bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification and Reorganization of the Cytoprotective Cellular Chaperone Hsp27 during Herpes Simplex Virus Type 1 Infection
Authors: Mathew Shomita S. , Della Selva Megan P. , Burch April D.
Published: July 2009

Chaperone-enriched domains are formed in the nuclei of cells lytically infected with herpes simplex virus type 1 (HSV-1). These domains, called VICE, forvirusinducedchaperoneenriched, contain Hsc70, Hsp70, Hsp40, Hsp90, polyubiquitinated proteins, and components of the proteasome machinery. Accumulating evidence indicates that these sites may be utilized during infection to sequester misfolded, modified, or otherwise unwanted proteins away from viral replication compartments, sites of robust transcription, DNA synthesis, and capsid maturation. To further explore the role of cellular chaperones and VICE domains during HSV-1 infection, we have analyzed the cytoprotective chaperone Hsp27. Here we present evidence that Hsp27, which is known to possess several antioxidant functions, is rapidly reorganized and modified at early stages in response to HSV-1 infection and signaling from the mitogen-activated protein kinase p38. Immunofluorescence analysis and fractionation experiments reveal disparate subcellular localizations of nonphosphorylated and phosphorylated forms of Hsp27 during wild-type HSV-1 infection. Unmodified forms of Hsp27 are localized in nuclear foci that are outside of replication compartments, adjacent to VICE domains, and in the cytoplasm. Conversely, we find that phosphorylated forms of Hsp27 are localized exclusively in the cytoplasm. Last, in cells depleted of all forms of Hsp27, virus replication is significantly reduced.
A high-resolution late-glacial and early Holocene diatom record from Baffin Island, eastern Canadian Arctic
Authors: Wolfe Alexander P.
Published: July 2009

An interval of late-glacial to early Holocene sedimentation, spanning the period 12.9–8.4 ka BP (14C dated by accelerator mass spectrometry), is contained within 15 cm of gyttja in a core from a small lake on southwestern Cumberland Peninsula, Baffin Island. This sediment was subsampled in continuous 2.5 mm increments for diatom analysis. Extremely low sediment accumulation rates (~1.8 cm ka−1) are characteristic of the initial phase of organic sedimentation, but they increase rapidly (to 14.2 cm ka−1) after 9 ka BP. The first 0.5 cm of gyttja contained an acidophilous diatom flora resembling that of underlying mineral sediments. Thereafter, and throughout the late glacial and earliest Holocene, diatom floras were dominated by alkaliphilous and circumneutral species of Fragilaria. Around 9 ka BP, shifts to acidophilous floras dominated by Brachysira brebissonii, and, later, Eunotia rhomboidea and Frustulia rhomboides vars. saxonica and crassinervia, suggest a period of natural lake acidification. High diatom production accompanied the lowered lake-water pH, which reflects, respectively, the paleolimnological response to an early Holocene climatic optimum, and progressive depletion of lake alkalinity sources. There is no evidence of diatom or sediment responses attributable to the Younger Dryas oscillation, implying that deglacial reorganizations of the North Atlantic Ocean did not necessarily affect paleoclimatic conditions in the southern Cumberland Sound region.
Estimation of standing dead tree class distributions in northwest coastal forests using lidar remote sensing
Authors: Bater Christopher W. , Coops Nicholas C. , Gergel Sarah E. , LeMay Valerie , Collins Denis
Published: July 2009

The amount and variability of living and dead wood in a forest stand are important indicators of forest biodiversity, as it relates to structural heterogeneity and habitat availability. In this study, we investigate whether light detection and ranging (lidar) can be used to estimate the distribution of standing dead tree classes within forests. Twenty-two field plots were established in which each stem (DBH >10 cm) was assigned to a wildlife tree (WT) class. For each plot, a suite of lidar-derived predictor variables were extracted. Ordinal regression using a negative log–log link function was then employed to predict the cumulative proportions of stems within the WT classes. Results indicated that the coefficient of variation of the lidar height data was the best predictor variable (χ2 = 106.11, p < 0.00; Wald = 4.83, p = 0.028). The derived relationships allowed for the prediction of the cumulative proportion of stems within WT classes (r = 0.90, RMSE = 6.0%) and the proportion of dead stems within forest plots (r = 0.61, RMSE = 16.8%). Our research demonstrates the capacity of lidar remote sensing to estimate the relative abundances of standing living and dead trees in forest stands and its ability to characterize vegetation structure across large spatial extents.
Temporal dynamics of large woody debris in small streams of the Alberta foothills, Canada
Authors: Powell S.R. , Daniels L.D. , Jones T.A.
Published: July 2009

