bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigating Transverse Joint Faulting in Jointed Concrete Pavement with Polyurethane Foam
Authors: Gaspard Kevin , Zhang Zhongjie
Published: November 2010

A case study was conducted to assess the effectiveness of reducing transverse faulting on jointed concrete pavement with polyurethane foam (PF) on a principal arterial roadway with an average daily traffic of 15,800 with 20% trucks. The PF fault correction process entailed reducing faults to approximately 0.25 in. by saw-cutting the full depth through the joints and lifting the slabs with PF. A sampling plan was established: the entire project was measured for faulting and roughness by a high-speed profiler before and after the PF fault correction process. Three test sections with 10 slabs each were assessed with a falling weight deflectometer, ARRB walking profiler, and manual fault measurements. Seventeen cores were taken at various locations to obtain in-place PF samples. Statistical hypothesis testing was conducted to compare the before-and-after treatment effect of the PF process. Approximately 18% improvement in ride quality and 79% improvement in fault reduction were realized by the PF fault correction process. Unfortunately, the PF process severely affected load transfer efficiency, with a 43% increase in joints having poor load transfer and a 27% increase in joints needing load transfer improvement. It is reasonable to assume that these problems were caused primarily by saw-cutting through the joints and not by PF itself. Void potentials were increased slightly (8%) by the process.
Behavior of Tied Multiple-Lane Portland Cement Concrete Pavement
Authors: Ha Soojun , Choi Seongcheol , Won Moon C.
Published: November 2010

Tie bars are used at longitudinal construction joints (LCJs) in portland cement concrete (PCC) pavement primarily to keep lanes from separating. As more lanes are tied together because of ever-increasing traffic volume, concerns about the potential for longitudinal cracking have led to the use of dowel bars at LCJs. However, a survey of a number of state highway agencies (SHAs) revealed that few of them have guidelines and design standards for the use of dowel bars at LCJs and that no in-depth studies conducted in this area have been identified. The effects of multiple lane ties and dowel bar placements in PCC pavements are analyzed in this paper to provide basic information on whether dowel bars are really needed, and if they are, where they should be placed and what their advantages and disadvantages are. Field testing verified that the longitudinal cracking potential is greater as slab thickness and lane width increase. The effects of multiple lane ties and dowel bar placements at LCJs are evaluated with numerical analysis. Placing dowel bars in lieu of tie bars reduces the longitudinal cracking potential, and the effectiveness of using dowel bars is enhanced when they are applied to thicker and wider pavements. However, the use of dowel bars could result in increased potential for lane separations.
Near-Surface Pavement Failure under Multiaxial Stress State in Thick Asphalt Pavement
Authors: Wang Hao , Al-Qadi Imad L.
Published: November 2010

The failure of pavement near its surface (rutting and cracking) is a complex phenomenon affected by vehicular loading and pavement structure. This paper documents the investigation of near-surface failure in thick asphalt pavement by using a developed three-dimensional (3-D) finite element (FE) model and Mohr–Coulomb failure criterion. The FE model incorporates measured 3-D tire–pavement contact stresses, hot-mix asphalt (HMA) linear viscoelasticity, continuously moving load, and implicit dynamic analysis. The multiaxial stress states (normal and shear stress) near the pavement surface under measured stresses from tire contact and from moving wheel load are presented. The failure potential of pavement near the surface was evaluated by comparing the multiaxial stress states predicted from the FE model to the Mohr–Coulomb failure criterion. The authors suggest that the cracking could start at the pavement's surface within the area between dual tires. This paper presents several conclusions about surface-initiated cracking potential: (a) it increases as the temperature increases; (b) at high temperatures, the shear-induced surface cracking could start from some distance below the pavement surface in conjunction with the distortional deformation; (c) compared with the 3-D tire contact stress, the uniform contact stress distribution underestimates the pavement failure potential near the surface, especially at high temperatures; (d) the negative temperature gradient in the HMA layer induces a greater failure potential at the pavement near-surface compared with the constant average temperature case; and (e) the debonding under the surface layer significantly increases the shear stress at relatively low normal stress and leads to premature failure around the interface compared with the full bonding case.
Analysis of Virginia-Specific Traffic Data for Use with Mechanistic–Empirical Pavement Design Guide
Authors: Smith Bryan C. , Diefenderfer Brian K.
Published: November 2010

This study developed traffic inputs for use with the Guide for the Mechanistic–Empirical Design of New and Rehabilitated Pavement Structures (MEPDG) in Virginia and sought to determine whether the predicted distresses showed differences between site-specific and default traffic inputs for flexible pavements. The predicted distresses based on site-specific inputs from eight Interstate weigh-in-motion sites in Virginia were compared with predicted distresses by means of MEPDG default traffic inputs. These comparisons were performed with the use of a normalized-difference statistic for each site-specific traffic input and the coefficient of variation for each pavement distress model. In addition, the practical significance was considered from the difference in the predicted time to failure between site-specific and default traffic inputs. The analysis showed that the effect of the site-specific traffic inputs was generally not statistically significant when the uncertainty of the distress models was considered. However, the site-specific axle load spectra inputs showed a practically significant increase in the predicted time to failure compared with the default traffic inputs. From this study, it is recommended that users of the MEPDG consider collecting site-specific axle load spectra data for analysis of flexible pavements. In addition, analysis of flexible pavements may be performed by using the default inputs for the remaining traffic parameters. Given the mixed conclusions in previous studies, it may be necessary for each user or agency to conduct a similar evaluation for its local combination of traffic, materials, climate, and typical pavement structures.
Longitudinal Joint Data Collection Efforts in Virginia between 2005 and 2009
Authors: Appea Alexander K. , Clark Trenton
Published: November 2010

