunina-Olsson Ludmila , Fu Yi-Ping , Tang Wei , Jacobs Kevin B. , Hayes Richard B. , Kraft Peter , Berndt Sonja I. , Wacholder Sholom , Yu Kai , Hutchinson Amy , Spencer Feigelson Heather , Thun Michael J. , Diver W. Ryan , Albanes Demetrius , Virtamo Jarmo , Weinstein Stephanie , Schumacher Fredrick R. , Cancel-Tassin Geraldine , Cussenot Olivier , Valeri Antoine , Andriole Gerald L. , Crawford E. David , Haiman Christopher A. , Henderson Brian E. , Kolonel Laurence , Le Marchand Loic , Siddiq Afshan , Riboli Elio , Travis Ruth , Kaaks Rudolf , Isaacs William B. , Isaacs Sarah D. , Grönberg Henrik , Wiklund Fredrik , Xu Jianfeng , Vatten Lars J. , Hveem Kristian , Kumle Merethe , Tucker Margaret , Hoover Robert N. , Fraumeni Joseph F. , Hunter David J. , Thomas Gilles , Chatterjee Nilanjan , Chanock Stephen J. , Yeager Meredith
Published: May 2010

Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 × 10−6), with a suggestion of stronger association with aggressive disease (P = 1.2 × 10−7).

Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.

Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 × 10−11; ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 × 10−4 for aggressive cancer, n = 4,597; P = 3.25 × 10−8 for nonaggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657).

Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry.

Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349–55. ©2010 AACR.
Perineal Use of Talcum Powder and Endometrial Cancer Risk
Authors: Karageorgi Stalo , Gates Margaret A. , Hankinson Susan E. , De Vivo Immaculata
Published: May 2010

Background: Several studies have reported a positive association between perineal use of talcum powder among adult women and ovarian cancer risk. However, the relationship between talcum powder use and other gynecologic malignancies such as endometrial cancer has not been examined, and little information is available on nonhormonal risk factors for endometrial cancer.

Methods: Perineal use of talcum powder was assessed in 1982 in the Nurses' Health Study. Approximately 40% of women who responded to the questions about perineal use of talcum powder reported ever use. Cox proportional hazards models were used to estimate the incidence rate ratio of endometrial cancer and 95% confidence interval (CI), adjusted for body mass index and other potential confounders. We evaluated the relationship among all women and stratified by menopausal status.

Results: Our analysis included 66,028 women with 599 incident cases of invasive endometrial adenocarcinoma diagnosed between 1982 and 2004. Although no association was observed overall, the association varied by menopausal status (P interaction = 0.02) and a positive association was observed among postmenopausal women; ever use of talcum powder was associated with a 21% increase in risk of endometrial cancer (95% CI, 1.02-1.44), whereas regular use (at least once a week) was associated with a 24% increase in risk (95% CI, 1.03-1.48). In addition, we observed a borderline increase in risk with increasing frequency of use (P trend = 0.04).

Conclusions: Our results suggest that perineal talcum powder use increases the risk of endometrial cancer, particularly among postmenopausal women.

Impact: Future and larger studies are needed to confirm this association and investigate potential mechanisms. Cancer Epidemiol Biomarkers Prev; 19(5); 1269–75. ©2010 AACR.
Polymorphisms in the TOX3/LOC643714 Locus and Risk of Breast Cancer in African-American Women
Authors: Ruiz-Narváez Edward A. , Rosenberg Lynn , Cozier Yvette C. , Cupples L. Adrienne , Adams-Campbell Lucile L. , Palmer Julie R.
Published: May 2010

Background: The rs3803662 single nucleotide polymorphism (SNP) in the TOX3/LOC643714 region was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry and has been replicated in other populations of European ancestry. The position of the causal variant tagged by the rs3803662 marker is still unknown. In fact, because the rs3803662 polymorphism is located between the TOX3 and the LOC643714 loci, it is unclear which gene is the one causally related to the risk of breast cancer. Because linkage disequilibrium blocks are smaller in populations of African ancestry, fine-mapping in African ancestry samples might be an effective approach to narrowing the position of the causal variant(s) in the TOX3/LOC643714 locus.

Methods: We evaluated a total of 60 tagging SNPs throughout the TOX3/LOC643714 region in a nested case-control study of breast cancer within the Black Women's Health Study, which included 906 cases and 1,111 controls.

Results: No significant association was found for the rs3803662 SNP. However, four other SNPs (rs3104746, rs3112562, rs3104793, and rs8046994), all of them located in the LOC643714 gene, were associated with risk of breast cancer. The strongest association was observed for rs3104746: each copy of the A-rs3104746 allele was associated with a 23% higher risk of breast cancer (odds ratios, 1.23; 95% confidence intervals, 1.05-1.44; P = 0.009).

Conclusions: Our results confirm the association observed in genome-wide association studies of European ancestry populations.