Large woody debris (LWD) is a key link between riparian forests and streams; however, the temporal dynamics of in-stream wood remains poorly quantified. Using dendrochronology, we evaluated the dynamics of five Pinus -dominated and five Picea -dominated riparian forests in the foothills of Alberta and cross-dated the ring widths of 186 pieces of LWD. Time since death of LWD ranged from 2 to 143 years, with maximums of 86 and 143 years for Pinus and Picea, respectively. Recruitment of Pinus LWD was influenced by stand-replacing fires followed by self-thinning about 40 years after stand establishment. In uneven-aged Picea-dominated forests, tree mortality and LWD recruitment were due to fine-scale disturbances. Time since death increased significantly with decay and position classes, which resulted in changes in LWD function through time. LWD persisted in the bridge position for about 30 years. Bridged LWD was least decayed, was significantly longer, and had greater volume than LWD in other positions. LWD remained in partial bridge and loose positions about 15 years and >80 years when submerged in water and buried in sediment. Given the persistence of LWD, we conclude that management that alters wood abundance and recruitment has short- and long-term implications for the structure and function of small streams.
Gaining local accuracy while not losing generality — extending the range of gap model applications
Authors: Didion Markus , Kupferschmid Andrea D. , Zingg Andreas , Fahse Lorenz , Bugmann Harald
Published: July 2009

For the study of long-term processes in forests, gap models generally sacrifice accuracy (i.e., simulating system behavior in a quantitatively accurate manner) for generality (i.e., representing a broad range of systems’ behaviors with the same model). We selected the gap model ForClim to evaluate whether the local accuracy of forest succession models can be increased based on a parsimonious modeling approach that avoids the additional complexity of a 3D crown model, thus keeping parameter requirements low. We improved the representation of tree crowns by introducing feedbacks between (i) light availability and leaf area per tree and (ii) leaf area per tree and diameter growth rate to account for the self-pruning in real stands. The local accuracy of the new model, ForClim v2.9.5, was considerably improved in simulations at three long-term forest research sites in the Swiss Alps, while its generality was maintained as shown in simulations of potential natural vegetation along a broad environmental gradient in Central Europe. We conclude that the predictive ability of a model does not depend on its complexity, but on the reproduction of patterns. Most importantly, model complexity should be consistent with the objectives of the study and the level of system understanding.
Mapping and imputing potential productivity of Pacific Northwest forests using climate variables
Authors: Latta Gregory , Temesgen Hailemariam , Barrett Tara M.
Published: July 2009

Regional estimation of potential forest productivity is important to diverse applications, including biofuels supply, carbon sequestration, and projections of forest growth. Using PRISM (Parameter-elevation Regressions on Independent Slopes Model) climate and productivity data measured on a grid of 3356 Forest Inventory and Analysis plots in Oregon and Washington, we evaluated four possible imputation methods to estimate potential forest productivity: nearest neighbour, multiple linear regression, thin plate spline functions, and a spatial autoregressive model. Productivity, measured by potential mean annual increment at culmination, is explained by the interaction of annual temperature, precipitation, and climate moisture index. The data were randomly divided into 2237 reference plots and 1119 target plots 30 times. Each imputation method was evaluated by calculating the coefficient of determination, bias, and root mean square error of both the target and reference data set and was also tested for evidence of spatial autocorrelation. Potential forest productivity maps of culmination potential mean annual increment were produced for all Oregon and Washington timberland.
SEARCHING FOR TARGETS ON A MODEL DNA: EFFECTS OF INTER-SEGMENT HOPPING, DETACHMENT, AND RE-ATTACHMENT
Authors: CHOWDHURY DEBANJAN
Published: July 2009

For most of the important processes in DNA metabolism, a protein has to reach a specific binding site on the DNA. The specific binding site may consist of just a few base-pairs while the DNA is usually several millions of base-pairs long. How does the protein search for the target site? What is the most efficient mechanism for a successful search? Motivated by these fundamental questions on intracellular biological processes, we have developed a model for searching a specific site on a model DNA by a single protein. We have made a comparative quantitative study on the efficiencies of sliding, inter-segmental hoppings and detachment/re-attachments of the particle during its search for the specific site on the DNA. We also introduce some new quantitative measures of efficiency of a search process by defining a relevant quantity, which can be measured in in-vitro experiments.
THE EFFECTS OF BUS STOP ON TRAFFIC FLOW
Authors: TANG TIE-QIAO , LI YAN , HUANG HAI-JUN
Published: July 2009

In this paper, we use the traffic flow model proposed by Tang et al. [Physica A387, 6845 (2008)] to study the effects of bus stop on traffic flow. Our numerical tests show that bus stop will have great effects on the stability of traffic flow and that the effects are related to the initial density and the number of bus stops. The numerical results are accordant with the real traffic, which shows that the model proposed by Tang et al. can describe some complex traffic phenomena resulted by bus stop.
REVIEW OF PROPERTIES OF THE TOP QUARK FROM MEASUREMENTS AT THE TEVATRON
Authors: PLEIER MARC-ANDRÉ
Published: July 2009

This review summarizes the program in the physics of the top quark being pursued at Fermilab's Tevatron proton–antiproton collider at a center-of-mass energy of 1.96 TeV. More than a decade after the discovery of the top quark at the two collider detectors CDF and D0, the Tevatron has been the only accelerator to produce top quarks and to study them directly.