Premature deterioration of asphalt concrete at longitudinal joints has been a problem for many transportation agencies for years. The primary cause of this deterioration is the lack of in-place density. To address this issue, the Virginia Department of Transportation (VDOT) and the Virginia Asphalt Association (VAA) formed an alliance to seek a solution to the problem. Instead of developing a new specification for longitudinal joint density and potentially increasing construction costs, the alliance developed a communication and training plan focused on proper joint compaction. This plan included a joint construction memorandum and a field training program. During the implementation year (2005), data collection revealed improved density values at the joints. In subsequent years (2006 and 2007) the joint densities began to decline. Therefore VDOT and VAA emphasized adherence to proper joint construction during the 2009 paving season. Results collected through July 2009 indicated a significant improvement in joint densities. A substantial improvement was noted in the SM-12.5 surface mixes. Average differences of less than 2% between mat and joint densities for the 12.5-mm mixes were obtained. Statistical results from analysis of variance and F-tests also confirmed this trend.
Comparison of Moduli of Kansas Superpave Asphalt Mixes
Authors: Gedafa Daba S. , Hossain Mustaque , Romanoschi Stefan A. , Gisi Andrew J.
Published: November 2010

Currently, hot-mix asphalt (HMA) mixture design and pavement structural design are not fully integrated, although Superpave® asphalt mixture design is somewhat project specific. The objective of this study was to compare elastic moduli assumed during structural design of pavements with the backcalculated moduli of HMA layers obtained from the falling weight deflectometer (FWD) tests and the dynamic modulus values measured in the laboratory. Five newly built Superpave pavements, designed by using the 1993 AASHTO Design Guide, were selected as study sites in this research. Deflection data were collected with a Dynatest 8000 FWD on a 1,000-ft test section at each site. The HMA layer moduli were then backcalculated by using an elastic-layer analysis program. Full depth cores were taken from each section and tested in the laboratory for dynamic moduli. The results showed that backcalculated and laboratory moduli were somewhat comparable for all practical purposes. The laboratory dynamic moduli increased with the loading frequency, indicating the need for consideration of vehicle speeds in the HMA pavement structural design. HMA design moduli, assumed by the Kansas Department of Transportation during pavement structural design, are lower than both backcalculated and laboratory dynamic moduli. Thus, current HMA design moduli are achievable in the field through Superpave mixture design, despite the fact that the pavement structural design and mix design processes are not integrated.
Updating the Pavement Design Catalog for the Washington State Department of Transportation
Authors: Li Jianhua , Uhlmeyer Jeff S. , Mahoney Joe P. , Muench Stephen T.
Published: November 2010

This paper describes the preparation of a revised pavement thickness design catalog for the Washington State Department of Transportation (WSDOT) that used the 1993 AASHTO Guide, the Mechanistic–Empirical Pavement Design Guide (MEPDG), and WSDOT historical pavement performance data. Selection of the design equivalent single-axle load levels and performance criteria are presented, followed by discussion about how the 1993 AASHTO Guide and MEPDG, version 1.0, results were used to guide thickness choices for the catalog. Importantly, the process also included historical pavement performance, the properties of new pavement materials, regional practices, and construction variability as equally valuable inputs. Emphasis was placed on observations and issues encountered by using the current 1993 AASHTO Guide and the MEPDG. The proposed design catalog has been implemented by WSDOT.
Investigation of Hot-Mix Asphalt Dynamic Modulus by Means of Field-Measured Pavement Response
Authors: Bayat Alireza , Knight Mark
Published: November 2010

The current Mechanistic–Empirical Pavement Design Guide (MEPDG) proposes the use of the laboratory dynamic modulus test to determine time–temperature-dependent properties of hot-mix asphalt (HMA) materials. To date, limited measurements have been performed to compare the HMA behavior of laboratory dynamic modulus test with the field measured pavement response. The objectives of this study were to compare and validate laboratory-determined HMA dynamic modulus with field-measured asphalt longitudinal strains. Under constant loading frequency, the laboratory-determined dynamic modulus for Hot Laid 3 (HL3) was found to decrease exponentially when the temperature of the asphalt mix increased. Controlled wheel load experiments, performed at a constant truck speed, found that HL3 asphalt longitudinal strain increased exponentially with an increase in asphalt middepth temperature. The comparison of both exponential relationships showed that the laboratory-determined dynamic modulus was inversely proportional to the field-measured asphalt longitudinal strain.
Influence of Base Clearance on Subgrade Resilient Modulus of Florida Roadway Pavements
Authors: Ping W. Virgil , Sheng Biqing , Ling Ching-Chin , Dietrich Bruce , Horhota David
Published: November 2010