Impact: The results narrow the locus to a smaller linkage disequilibrium block in the LOC643714 gene. Cancer Epidemiol Biomarkers Prev; 19(5); 1320–7. ©2010 AACR.
Folate Intake along with Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase in Patients with Advanced Gastric Cancer
Authors: Shitara Kohei , Muro Kei , Ito Seiji , Sawaki Akira , Tajika Masahiro , Kawai Hiroki , Yokota Tomoya , Takahari Daisuke , Shibata Takashi , Ura Takashi , Ito Hidemi , Hosono Satoyo , Kawase Takakazu , Watanabe Miki , Tajima Kazuo , Yatabe Yasushi , Tanaka Hideo , Matsuo Keitaro
Published: May 2010

Background: A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. Furthermore, there are several reports that evaluated genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) and efficacy of FU. However, to our knowledge, there are no reports that evaluate simultaneously the effects of folate intake and genetic polymorphisms on clinical outcome of gastric cancer patients.

Methods: We retrospectively analyzed the survival impact of estimated folate intake by a food frequency questionnaire and MTHFR and TYMS polymorphisms in 132 patients with advanced gastric cancer who were treated with first-line FU-based chemotherapy.

Results: Median overall survival was 11.3 months (95% confidence interval, 9.4-13.4 mo) and median progression-free survival was 5.2 months (95% confidence interval, 4.1-6.3 mo). Patients with folate intake of >260 μg/day (n = 88) showed longer overall survival compared with low folate intake (n = 44; overall survival, 12.2 versus 8.4 mo). In a multivariate Cox model, patients who had folate intake of >260 μg/day, MTHFR 677 TT polymorphism, and TYMS-3′ untranslated region 6-bp insertion were associated with better survival. Similar tendency was observed in progression-free survival. No interaction was observed between folate intake and favorable genotypes.

Conclusion: Folate intake and genetic polymorphisms of MTHFR and TYMS were associated with better clinical outcome by FU-based chemotherapy in advanced gastric cancer.

Impact: Our results suggested folate intake and folate-related genetic polymorphisms may play an important role in efficacy of FU-based chemotherapy in advanced gastric cancer. Cancer Epidemiol Biomarkers Prev; 19(5); 1311–9. ©2010 AACR.
Elevated Levels of Volatile Organic Carcinogen and Toxicant Biomarkers in Chinese Women Who Regularly Cook at Home
Authors: Hecht Stephen S. , Seow Adeline , Wang Mingyao , Wang Renwei , Meng Lei , Koh Woon-Puay , Carmella Steven G. , Chen Menglan , Han Shaomei , Yu Mimi C. , Yuan Jian-Min
Published: May 2010

Background: Epidemiologic studies associate lung cancer in nonsmoking Chinese women with Chinese-style wok cooking. Our goal was to quantify carcinogen and toxicant biomarkers in Chinese women who reported regularly doing home cooking compared with women randomly selected from the Singapore Chinese Health Study as controls.

Methods: Biomarkers were quantified by high-performance liquid chromatography–mass spectrometry, high-performance liquid chromatography with fluorescence detection, and gas chromatography–mass spectrometry.

Results: Compared with controls, women who engaged in regular home cooking had significantly higher levels of mercapturic acids of acrolein {geometric mean, 1,959 pmol/mg creatinine [95% confidence interval (95% CI), 1,554-2,467] versus 1,370 (95% CI, 1,077-1,742); P = 0.038}, crotonaldehyde [geometric mean, 232 pmol/mg creatinine (95% CI, 193-277) versus 142 (95% CI, 118-171); P = 0.0004], and benzene [geometric mean, 0.58 pmol/mg creatinine (95% CI, 0.44-0.78) versus 0.18 (95% CI, 0.14-0.24); P < 0.0001]. No significant differences were found in levels of mercapturic acids of 1,3-butadiene, metabolites of pyrene and phenanthrene, or acetaldehyde-leukocyte DNA adduct levels between the groups. Levels of the ethylene oxide mercapturic acid were significantly higher in the controls.

Conclusions: The higher levels of the mercapturic acid of benzene, a multiorgan carcinogen, in the women who cooked are particularly notable. Overall, the results showing increased exposure to the volatile toxicants and carcinogens acrolein, crotonaldehyde, and benzene in Chinese women who regularly cook provide a plausible lead for further investigating the role of volatile compounds generated during high-temperature cooking with oils as causes of lung cancer.

Impact: A new direction for research on lung cancer etiology is suggested. Cancer Epidemiol Biomarkers Prev; 19(5); 1185–92. ©2010 AACR.
Interaction between Cigarette Smoking and Hepatitis B and C Virus Infection on the Risk of Liver Cancer: A Meta-analysis
Authors: Chuang Shu-Chun , Lee Yuan-Chin Amy , Hashibe Mia , Dai Min , Zheng Tongzhang , Boffetta Paolo
Published: May 2010

Introduction: Chronic infection with hepatitis B (HBV) and C viruses (HCV) as well as cigarette smoking are established risk factors of hepatocellular carcinoma (HCC), but it is unclear whether an interaction exists between these factors in causing hepatocellular carcinogenesis. We conducted a meta-analysis to evaluate the interaction of HBV and HCV infection and cigarette smoking on the risk of HCC.