The Tevatron's increased luminosity and center-of-mass energy offer the possibility to scrutinize the properties of this heaviest fundamental particle through new measurements that were not feasible before, such as the first evidence for electroweak production of top quarks and the resulting direct constraints on the involved couplings. Better measurements of top quark properties provide more stringent tests of predictions from the SM of elementary particle physics. In particular, the improvement in measurements of the mass of the top quark, with the latest uncertainty of 0.7% marking the most precisely measured quark mass to date, further constrains the prediction of the mass of the still to be discovered Higgs boson.
Chapter 2 The BES-III Detector and Offline Software
Authors: Li Wei-Dong , Mao Ya-Jun , Wang Yi-Fang
Published: July 2009

The following sections are included:

Overview of the BES-III Detector

BES-III Offline Software

Main Drift Chamber

Time-Of-Flight System

Electromagnetic Calorimeter

Muon Identifier

Trigger
Chapter 4 Physics Processes and Radiative Corrections
Authors: Ma J. P. , Wang Ping
Published: July 2009

The following sections are included:

Physics Processes at BEPC-II

Radiative Corrections
Chapter 6 R Values and Precise Test of the Standard Model
Authors: Hu Hai-Ming , Li Xiao-Yuan
Published: July 2009

The following sections are included:

e+e- → hadrons Cross Sections and the Rhad Value

Hadronic Vacuum Polarization

Input Parameters and their Uncertainties

Measurement of R Value at BES-III
Chapter 29 Tau Decays
Authors: Pich Antonio , Boyko I. , Dedovich D. , Bigi I. I.
Published: July 2009

The following sections are included:

Hadronic τ Decays

Leptonic Tau Decays

Semileptonic Decays

Search for CP Violation in τ Decays
Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans
Authors: Mayhew David L. , Kim Jeong-su , Cross James M. , Ferrando Arny A. , Bamman Marcas M.
Published: July 2009

While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23–199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age × time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend ( P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT.
Genetic Dissection of Rod and Cone Pathways in the Dark-Adapted Mouse Retina
Authors: Abd-El-Barr Muhammad M. , Pennesi Mark E. , Saszik Shannon M. , Barrow Andrew J. , Lem Janis , Bramblett Debra E. , Paul David L. , Frishman Laura J. , Wu Samuel M.
Published: July 2009

A monumental task of the mammalian retina is to encode an enormous range (>109-fold) of light intensities experienced by the animal in natural environments. Retinal neurons carry out this task by dividing labor into many parallel rod and cone synaptic pathways. Here we study the operational plan of various rod- and cone-mediated pathways by analyzing electroretinograms (ERGs), primarily b-wave responses, in dark-adapted wildtype, connexin36 knockout, depolarizing rod–bipolar cell (DBCR) knockout, and rod transducin alpha-subunit knockout mice [ WT, Cx36(−/−), Bhlhb4(−/−), and Trα(−/−)]. To provide additional insight into the cellular origins of various components of the ERG, we compared dark-adapted ERG responses with response dynamic ranges of individual retinal cells recorded with patch electrodes from dark-adapted mouse retinas published from other studies. Our results suggest that the connexin36-mediated rod–cone coupling is weak when light stimulation is weak and becomes stronger as light stimulation increases in strength and that rod signals may be transmitted to some DBCCs via direct chemical synapses. Moreover, our analysis indicates that DBCR responses contribute about 80% of the overall DBC response to scotopic light and that rod and cone signals contribute almost equally to the overall DBC responses when stimuli are strong enough to saturate the rod bipolar cell response. Furthermore, our study demonstrates that analysis of ERG b-wave of dark-adapted, pathway-specific mutants can be used as an in vivo tool for dissecting rod and cone synaptic pathways and for studying the functions of pathway-specific gene products in the retina.
Elastography Method for Reconstruction of Nonlinear Breast Tissue Properties
Authors: Wang Z. G. , Liu Y. , Wang G. , Sun L. Z.
Published: July 2009

Elastography is developed as a quantitative approach to imaging linear elastic properties of tissues to detect suspicious tumors. In this paper a nonlinear elastography method is introduced for reconstruction of complex breast tissue properties. The elastic parameters are estimated by optimally minimizing the difference between the computed forces and experimental measures. A nonlinear adjoint method is derived to calculate the gradient of the objective function, which significantly enhances the numerical efficiency and stability. Simulations are conducted on a three‐dimensional heterogeneous breast phantom extracting from real imaging including fatty tissue, glandular tissue, and tumors. An
exponential‐form of nonlinear material model is applied. The effect of noise is taken into account.
Results demonstrate that the proposed nonlinear method opens the door toward nonlinear elastography
and provides guidelines for future development and clinical application in breast cancer study.
On Perfectly Homogeneous Bases in Quasi‐Banach Spaces
Authors: Albiac F. , Leránoz C.
Published: July 2009