The resilient modulus of pavement subgrade materials is an essential parameter for mechanistically based flexible pavement design procedures. “Base clearance” is defined as the clearance between the ground-water level and the pavement base layer within a pavement system. A high pavement moisture content, which is strongly influenced by the base clearance, causes detrimental effects on the resilient modulus of pavement subgrades. The determination of a pavement base clearance is one of the most important steps toward setting up grade lines in a roadway design. This paper presents an experimental study to evaluate the effects of base clearance on the resilient modulus of pavement subgrades. Full-scale dynamic pavement tests were conducted in test pits to simulate vehicle dynamic impact on field pavements. The level of base clearance was adjusted by raising or lowering the water level within the pavement layer in the pit. Ten types of Florida subgrade material were tested at different base clearances for this study. The dynamic plate load test results were compared with the resilient modulus obtained from the laboratory triaxial test by using layer theory. The differences between the resilient modulus from the laboratory test and the plate load test were typically about 20%. Resilient modulus measured from the laboratory triaxial test could be used to predict the resilient deformation of the pavement subgrade layers. The experimental results showed that, at lower base clearances, the high pavement moisture content caused a significant reduction of the resilient modulus of pavement subgrade layers. The resilient modulus of subgrade materials decreases with the decrease of base clearance.
Process to Estimate Permit Costs for Movement of Heavy Trucks on Flexible Pavements
Authors: Tirado Cesar , Carrasco Cesar , Mares Jose M. , Gharaibeh Nasir , Nazarian Soheil , Bendaña Julian
Published: November 2010

A process based on a mechanistic–empirical (ME) analysis was developed to estimate permit fees on the basis of truck-axle loading and configuration as well as the predicted pavement deterioration that they cause. The process was implemented in a software package, Integrated Pavement Damage Analyzer (IntPave). IntPave is a finite element–based program that calculates pavement responses, uses ME distress models to predict performance under any type of traffic load, is capable of comparing the level of distress caused by a heavy truck relative to a standard truck, and accordingly provides a permit fee. On the basis of a parametric study, it was found that, aside from the truck gross vehicle weight and axle configuration, pavement structure and the damage threshold to rehabilitation also heavily affect the permit fee.
Impulse Purchasing Behaviors of the Turkish Consumers in Websites as a Dynamic Consumer Model: Technology Products Example
Authors: Atici Bünyamin , Bati Ugur
Published: November 2010

This paper examines the concept of impulse purchasing behavior online basically. The phenomenon of impulse purchasing has been researched in consumer research as well as for example in psychology and economics since the 1950s. A detailed review and analysis of the literature asserts that there are some unsolved issues regarding the state of knowledge on impulse purchasing behavior. Furthermore, nowadays consumers buy an increasing amount of purchases on the Internet. The current conceptualizations of impulse purchase behavior do not adequately capture impulse purchase behavior over the Internet. Today several researchers have claimed that the phenomenon of impulse purchasing should be examined also in the context of online shopping environment. This article aims to reveal that what attitudes of the customers are the points in question while purchasing on internet in terms of impulse buying. The results of our exploratory research are consistent with our conceptualization, and present a strong base for future research.
Universal Features for the Classification of Coding and Non-coding DNA Sequences
Authors: Carels Nicolas , Vidal Ramon , Frías Diego
Published: November 2010

In this report, we revisited simple features that allow the classification of coding sequences (CDS) from non-coding DNA. The spectrum of codon usage of our sequence sample is large and suggests that these features are universal. The features that we investigated combine (i) the stop codon distribution, (ii) the product of purine probabilities in the three positions of nucleotide triplets, (iii) the product of Cytosine, Guanine, Adenine probabilities in 1st, 2nd, 3rd position of triplets, respectively, (iv) the product of G and C probabilities in 1st and 2nd position of triplets. These features are a natural consequence of the physico-chemical properties of proteins and their combination is successful in classifying CDS and non-coding DNA (introns) with a success rate >95% above 350 bp. The coding strand and coding frame are implicitly deduced when the sequences are classified as coding.
An Improved Approach for Mapping Quantitative Trait Loci in a Pseudo-Testcross: Revisiting a Poplar Mapping Study
Authors: Wu Song , Yang Jie , Huang Youjun , Li Yao , Yin Tongming , Wullschleger Stan D. , Tuskan Gerald A. , Wu Rongling
Published: November 2010