Methods: We systematically searched the PUBMED and the China National Knowledge Infrastructure databases. A total of 16 eligible publications were identified. Cigarette smoking and chronic HBV and HCV infections were dichotomized into present or absent. Additive (S) and multiplicative interaction indexes (V) between smoking and each of the two infections and their 95% confidence intervals (95% CI) were calculated for each study and then combined in a meta-analysis.

Results: We found a more than additive interaction between HBV infection and cigarette smoking (S = 1.44; 95% CI, 1.00-2.06; nine studies) and a more than multiplicative interaction (V = 1.60; 95% CI, 1.16-2.20; six studies) between HCV infection and cigarette smoking. No publication bias was detected.

Conclusion: Smoking seems to interact with both HBV and HCV in determining HCC risk. A pooled analysis of individual subject data, with appropriate adjustment with other risk factors, is warranted to confirm these results.

Impact: The results of this study imply the evidence of a synergistic effect between smoking and HBV or HCV infection on the risk of HCC. Thus, chronic carriers of HBV or HCV are recommended to avoid smoking. Cancer Epidemiol Biomarkers Prev; 19(5); 1261–8. ©2010 AACR.
Questionnaire Items to Assess Skin Color and Erythemal Sensitivity: Reliability, Validity, and “the Dark Shift”
Authors: Reeder Anthony I. , Hammond Vanessa A. , Gray Andrew R.
Published: May 2010

Background: Skin pigmentation is a key factor for UV radiation exposure related cancers. To appropriately target cancer control activities related to this exposure and for better representation in epidemiologic studies, a valid and reliable assessment of skin color is required.

Methods: The validity and reliability of two self-report measures were assessed: skin color and erythemal sensitivity. A sample of 289 university students categorized their unexposed skin color and photosensitivity via a questionnaire. Skin color was also measured by spectrophotometer. After 7 days, participants repeated the self-report assessment.

Results: Significant correlations were found for both self-report items with objective measures, indicating that these items may be valid assessment tools (color: Spearman's ρ = −0.75, P < 0.001; photosensitivity: Spearman's ρ = −0.64, P < 0.001). No sex differences in validity were evident. Stronger correlations were found among those of European than those of non-European ethnicity (color: Spearman's ρ = −0.78 versus −0.59, bootstrap P = 0.007; photosensitivity: Spearman's ρ = −0.63 versus −0.28, bootstrap P = 0.001). Strong biases toward overestimation of skin pigmentation were evident, ranging from 36% in the self-identified fair skin group to 77% in the medium skin color group. Intrarater reliability of the questionnaire items was high (color: k = 0.78, P < 0.001; photosensitivity: k = 0.77, P < 0.001).

Conclusions: Study findings suggest that self-report may be a valid measurement strategy when assessing skin type, but there is a bias toward overestimation of skin color and, potentially, UV radiation resilience.

Impact: This bias has the potential to undermine the effectiveness of skin cancer prevention efforts and needs to be addressed in health promotion programs. Cancer Epidemiol Biomarkers Prev; 19(5); 1167–73. ©2010 AACR.
Estimation of Nicotine Dose after Low-level Exposure Using Plasma and Urine Nicotine Metabolites
Authors: Benowitz Neal L. , Dains Katherine M. , Dempsey Delia , Yu Lisa , Jacob Peyton
Published: May 2010

Background: We sought to determine the optimal plasma and urine nicotine metabolites, alone or in combination, to estimate the systemic dose of nicotine after low-level exposure.

Methods: We dosed 36 nonsmokers with 100, 200, or 400 μg p.o. of deuterium-labeled nicotine (doses similar to exposure to secondhand smoke) daily for 5 days and then measured plasma and urine nicotine metabolites at various intervals over 24 hours.

Results: The strongest correlations with nicotine dose were seen for the sum of four (cotinine + cotinine-glucuronide + trans-3′-hydroxycotinine + 3HC-glucuronide) or six (including also nicotine + nicotine-glucuronide) of the major nicotine metabolites in 24-hour urine collection (r = 0.96), with lesser correlations for these metabolites using spot urines corrected for creatinine at various times of day (r = 0.72-0.80). The sum of plasma cotinine + trans-3′-hydroxycotine was more highly correlated with nicotine dose than plasma cotinine alone (r = 0.82 versus 0.75).

Conclusions: Our results provide guidance for the selection of biomarkers to estimate the dose of nicotine taken in low-level (secondhand smoke) tobacco exposure.

Impact: This is probably relevant to active smoking as well. Cancer Epidemiol Biomarkers Prev; 19(5); 1160–6. ©2010 AACR.