For 0 < p < ∞ the unit vector basis of ℓp has the property of perfect homogeneity: it is equivalent to all its normalized block basic
sequences, that is, perfectly homogeneous bases are a special case of
symmetric bases. For Banach spaces, a classical result of Zippin (1966)
proved that perfectly homogeneous bases are equivalent to either the
canonical c0‐basis or the canonical ℓp‐basis for some 1 ≤ p < ∞. In this note, we show that (a relaxed form of) perfect homogeneity characterizes
the unit vector bases of ℓp for 0 < p < 1 as well amongst bases in nonlocally convex quasi‐Banach spaces.
Tissue Microarray Validation: A Methodologic Study with Special Reference to Lung Cancer
Authors: Karlsson Christina , Bodin Lennart , Piehl-Aulin Karin , Karlsson Mats G.
Published: July 2009

Background: Although tissue microarray (TMA) studies of histopathologic material have been frequently reported in studies of malignant diseases, the question of sample size (i.e., the diameter and the number of tissue cylinders investigated) has been rarely discussed. This study addresses the methodologic question of sample size in a variety of tumor types.

Material and Methods: Material from 29 cases of lung carcinoma (small cell, squamous cell, and adenocarcinomas) was examined immunohistochemically for Ki-67 and p53 expression in virtually constructed cylinders of different diameters. The influence of tissue sample size (i.e., different numbers of virtual cylinders) was also investigated. Results from Ki-67 evaluation were analyzed as a continuous variable, whereas p53 expression was scored. p53 evaluations based on scoring in cylinders versus scoring of whole sections were also compared. Furthermore, 10 cases of endometrial and breast carcinomas were evaluated for estrogen receptor, Ki-67, and HER2 by scoring up to five cylinders.

Results and Conclusions: Tissue cylinders of 0.6 and 1.0 mm diameters were compared and found equally informative about Ki-67 expression (intraclass correlation, 0.96). A statistical approach considering intraindividual and interindividual variation data is presented, indicating that in this specific setting three cylinders per case is an adequate sample size for TMA studies. Further sampling yields only a small gain in accuracy as determined by Ki-67 quantification and p53 scoring (κ-coefficient, 0.9). For endometrial and breast tissues, TMA scoring of three cylinders yielded excellent agreement (κ, >0.75) compared with whole-section scoring. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2014–21)
Dietary Intake of Vegetables and Fruits and the Modification Effects of GSTM1 and NAT2 Genotypes on Bladder Cancer Risk
Authors: Lin Jie , Kamat Ashish , Gu Jian , Chen Meng , Dinney Colin P. , Forman Michele R. , Wu Xifeng
Published: July 2009

We analyzed the association between intakes of vegetables and fruits as defined by the U.S. Department of Agriculture pyramid food groups and bladder cancer risk using data collected in a large case-control study. The study included 884 histologically confirmed bladder cancer cases and 878 healthy controls matched to cases by age (±5 years), gender, and ethnicity. Significant inverse associations were observed for intakes of total vegetables, cruciferous vegetables, orange vegetables, dark green vegetables, and bladder cancer risk. Compared with those in the lowest quartile of total vegetable intake, the odds ratios for the 2nd, 3rd, and 4th quartiles of total vegetable intake were 0.84 [95% confidence interval (95% CI), 0.64-1.10], 0.71 (95% CI, 0.54-0.95), and 0.67 (95% CI, 0.50-0.90), respectively (P for trend = 0.004). Compared with those in the lowest quartile, those in the highest quartile of cruciferous vegetable intake had an odds ratio of 0.69 (95% CI, 0.52-0.92; P for trend = 0.001) and those in the highest quartile of orange vegetable intake had an odds ratio of 0.68 (95% CI, 0.52-0.91; P for trend = 0.006). Furthermore, the protective effect of cruciferous vegetables was more evident in subjects carrying GSTM1-null (odds ratio, 0.43; 95% CI, 0.25-0.73 for the 4th quartile of intake) and NAT2-slow genotypes (odds ratio, 0.56; 95% CI, 0.33-0.97 for the 4th quartile of intake). No association was observed for intakes of total fruits or citrus fruits. Our data strongly support that high vegetable consumption, especially cruciferous vegetable intake, may protect against bladder cancer and that genetic variants of GSTM1 and NAT2 may modify the association. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2090–7)
Eligibility for Magnetic Resonance Imaging Screening in the United Kingdom: Effect of Strict Selection Criteria and Anonymous DNA Testing on Breast Cancer Incidence in the MARIBS Study
Authors: Evans D. Gareth R. , Lennard Fiona , Pointon Linda J. , Ramus Susan J. , Gayther Simon A. , Sodha Nayanta , Kwan-Lim Gek E. , Leach Martin O. , Warren Ruth , Thompson Deborah , Easton Douglas F. , Eeles Rosalind ,   on behalf of The UK study of MRI screening for breast cancer in women at high risk (MARIBS)
Published: July 2009

Introduction: A UK multicenter study compared the performance of contrast enhanced-magnetic resonance imaging with X-Ray Mammography in women at high-risk of breast cancer commencing in 1997. Selection criteria were used to identify women with at least 0.9% annual risk of breast cancer.