A pseudo-testcross pedigree is widely used for mapping quantitative trait loci (QTL) in outcrossing species, but the model for analyzing pseudo-testcross data borrowed from the inbred backcross design can only detect those QTLs that are heterozygous only in one parent. In this study, an intercross model that incorporates the high heterozygosity and phase uncertainty of outcrossing species was used to reanalyze a published data set on QTL mapping in poplar trees. Several intercross QTLs that are heterozygous in both parents were detected, which are responsible not only for biomass traits, but also for their genetic correlations. This study provides a more complete identification of QTLs responsible for economically important biomass traits in poplars.
Effect of Diet Supplementation on the Expression of Bovine Genes Associated with Fatty Acid Synthesis and Metabolism
Authors: Joseph Sandeep J. , Robbins Kelly R. , Pavan Enrique , Pratt Scott L. , Duckett Susan K. , Rekaya Romdhane
Published: November 2010

Conjugated linoleic acids (CLA) are of important nutritional and health benefit to human. Food products of animal origin are their major dietary source and their concentration increases with high concentrate diets fed to animals. To examine the effects of diet supplementation on the expression of genes related to lipid metabolism, 28 Angus steers were fed either pasture only, pasture with soybean hulls and corn oil, pasture with corn grain, or high concentrate diet. At slaughter, samples of subcutaneous adipose tissue were collected, from which RNA was extracted. Relative abundance of gene expression was measured using Affymetrix GeneChip Bovine Genome array. An ANOVA model nested within gene was used to analyze the background adjusted, normalized average difference of probe-level intensities. To control experiment wise error, a false discovery rate of 0.01 was imposed on all contrasts. Expression of several genes involved in the synthesis of enzymes related to fatty acid metabolism and lipogenesis such as stearoyl-CoA desaturase (SCD), fatty acid synthetase (FASN), lipoprotein lipase (LPL), fatty-acyl elongase (LCE) along with several trancription factors and co-activators involved in lipogenesis were found to be differentially expressed. Confirmatory RT-qPCR was done to validate the microarray results, which showed satisfactory correspondence between the two platforms. Results show that changes in diet by increasing dietary energy intake by supplementing high concentrate diet have effects on the transcription of genes encoding enzymes involved in fat metabolism which in turn has effects on fatty acid content in the carcass tissue as well as carcass quality. Corn supplementation either as oil or grain appeared to significantly alter the expression of genes directly associated with fatty acid synthesis.
A Plausible Role for the Presence of Internal Shine-Dalgarno Sites
Authors: Ponnala Lalit
Published: November 2010

The presence of nucleotide hybridization between the 3′ end of 16S rRNA and mRNA sequence upstream of the start codon is well known in bacteria. In this paper, we detect the presence of such hybridization sites inside the coding regions of E. coli genes, and analyze their proximity to clusters of slow-translating codons. We study this phenomenon in genes of high and low expression separately. Based on our findings, we propose an explanation for the presence of RNA hybridization within the translated regions of bacterial genes.
Candidate Single Nucleotide Polymorphism Markers for Arsenic Responsiveness of Protein Targets
Authors: Isokpehi Raphael D. , Cohly Hari H.P. , Anyanwu Matthew N. , Rajnarayanan Rajendram V. , Tchounwou Paul B. , Udensi Udensi K. , Graham-Evans Barbara E.
Published: November 2010

Arsenic is a toxic metalloid that causes skin cancer and binds to cysteine residues—a property that could be used to infer arsenic responsiveness of a target protein. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) result in amino acid substitutions and may alter arsenic binding with cysteine residues. Thus, the objective of this investigation was to identify and analyze nsSNPs that lead to substitutions to or from cysteine residues as an indication of increased or decreased arsenic responsiveness. We hypothesize that integration of data on molecular impacts of nsSNPs and arsenic-gene relationships will identify nsSNPs that could serve as arsenic responsiveness markers. We have analyzed functional and structural impacts data for 5,811 nsSNPs linked to 1,224 arsenic-annotated genes. In addition to the identified candidate nsSNPs for increased or reduced arsenic responsiveness, we observed i) a nsSNP that results in the breakage of a disulfide bond, as candidate marker for reduced arsenic responsiveness of KLK7, a secreted serine protease participate in normal shedding of the skin; and ii) 6 pairs of vicinal cysteines in KLK7 protein that could be binding sites for arsenic. In summary, our analysis identified non-synonymous SNPs that could be used to evaluate responsiveness of a protein target to arsenic. In particular, an epidermal expressed serine protease with crucial function in normal skin physiology was prioritized on the basis of abundance of vicinal cysteines for further research on arsenic-induced keratinocyte carcinogenesis.
An Allergen Portrait Gallery: Representative Structures and an Overview of IgE Binding Surfaces
Authors: Schein Catherine H. , Ivanciuc Ovidiu , Midoro-Horiuti Terumi , Goldblum Randall M. , Braun Werner
Published: November 2010