Methods: Women at high breast cancer risk, with a strong family history and/or high probability of a BRCA1/BRCA2/TP53 mutation, were recruited from 22 centers. Those not known as gene carriers were asked to give a blood sample, which was tested anonymously for mutations. Women ages 35 to 49 years were offered annual screening for 2 to 7 years. Study eligibility at entry was assessed retrospectively by detailed examination of pedigrees and overall eligibility accounting for computer risk assessment and mutation results.

Results: Seventy-eight of 837 (9%) women entered for screening were ineligible using the strict entry criteria. Thirty-nine cancers were detected in 1,869 women-years in study (incidence 21 per 1,000). Including 3,561 further years follow-up, 28 more breast cancers were identified (12 of 1,000). Incidence rates for 759 eligible women were 22 of 1,000 in study and 13 of 1,000 in total follow-up, compared with 9 of 1,000 and 4 of 1,000, respectively, in 78 ineligible women. Breast cancer rates were higher for BRCA2 than BRCA1 after testing anonymized samples in this selected population at 65 of 1,000 in study and 36 of 1,000 in total follow-up for BRCA2 compared with 44 of 1,000 and 27 of 1,000 for BRCA1.

Conclusions: Strict enforcement of study criteria would have minimally improved the power of the study, whereas testing for BRCA1/2 in advance would have substantially increased the detection rates. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2123–31)
Polymorphisms and Haplotypes in the Caspase-3, Caspase-7, and Caspase-8 Genes and Risk for Endometrial Cancer: A Population-Based, Case-Control Study in a Chinese Population
Authors: Xu Hong-Li , Xu Wang-Hong , Cai Qiuyin , Feng Min , Long Jirong , Zheng Wei , Xiang Yong-Bing , Shu Xiao-Ou
Published: July 2009

Caspase-3, caspase-7, and caspase-8 are important caspases in the apoptosis pathway and play an important role in the development and progression of cancer. We examined the association between genetic variants in the caspase-3, caspase-7, and caspase-8 genes and risk for endometrial cancer among Chinese women. Genotypes for 1,028 women with endometrial cancer and 1,003 healthy controls were determined with the Affymetrix MegAllele Targeted Genotyping System and Molecular Inversion Probe method. Of 35 selected single-nucleotide polymorphisms, four in the caspase-7 gene were in high linkage disequilibrium (rs11593766, rs3124740, rs11196445, and rs11196418) and associated with the risk for endometrial cancer. The AA genotype of rs11196418 [odds ratio, 0.36; 95% confidence interval (95% CI), 0.14-0.94] and the G allele of rs11593766 were associated with reduced risk (odds ratio of 0.75 and 95% CI of 0.59-0.96 for carriers of one G allele; odds ratio of 0.70 and 95% CI of 0.24-2.03 for carriers of two G alleles). The AA genotype of rs11196445 (odds ratio, 1.74; 95% CI, 0.99-3.05), the CC genotype of rs3124740 (odds ratio, 1.36; 95% CI, 1.06-1.75), and the GG genotype of rs10787498 in the caspase-7 gene (odds ratio, 1.90; 95% CI, 1.16-3.11) were associated with increased risk compared with homozygotes of the major alleles. The gene-disease association seemed to be more pronounced among premenopausal women, although tests for multiplicative interaction between genes and menopausal status failed to reach statistical significance. The GG genotype of rs2705901 in the caspase-3 gene was significantly associated with increased cancer risk compared with the CC genotype (odds ratio, 2.25; 95% CI, 1.03-4.95). No association was observed between polymorphisms of the caspase-8 gene and risk for endometrial cancer. These findings suggest that genetic variants in caspase-3 and caspase-7 may play a role in endometrial cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2114–22)
The Etiologic Role of HPV in Vulvar Squamous Cell Carcinoma Fine Tuned
Authors: van de Nieuwenhof Hedwig P. , van Kempen Léon C.L.T. , de Hullu Joanne A. , Bekkers Ruud L.M. , Bulten Johan , Melchers Willem J.G. , Massuger Leon F.A.G.
Published: July 2009

Purpose: High-risk human papilloma virus (HPV) plays a role in the development of a subset of vulvar squamous cell carcinomas. Uncertainty exists about the true impact of HPV in this tumor type because conflicting reports have been published with diverging prevalence rates. This study was done to fine tune the role of high-risk HPV infection in vulvar squamous cell carcinoma development in relation to clinical prognosis.

Experimental Design: 130 vulvar squamous cell carcinomas of patients with known survival data were analyzed for histology of the adjacent lesion (differentiated or HPV-associated usual vulvar intraepithelial neoplasia), in relation to p16INK4A expression as marker of HPV activity, and presence and integration of high-risk HPV DNA.

Results: Usual vulvar intraepithelial neoplasia was present adjacent to vulvar squamous cell carcinoma in 25 of 130 cases. Usual vulvar intraepithelial neoplasia–associated squamous cell carcinomas had high p16INK4A expression, and 24 of 25 squamous cell carcinomas contained integrated high-risk HPV DNA. Differentiated vulvar intraepithelial neoplasia was found adjacent to 105 of 130 vulvar squamous cell carcinomas. High-risk HPV was detected in 11 (10.5%) differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinoma but correlated with high p16INK4A expression in only one case. Integration of viral DNA was never observed in differentiated vulvar intraepithelial neoplasia–associated squamous cell carcinomas, which suggests that a causal relationship of high-risk HPV in differentiated vulvar intraepithelial neoplasia–associated tumors is highly unlikely. The disease-specific survival of the differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinoma patients was significantly worse compared with patients with a usual vulvar intraepithelial neoplasia–associated tumor.

Conclusions: High-risk HPV is causally associated with the development of usual vulvar intraepithelial neoplasia associated squamous cell carcinomas, which comprise 19% of all vulvar squamous cell carcinomas, but not with differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinomas. Differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinomas have a significantly worse prognosis. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2061–7)
A Longitudinal Study of the Metabolic Syndrome and Risk of Postmenopausal Breast Cancer
Authors: Kabat Geoffrey C. , Kim Mimi , Chlebowski Rowan T. , Khandekar Janu , Ko Marcia G. , McTiernan Anne , Neuhouser Marian L. , Parker Donna R. , Shikany James M. , Stefanick Marcia L. , Thomson Cynthia A. , Rohan Thomas E.
Published: July 2009

The metabolic syndrome, characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension, is associated with increased risk of type 2 diabetes and coronary heart disease. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer; to date, however, no study has assessed the metabolic syndrome per se in relation to breast cancer risk. Furthermore, previous studies have relied only on baseline assessment of components of the syndrome. Therefore, we assessed the association of the metabolic syndrome with the risk of postmenopausal breast cancer among women in the 6% sample of subjects in the Women's Health Initiative clinical trial and the 1% sample of women in the observational study who had repeated measurements of the components of the syndrome during follow-up. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of breast cancer risk with the presence of the metabolic syndrome, as well as its components, at baseline and in time-dependent analyses. After exclusion of women with diabetes, among 4,888 women with baseline measurements, 165 incident cases of breast cancer were ascertained over a median of 8 years of follow-up. The presence of the metabolic syndrome at baseline was not associated with altered risk. Of the individual components measured at baseline, diastolic blood pressure showed a borderline positive association with breast cancer. In time-dependent covariate analyses, however, certain scenarios indicated a positive association between the metabolic syndrome and breast cancer, due primarily to positive associations with serum glucose, serum triglycerides, and diastolic blood pressure. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2046–53)
Association of Colorectal Cancer and Prostate Cancer and Impact of Radiation Therapy
Authors: Huo Dezheng , Hetzel Jeremy T. , Roy Hemant , Rubin David T.
Published: July 2009

To quantify the risk of prostate cancer after colorectal cancer and the risk of colorectal cancer after prostate cancer and to examine the impact of radiation therapy on subsequent cancer risk, we conducted retrospective cohort studies using data from the Surveillance, Epidemiology and End Results program from 1973 to 2005. Standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) were calculated, adjusting for age, ethnicity, and calendar year. The subsequent risk of developing a prostate cancer was significantly elevated in patients diagnosed with colon cancer before age 50 years (SIR, 1.38; 95% CI, 1.18-1.60). The risk of subsequent prostate cancer was decreased for men with rectal cancer who received radiation therapy (SIR, 0.57; 95% CI, 0.52-0.63). Interestingly, this beneficial effect of radiation therapy was only observed in the prostate-specific antigen (PSA) era (1988+). In addition, the prostate cancer cases developed in the radiation therapy group tended to have higher-grade, later-stage tumors, higher PSA levels, and worse survival than those developed in the nonradiation therapy group. In the cohort of prostate cancer patients, the risk of colon cancer was elevated in patients diagnosed with prostate cancer before age 50 years (SIR, 1.51; 95% CI, 1.03-2.20). In conclusion, a diagnosis of colon or prostate cancer in men of younger ages may be an indication for screening of prostate or colon cancer, respectively. The decreased prostate cancer risk in men who received radiation therapy for rectal cancer may be related to the use of PSA for prostate cancer screening or the cure of occult prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1979–85)
Stomach Carcinoma Incidence Patterns in the United States by Histologic Type and Anatomic Site
Authors: Wu Hongyu , Rusiecki Jennifer A. , Zhu Kangmin , Potter John , Devesa Susan S.
Published: July 2009

Background: Using data from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results program, we analyzed stomach carcinoma incidence patterns by both histologic type and anatomic site.

Methods: We calculated age-adjusted (2000 U.S. standard) rates for 1978 to 2005, and for five time periods from 1978-1983 through 2001-2005 according to histologic type and anatomic site, separately and jointly. We also analyzed rates by race, gender, and age group.

Results: During 1978 to 2005, more than 54,000 stomach carcinoma cases were diagnosed among residents of the nine Surveillance, Epidemiology, and End Results areas. Total stomach carcinoma rates declined by 34% from the 1978-1983 to the 2001-2005 time periods. By histologic type, intestinal rates decreased consistently, whereas those for diffuse rates increased through 2000 and declined in recent years. By anatomic site, cardia rates increased during earlier years and then decreased, whereas rates for all other sites declined. When considered jointly by histologic type and anatomic site, intestinal carcinoma rates decreased for all sites except the cardia; diffuse rates increased through 2000 and decreased in recent years for all sites except the overlapping/nonspecified sites. Both diffuse and intestinal rates were lowest among whites, intermediate among blacks, and highest among the other, primarily Asian, races, with only modest gender differences for the diffuse type. In contrast, cardia carcinoma rates were highest among whites and were notably higher among males, especially whites among whom the male/female rate ratio was five to one.