Recent progress in the biochemical classification and structural determination of allergens and allergen–antibody complexes has enhanced our understanding of the molecular determinants of allergenicity. Databases of allergens and their epitopes have facilitated the clustering of allergens according to their sequences and, more recently, their structures. Groups of similar sequences are identified for allergenic proteins from diverse sources, and all allergens are classified into a limited number of protein structural families. A gallery of experimental structures selected from the protein classes with the largest number of allergens demonstrate the structural diversity of the allergen universe. Further comparison of these structures and identification of areas that are different from innocuous proteins within the same protein family can be used to identify features specific to known allergens. Experimental and computational results related to the determination of IgE binding surfaces and methods to define allergen-specific motifs are highlighted.
Generation of Active Bovine Terminal Deoxynucleotidyl Transferase (TdT) in E.coli
Authors: Kuan Wee Liang , Joy Joma , Mee Ng Fui , Perlyn Kwek Zekui , Wen Then Siew , Nguen Thuy , James Joanne , Chai Elaine , Flotow Horst , Crasta Sharon , Chua Kelvin , Peng Ng Sok , Hill Jeffrey
Published: November 2010

A synthetic gene encoding bovine terminal deoxynucleotidyl transferase (TdT) was generated, cloned into an expression vector and expressed in E.coli. The effects of altering culture and induction conditions on the nature of recombinant protein production were investigated. This led to the expression of active recombinant bovine TdT in E.coli. After purification and characterisation, the activity of the enzyme was assessed in a biological assay for apoptosis. The process described in this report enables the economical production of TdT for high throughput applications.
An Event-Related Study for Dynamic Analysis of Corticomuscular Connectivity
Authors: Bai Ou , Huang Dandan , Lin Peter , Wu Jinglong , Chen Xuedong , Fei Ding-Yu
Published: November 2010

Corticomuscular coupling estimated by EEG-EMG coherence may reveal functional cortical driving of peripheral muscular activity. EEG-EMG coherence in the beta band (15–30 Hz) has been extensively studied under isometric muscle contraction tasks. We attempted to study the time-course of corticomuscular connectivity under a dynamic target tracking task. A new device was developed for the real-time measurement of dynamic force created by pinching thumb and index fingers. Four healthy subjects who participated in this study were asked to track visual targets with the feedback forces. Spectral parameters using FFT and complex wavelet were explored for reliable estimation of event-related coherence and EEG-EMG correlogram for representing corticomuscular connectivity. Clearly distinguishable FFT-based coherence and cross-correlogram during the visual target tracking were observed with appropriate hyper-parameters for spectral estimation. The system design and the exploration of signal processing methods in this study supports further exploration of corticomuscular connectivity associated with human motor control.
Computational Methodologies for Analyzing, Modeling and Controlling Gene Regulatory Networks
Authors: Zamani Zahra , Hajihosseini Amirhossein , Masoudi-Nejad Ali
Published: November 2010

Molecular biology focuses on genes and their interactions at the transcription, regulation and protein level. Finding genes that cause certain behaviors can make therapeutic interventions more effective. Although biological tools can extract the genes and perform some analyses, without the help of computational methods, deep insight of the genetic function and its effects will not occur. On the other hand, complex systems can be modeled by networks, introducing the main data as nodes and the links in-between as the transactions occurring within the network. Gene regulatory networks are examples that are modeled and analyzed in order to gain insight of their exact functions. Since a cell's specific functionality is greatly determined by the genes it expresses, translation or the act of converting mRNA to proteins is highly regulated by the control network that directs cellular activities. This paper briefly reviews the most important computational methods for analyzing, modeling and controlling the gene regulatory networks.
Identification of Gene Expression Signature in Estrogen Receptor Positive Breast Carcinoma
Authors: Thakkar Arvind D. , Raj Hemanth , Chakrabarti Debarshi , Ravishankar  , Saravanan N. , Muthuvelan Bhaskaran , Balakrishnan Arun , Padigaru Muralidhara
Published: November 2010

A significant group of patient with estrogen receptor (ER) α positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERα status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERα (+) and ERα (–) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes ( NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT-qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant overexpression of all the six genes in ERα (+) breast tumors as compared to ERα (–) breast tumors. In vitro studies using T-47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes ( SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies “candidate biomarkers” that could be useful for predicting endocrine responsiveness.
Association ofCYP1B1Polymorphisms with Breast Cancer: A Case-Control Study in the Han Population in Ningxia Hui Autonomous Region, P. R. China
Authors: Jiao Haiyan , Liu Chunlian , Guo Weidong , Peng Liang , Chen Yintao , Martin Francis L.
Published: November 2010

Studies investigating possible associations between cytochrome P4501B1 ( CYP1B1) polymorphisms and breast cancer risk have been inconsistent. We set out to ascertain whether there might be an association between polymorphisms in exon 2 (codon 119, G→T) and exon 3 (codon 432, G→C) of CYP1B1 and breast cancer in a Chinese Han population in the rural region of Ningxia. Using an allele-specific polymerase chain reaction method and direct DNA sequencing, the presence or absence of the two CYP1B1 polymorphisms was investigated. Genotype and allele frequencies were analyzed in breast cancer cases (n = 152) and healthy age-matched controls (n = 156). The odds ratio (OR) of 119G→T or 432G→C in breast cancer cases and controls was 3.3 (95% CI: 1.28 to 8.28) and 2.8 (95% CI: 1.04 to 7.51), respectively. In addition, the OR for people with both polymorphisms (119T and 432C) was 4.69 (95% CI: 1.97 to 11.19). Our results suggest that certain polymorphisms in the CYP1B1 gene might increase risk for breast cancer among Han Chinese, perhaps because they influence the efficiency of CYP1B1 bio-transformation of oestrogens or pro-carcinogens into DNA-reactive electrophiles that may act as cancer-initiating agents.
Elevated Serum Sorbitol and not Fructose in Type 2 Diabetic Patients
Authors: Preston Gregory M. , Calle Roberto A.
Published: November 2010

Reductions in fasting serum fructose or erythrocyte sorbitol have been proposed as markers for early proof of mechanism in clinical development of aldose reductase (AR) inhibitors. However fructose is significantly impacted by meals and evaluation of erythrocyte sorbitol poses technical challenges. To more accurately assess the performance of these markers in biological samples, a gas chromatography-mass spectrometry assay was modified and validated. Serum was collected on three consecutive days from 13 healthy volunteers (HV) and 14 patients with type 2 diabetes mellitus (T2DM), and assayed for sorbitol and fructose using this assay. Serum fructose and sorbitol were relatively constant across the three days. Fasting fructose levels were comparable between the two groups (T2DM: 1.48 ± 0.49 mg/L; HV: 1.39 ± 0.38 mg/L, mean ± standard deviation, P = 0.61), but fasting sorbitol levels were significantly higher in diabetics (T2DM: 0.280 ± 0.163 mg/L; HV: 0.164 ± 0.044 mg/L, P = 0.02). Feeding resulted in a 5–6 fold increase in serum fructose levels, but only a 5%-10% increase in sorbitol. Only sorbitol remained significantly elevated pre- and post feeding in T2DM patients relative to HV. These data suggest that serum sorbitol may be a robust proof of mechanism biomarker and facilitate dose selection for clinical development of AR inhibitors.
The Common FTO Genetic Polymorphism rs9939609 is Associated with Increased BMI in Type 1 Diabetes but not with Diabetic Nephropathy
Authors: Gu Harvest F. , Alvarsson Alexandra , Brismar Kerstin
Published: November 2010

The fat mass and obesity associated (FTO) gene has an important genetic effect on body mass index (BMI) and risk of obesity, and obesity contributes to the progression of renal diseases, including diabetic nephropathy. We thus conducted a genetic association study to evaluate whether the FTO gene confers the risk susceptibility to the development of diabetic nephropathy. Genotyping experiments of the common FTO polymorphism, rs9939609, in 1170 type 1 diabetes patients with (n = 597) or without diabetic nephropathy (n = 573) were performed with TaqMan allelic discrimination. All subjects are of European descent and selected from the Genetics of Kidney Diseases in Diabetes (GoKinD) study. The frequency of T allele of this polymorphism was 0.414 in the studied population. There was no allelic association of this polymorphism with diabetic nephropathy. But, the risk susceptibility of A allele conferring to the increased BMI among type 1 diabetes patients was observed. The subjects carrying with AA genotype had higher BMI compared to the carriers with TA and/or TT genotype(s) ( P ≥ 0.019). The present study provides evidence that the common FTO genetic polymorphism, rs9939609, is associated with increased BMI in type 1 diabetes but not with diabetic nephropathy.
Feasibility of High-Throughput Genome-Wide Genotyping using DNA from Stored Buccal Cell Samples
Authors: Loomis Stephanie J. , Olson Lana M. , Pasquale Louis R. , Wiggs Janey , Mirel Daniel , Crenshaw Andrew , Parkin Melissa , Rahhal Brandon , Tetreault Stephanie , Kraft Peter , Tworoger Shelley S. , Haines Jonathan L. , Kang Jae H.
Published: November 2010

It is unclear if buccal cell samples contain sufficient human DNA with adequately sized fragments for high throughput genetic bioassays. Yet buccal cell sample collection is an attractive alternative to gathering blood samples for genetic epidemiologists engaged in large-scale genetic biomarker studies. We assessed the genotyping efficiency (GE) and genotyping concordance (GC) of buccal cell DNA samples compared to corresponding blood DNA samples, from 32 Nurses' Health Study (NHS) participants using the Illumina Infinium 660W-Quad platform. We also assessed how GE and GC accuracy varied as a function of DNA concentration using serial dilutions of buccal DNA samples. Finally we determined the nature and genomic distribution of discordant genotypes in buccal DNA samples. The mean GE of undiluted buccal cell DNA samples was high (99.32%), as was the GC between the paired buccal and blood samples (99.29%). GC between the dilutions versus the undiluted buccal DNA was also very high (>97%), though both GE and GC notably declined at DNA concentrations less than 5 ng/μl. Most (>95%) genotype determinations in buccal cell samples were of the “missing call” variety (as opposed to the “alternative genotype call” variety) across the spectrum of buccal DNA concentrations studied. Finally, for buccal DNA concentration above 1.7 ng/ul, discordant genotyping calls did not cluster in any particular chromosome. Buccal cell-derived DNA represents a viable alternative to blood DNA for genotyping on a high-density platform.
LSOSS: Detection of Cancer Outlier Differential Gene Expression
Authors: Wang Yupeng , Rekaya Romdhane
Published: November 2010