Conclusions: Stomach carcinoma incidence patterns differ by histologic type, anatomic site, race, gender, and age, suggesting that etiologic heterogeneity should be pursued in future research. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1945–52)
Increased Risk of Lymphoid Neoplasms in Patients with Philadelphia Chromosome–Negative Myeloproliferative Neoplasms
Authors: Vannucchi Alessandro M. , Masala Giovanna , Antonioli Elisabetta , Chiara Susini Maria , Guglielmelli Paola , Pieri Lisa , Maggi Laura , Caini Saverio , Palli Domenico , Bogani Costanza , Ponziani Vanessa , Pancrazzi Alessandro , Annunziato Francesco , Bosi Alberto
Published: July 2009

Association of myeloproliferative neoplasm (MPN) with lymphoproliferative neoplasm (LPN) has been occasionally reported. The aim of this study, which included 353 patients with polycythemia vera and 467 with essential thrombocythemia, was to assess whether the risk of developing LPN is increased in MPN patients. Expected numbers of LPN incident cases were calculated based on 5-year age group, gender, and calendar time–specific cancer incidence rates in the general population of the same area. Standardized incidence ratios were computed to estimate the relative risk of developing LPN. Analyses were carried out for the whole series and then separately for essential thrombocythemia and polycythemia vera, gender, and JAK2V617F genotype. With 4,421 person-years, we found 11 patients developing LPN, including four chronic lymphocytic leukemias, five non–Hodgkin's lymphomas, and two plasma cell disorders, after a median interval time of 68 months from MPN diagnosis. Cumulative risk to develop LPN at 5 and 10 years was 0.93% (95% confidence interval, 0.39-2.22) and 2.96% (95% confidence interval, 1.52-5.72), respectively. There was a 3.44-fold increased risk of LPN compared with the general population, ranging from 2.86 for plasma cell disorder to 12.42 for chronic lymphocytic leukemia; the risk was significantly increased in JAK2V617F mutated patients (5.46-fold) and in males (4.52-fold). The JAK2V617F mutation was found in lymphoid tumor cells in two of three cases evaluated, indicating that, in some patients, LPN originated in a JAK2V617F mutated common lymphoid-myeloid hematopoietic progenitor cell. We conclude that the risk of developing LPN is significantly increased in MPN patients compared with the general population. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2068–73)
Refining Molecular Pathways Leading to Calcific Aortic Valve Stenosis by Studying Gene Expression Profile of Normal and Calcified Stenotic Human Aortic Valves
Authors: Bossé Yohan , Miqdad Ahmed , Fournier Dominique , Pépin Andrée , Pibarot Philippe , Mathieu Patrick
Published: July 2009

Background—

Calcific aortic valve stenosis (AS) is a major societal and economic burden that is rising after the current shift toward an older population. Understanding the pathobiology of AS is crucial to implementing better preventive and therapeutic options. Research conducted during the past decade clearly points to active molecular and cellular processes involved in disease pathogenesis. However, no genomic approaches were used to identify genes and pathways that are differentially regulated in aortic valves of patients with and without AS.

Methods and Results—

A large-scale quantitative measurements of gene expression was performed on 5 normal and 5 AS valves using Affymetrix GeneChips. A total of 409 and 306 genes were significantly up- and downregulated in AS valves, respectively. The 2 most highly upregulated genes were matrix metalloproteinase 12 and chitinase 3-like 1. The upregulation of these 2 biologically relevant genes in AS was validated by real-time polymerase chain reaction in 38 aortic valves (12 normal and 26 AS). To provide a global biological validation of the whole-genome gene expression analysis, the microarray experiment was repeated in a second set of aortic valves with (n=5) or without (n=5) AS. There was an overrepresentation of small
P
values among genes claimed significant in the first microarray experiment. A total of 223 genes were replicated (
P
<0.05 and fold change >1.2), including matrix metalloproteinase 12 and chitinase 3-like 1.