Detection of differential gene expression using microarray technology has received considerable interest in cancer research studies. Recently, many researchers discovered that oncogenes may be activated in some but not all samples in a given disease group. The existing statistical tools for detecting differentially expressed genes in a subset of the disease group mainly include cancer outlier profile analysis (COPA), outlier sum (OS), outlier robust t-statistic (ORT) and maximum ordered subset t-statistics (MOST). In this study, another approach named Least Sum of Ordered Subset Square t-statistic (LSOSS) is proposed. The results of our simulation studies indicated that LSOSS often has more power than previous statistical methods. When applied to real human breast and prostate cancer data sets, LSOSS was competitive in terms of the biological relevance of top ranked genes. Furthermore, a modified hierarchical clustering method was developed to classify the heterogeneous gene activation patterns of human breast cancer samples based on the significant genes detected by LSOSS. Three classes of gene activation patterns, which correspond to estrogen receptor (ER)+, ER– and a mixture of ER+ and ER–, were detected and each class was assigned a different gene signature.
Assessment of mRNA and microRNA Stabilization in Peripheral Human Blood for Multicenter Studies and Biobanks
Authors: Weber Daniel Gilbert , Casjens Swaantje , Rozynek Peter , Lehnert Martin , Zilch-Schöneweis Sandra , Bryk Oleksandr , Taeger Dirk , Gomolka Maria , Kreuzer Michaela , Otten Heinz , Pesch Beate , Johnen Georg , Brüning Thomas
Published: November 2010

In this study we evaluate the suitability of two methods of RNA conservation in blood samples, PAXgene and RNAlater, in combination with variable shipping conditions for their application in multicenter studies and biobanking. RNA yield, integrity, and purity as well as levels of selected mRNA and microRNA species were analyzed in peripheral human blood samples stabilized by PAXgene or RNAlater and shipped on dry ice or at ambient temperatures from the study centers to the central analysis laboratory. Both examined systems were clearly appropriate for RNA stabilization in human blood independently of the shipping conditions. The isolated RNA is characterized by good quantity and quality and well suited for downstream applications like quantitative RT-PCR analysis of mRNA and microRNA. Superior yield and integrity values were received using RNAlater. It would be reasonable to consider the production and approval of blood collection tubes prefilled with RNAlater to facilitate the use of this excellent RNA stabilization system in large studies.
Standardization of Gene Expression Quantification by Absolute Real-Time qRT-PCR System Using a Single Standard for Marker and Reference Genes
Authors: Zhou Yi-Hong , Raj Vinay R. , Siegel Eric , Yu Liping
Published: November 2010

In the last decade, genome-wide gene expression data has been collected from a large number of cancer specimens. In many studies utilizing either microarray-based or knowledge-based gene expression profiling, both the validation of candidate genes and the identification and inclusion of biomarkers in prognosis-modeling has employed real-time quantitative PCR on reverse transcribed mRNA (qRT-PCR) because of its inherent sensitivity and quantitative nature. In qRT-PCR data analysis, an internal reference gene is used to normalize the variation in input sample quantity. The relative quantification method used in current real-time qRT-PCR analysis fails to ensure data comparability pivotal in identification of prognostic biomarkers. By employing an absolute qRT-PCR system that uses a single standard for marker and reference genes (SSMR) to achieve absolute quantification, we showed that the normalized gene expression data is comparable and independent of variations in the quantities of sample as well as the standard used for generating standard curves. We compared two sets of normalized gene expression data with same histological diagnosis of brain tumor from two labs using relative and absolute real-time qRT-PCR. Base-10 logarithms of the gene expression ratio relative to ACTB were evaluated for statistical equivalence between tumors processed by two different labs. The results showed an approximate comparability for normalized gene expression quantified using a SSMR-based qRT-PCR. Incomparable results were seen for the gene expression data using relative real-time qRT-PCR, due to inequality in molar concentration of two standards for marker and reference genes. Overall results show that SSMR-based real-time qRT-PCR ensures comparability of gene expression data much needed in establishment of prognostic/predictive models for cancer patients–-a process that requires large sample sizes by combining independent sets of data.
Article Commentary: A Commentary on “Evaluation of the in vitro Bioactivity of Bioceramics”
Authors: Hsu Y.H. , Turner I.G. , Miles A.W.
Published: November 2010

The interesting article reported in Bone and Tissue Regeneration Insights by Wu and Xiao entitled “Evaluation of the in vitro bioactivity of bioceramics” contrasts two methods (Simulated body fluid (SBF) and cell culture experiments) which have been commonly used to evaluate the in vitro bioactivity of bioceramics. Limitations in estimating the bioactivity of bioceramics using both methods have been reviewed. Therefore, Wu and Xiao suggest the combination of these two methods to evaluate the bioactivity of bioceramics can improve the screening efficiency for the selection of bioactive ceramics for bone regeneration.
Seasonal variations of aerosol size distributions based on long-term measurements at the high altitude Himalayan site of Nepal Climate Observatory-Pyramid (5079 m), Nepal
Authors: Sellegri K. , Laj P. , Venzac H. , Boulon J. , Picard D. , Villani P. , Bonasoni P. , Marinoni A. , Cristofanelli P. , Vuillermoz E.
Published: November 2010

Abstract. The present paper investigates the diurnal and seasonal variability of the aerosol total number concentration, number and volume size distribution between 10 nm and 10 μm, from a combination of a scanning mobility particle sizer (SMPS) and an optical counter (OPC), performed over a two-year period (January 2006–February 2008) at the Nepal Climate Observatory-Pyramid (NCO-P) research station, (5079 m a.s.l.). The annual average number concentration measured over the two-year period at the NCO-P is 860 cm−3. Total concentrations show a strong seasonality with maxima during pre-monsoon and post-monsoon seasons and minima during the dry and monsoon seasons. A diurnal variation is also clearly observed, with maxima between 09:00 and 12:00 UTC. The aerosol concentration maxima are mainly due to nucleation processes during the post-monsoon season, as witnessed by high nucleation mode integrated number concentrations, and to transport of high levels of pollution from the plains by valley breezes during the pre-monsoon season, as demonstrated by high accumulation mode integrated number concentrations. Night-time number concentration of particles (from 03:00 to 08:00 NST) are relatively low throughout the year (from 450 cm−3 during the monsoon season to 675 cm−3 during the pre-monsoon season), indicating the of high altitudes background level, as a result of downslope winds during this part of the day. However, it was found that these background concentrations are strongly influenced by the daytime concentrations, as they show the same seasonal variability. If nighttime concentrations were presumed to be representative of free troposphere (FT)/residual layer concentrations, they would be found to be two times higher than at other lower altitudes European sites, such as the Jungfraujoch. However, BL intrusions might contaminate the free troposphere/residual layer even at this altitude, especially during regional air masses influence. Night-time measurements were subsequently selected to study the FT composition according to different air masses, and the effect of long range transport to the station.
CO2, δO2/N2 and APO: observations from the Lutjewad, Mace Head and F3 platform flask sampling network
Authors: van der Laan-Luijkx I. T. , Karstens U. , Steinbach J. , Gerbig C. , Sirignano C. , Neubert R. E. M. , van der Laan S. , Meijer H. A. J.
Published: November 2010

Abstract. We report results from our atmospheric flask sampling network for three European sites: Lutjewad in the Netherlands, Mace Head in Ireland and the North Sea F3 platform. The air samples from these stations are analyzed for their CO2 and O2 concentrations. In this paper we present the CO2 and O2 data series from these sites between 1998 and 2009, as well as the atmospheric potential oxygen (APO). The seasonal pattern and long term trends agree to a large extent between our three measurement locations. We however find a changing gradient between Mace Head and Lutjewad, both for CO2 and O2. To explain the potential contribution of fossil fuel emissions to this changing gradient we use an atmospheric transport model in combination with CO2 emission data and information on the fossil fuel mix per region. Using the APO trend from Mace Head we obtain an estimate for the global oceanic CO2 uptake of 1.8 ± 0.8 PgC/year.
Emission factors for open and domestic biomass burning for use in atmospheric models
Authors: Akagi S. K. , Yokelson R. J. , Wiedinmyer C. , Alvarado M. J. , Reid J. S. , Karl T. , Crounse J. D. , Wennberg P. O.
Published: November 2010

Abstract. Biomass burning (BB) is the second largest source of trace gases and the largest source of primary fine carbonaceous particles in the global troposphere. Many recent BB studies have provided new emission factor (EF) measurements. This is especially true for non methane organic compounds (NMOC), which influence secondary organic aerosol (SOA) and ozone formation. New EF should improve regional to global BB emissions estimates and therefore, the input for atmospheric models. In this work we present an up-to-date, comprehensive tabulation of EF for known pyrogenic species based on measurements made in smoke that has cooled to ambient temperature, but not yet undergone significant photochemical processing. All the emission factors are converted to one standard form (g compound emitted per kg dry biomass burned) using the carbon mass balance method and they are categorized into 14 fuel or vegetation types. We compile a large number of measurements of biomass consumption per unit area for important fire types and summarize several recent estimates of global biomass consumption by the major types of biomass burning. Biomass burning terminology is defined to promote consistency. Post emission processes are discussed to provide a context for the emission factor concept within overall atmospheric chemistry and also highlight the potential for rapid changes relative to the scale of some models or remote sensing products. Recent work shows that individual biomass fires emit significantly more gas-phase NMOC than previously thought and that including additional NMOC can improve photochemical model performance. A detailed global estimate suggests that BB emits at least 400 Tg yr−1 of gas-phase NMOC, which is about 4 times larger than most previous estimates. Selected recent results (e.g. measurements of HONO and the BB tracers HCN and CH3CN) are highlighted and key areas requiring future research are briefly discussed.