Conclusions—

This study reveals many unrecognized genes potentially implicated in the pathogenesis of AS. These new genes were overlaid on known pathological pathways leading to AS to refine our molecular understanding of this disease.
Reform of the Administration of Justice System at the United Nations
Authors: Hwang Phyllis
Published: July 2009

For nearly six decades, the administration of justice system at the United Nations has been comprised primarily of the Joint Appeals Boards, the Joint Disciplinary Committees and the UN Administrative Tribunal. In July 2009, these bodies will be dismantled and replaced with an entirely new system. This article will first describe the basic features of the administration of justice system at the United Nations that existed prior to July 2009. It will then review the history of efforts to reform the system, leading up to the proposals of the Redesign Panel issued in August 2006. It will also look at similar initiatives implemented by other intergovernmental organizations to reform their own internal justice systems in recent years. Finally, the article will highlight the main elements of the new administration of justice system, as approved by the General Assembly in 2007-2008, and examine its implications for UN staff members in the future.
Changes of Variability in Response to Increasing Greenhouse Gases. Part II: Hydrology
Authors: Wetherald Richard T.
Published: July 2009

This paper examines hydrological variability and its changes in two different versions of a coupled ocean–atmosphere general circulation model developed at the National Oceanic and Atmospheric Administration/Geophysical Fluid Dynamics Laboratory and forced with estimates of future increases of greenhouse gas and aerosol concentrations. This paper is the second part, documenting potential changes in variability as greenhouse gases increase. The variance changes are examined using an ensemble of 8 transient integrations for an older model version and 10 transient integrations for a newer model. Monthly and annual data are used to compute the mean and variance changes. Emphasis is placed on computing and analyzing the variance changes for the middle of the twenty-first century and compared with those found in the respective control integrations.

The hydrologic cycle intensifies because of the increase of greenhouse gases. In general, precipitation variance increases in most places. This is the case virtually everywhere the mean precipitation rate increases and many places where the precipitation decreases. The precipitation rate variance decreases in the subtropics, where the mean precipitation rate also decreases. The increased precipitation rate and variance, in middle to higher latitudes during late fall, winter, and early spring leads to increased runoff and its variance during that period.

On the other hand, the variance changes of soil moisture are more complicated, because soil moisture has both a lower and upper bound that tends to reduce its fluctuations. This is particularly true in middle to higher latitudes during winter and spring, when the soil moisture is close to its saturation value at many locations. Therefore, changes in its variance are limited. Soil moisture variance change is positive during the summer, when the mean soil moisture decreases and is close to the middle of its allowable range. In middle to high northern latitudes, an increase in runoff and its variance during late winter and spring plus the decrease in soil moisture and its variance during summer lend support to the hypothesis stated in other publications that a warmer climate can cause an increasing frequency of both excessive discharge and drier events, depending on season and latitude.
Evaluating the Uncertainty Induced by the Virtual Salt Flux Assumption in Climate Simulations and Future Projections
Authors: Yin Jianjun , Stouffer Ronald J. , Spelman Michael J. , Griffies Stephen M.
Published: July 2009

The unphysical virtual salt flux (VSF) formulation widely used in the ocean component of climate models has the potential to cause systematic and significant biases in modeling the climate system and projecting its future evolution. Here a freshwater flux (FWF) and a virtual salt flux version of the Geophysical Fluid Dynamics Laboratory Climate Model version 2.1 (GFDL CM2.1) are used to evaluate and quantify the uncertainties induced by the VSF formulation. Both unforced and forced runs with the two model versions are performed and compared in detail. It is found that the differences between the two versions are generally small or statistically insignificant in the unforced control runs and in the runs with a small external forcing. In response to a large external forcing, however, some biases in the VSF version become significant, especially the responses of regional salinity and global sea level. However, many fundamental aspects of the responses differ only quantitatively between the two versions. An unexpected result is the distinctly different ENSO responses. Under a strong external freshwater forcing, the great enhancement of the ENSO variability simulated by the FWF version does not occur in the VSF version and is caused by the overexpansion of the top model layer. In summary, the principle assumption behind using virtual salt flux is not seriously violated and the VSF model has the ability to simulate the current climate and project near-term climate evolution. For some special studies such as a large hosing experiment, however, both the VSF formulation and the use of the FWF in the geopotential coordinate ocean model could have some deficiencies and one should be cautious to avoid them.
Role of Subsurface Physics in the Assimilation of Surface Soil Moisture Observations
Authors: Kumar Sujay V. , Reichle Rolf H. , Koster Randal D. , Crow Wade T. , Peters-Lidard Christa D.
Published: July 2009

Root-zone soil moisture controls the land–atmosphere exchange of water and energy, and exhibits memory that may be useful for climate prediction at monthly scales. Assimilation of satellite-based surface soil moisture observations into a land surface model is an effective way to estimate large-scale root-zone soil moisture. The propagation of surface information into deeper soil layers depends on the model-specific representation of subsurface physics that is used in the assimilation system. In a suite of experiments, synthetic surface soil moisture observations are assimilated into four different models [Catchment, Mosaic, Noah, and Community Land Model (CLM)] using the ensemble Kalman filter. The authors demonstrate that identical twin experiments significantly overestimate the information that can be obtained from the assimilation of surface soil moisture observations. The second key result indicates that the potential of surface soil moisture assimilation to improve root-zone information is higher when the surface–root zone coupling is stronger. The experiments also suggest that (faced with unknown true subsurface physics) overestimating surface–root zone coupling in the assimilation system provides more robust skill improvements in the root zone compared with underestimating the coupling. When CLM is excluded from the analysis, the skill improvements from using models with different vertical coupling strengths are comparable for different subsurface truths. Last, the skill improvements through assimilation were found to be sensitive to the regional climate and soil types.