bluuebunny/crossref_metadata_2025 huggingface dataset:
Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents
Authors: Mineur Pierre , Colige Alain C. , Deroanne Christophe. F. , Dubail Johanne , Kesteloot Frédéric , Habraken Yvette , Noël Agnès , Vöö Stefan , Waltenberger Johannes , Lapière Charles M. , Nusgens Betty V. , Lambert Charles A.
Published: December 2007

Ultraviolet B and genotoxic drugs induce the expression of a vascular endothelial growth factor A (VEGF-A) splice variant (VEGF111) encoded by exons 1–4 and 8 in many cultured cells. Although not detected in a series of normal human and mouse tissue, VEGF111 expression is induced in MCF-7 xenografts in nude mice upon treatment by camptothecin. The skipping of exons that contain proteolytic cleavage sites and extracellular matrix–binding domains makes VEGF111 diffusible and resistant to proteolysis. Recombinant VEGF111 activates VEGF receptor 2 (VEGF-R2) and extracellularly regulated kinase 1/2 in human umbilical vascular endothelial cells and porcine aortic endothelial cells expressing VEGF-R2. The mitogenic and chemotactic activity and VEGF111's ability to promote vascular network formation during embyonic stem cell differentiation are similar to those of VEGF121 and 165. Tumors in nude mice formed by HEK293 cells expressing VEGF111 develop a more widespread network of numerous small vessels in the peritumoral tissue than those expressing other isoforms. Its potent angiogenic activity and remarkable resistance to proteolysis makes VEGF111 a potential adverse factor during chemotherapy but a beneficial therapeutic tool for ischemic diseases.
MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis
Authors: Kang Jihong , Rivest Serge
Published: December 2007

Increasing evidence suggests that neurotoxicity of secreted superoxide dismutase 1 (SOD1) mutants is associated with amyotrophic lateral sclerosis (ALS). We show here that mutant SOD1 protein activates microglia via a myeloid differentiation factor 88 (MyD88)–dependent pathway. This inflammatory response is also associated with a marked recruitment of bone marrow–derived microglia (BMDM) in the central nervous system. We then generated chimeric SOD1G37R and SOD1G93A mice by transplantation of bone marrow (BM) cells from MyD88-deficient or green fluorescent protein (GFP)–expressing mice. SOD1G37R mice receiving MyD88−/− BM cells exhibit a significantly earlier disease onset and shorter lifespan compared with mice transplanted with control GFP cells. This compelling beneficial effect of MyD88-competent BMDM is a previously unrecognized natural innate immune mechanism of neuroprotection in a mouse model of late-onset motor neuron disease.
Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents down-regulation by PKC
Authors: Solan Joell L. , Marquez-Rosado Lucrecia , Sorgen Paul L. , Thornton Perry J. , Gafken Philip R. , Lampe Paul D.
Published: December 2007

Phosphorylation at unspecified sites is known to regulate the life cycle (assembly, gating, and turnover) of the gap junction protein, Cx43. In this paper, we show that Cx43 is phosphorylated on S365 in cultured cells and heart tissue. Nuclear magnetic resonance structural studies of the C-terminal region of Cx43 with an S365D mutation indicate that it forms a different stable conformation than unphosphorylated wild-type Cx43. Immunolabeling with an antibody specific for Cx43 phosphorylated at S365 shows staining on gap junction structures in heart tissue that is lost upon hypoxia when Cx43 is no longer specifically localized to the intercalated disk. Efficient phosphorylation at S368, an important Cx43 channel regulatory event that increases during ischemia or PKC activation, depends on S365 being unphosphorylated. Thus, phosphorylation at S365 can serve a “gatekeeper” function that may represent a mechanism to protect cells from ischemia and phorbol ester-induced down-regulation of channel conductance.
Effects of Fin Shapes and Arrangements on Heat Transfer for
Impingement∕Effusion Cooling with Crossflow
Authors: Hong Sung Kook , Rhee Dong-Ho , Cho Hyung Hee
Published: December 2007

The present paper has investigated the effects of fins on the flow and heat∕mass transfer characteristics for the impingement∕effusion cooling with crossflow. The circular or rectangular fins are installed between two perforated plates, and the crossflow occurs between these two plates. The crossflow blowing ratio is varied from 0.5 to 1.5 for a fixed jet Reynolds number of 10,000. A naphthalene sublimation method is used to obtain local heat∕mass transfer coefficients on the effusion plate. A numerical calculation is also performed to investigate the flow characteristics. The flow and heat∕mass transfer characteristics are changed significantly due to the installation of fins. In the injection hole region, the wall jet spreads more widely than in the case without fins because the fins prevent the wall jet from being swept away by the crossflow. In the effusion hole region, a higher heat∕mass transfer coefficient is obtained due to the flow disturbance and acceleration by the fin. As the blowing ratio increases, the effect of fins against the crossflow becomes more significant and subsequently the higher average heat∕mass transfer coefficients are obtained. In particular, the cases with rectangular fins show an approximately 40–45% enhancement at the high blowing ratio of M=1.5. However, the increase in the blockage effect results in increased pressure loss in the channel.
Discrete Green’s Function Measurements in a Serpentine Cooling Passage
Authors: Booten Charles W. , Eaton John K.
Published: December 2007

The inverse discrete Green’s function (IDGF) is a heat transfer coefficient that is valid for arbitrarily complex thermal boundary conditions. It was measured using a rapid experimentation technique in a generic serpentine turbine-blade cooling passage with rib turbulators for Reynolds numbers from 15,000 to 55,000. The model was designed to adhere closely to industry design practice. There were four square cross-section passages with ribs on two opposing walls at 45deg to the main flow. The rib pitch-to-height ratio was 8.5:1 and the blockage ratio was 0.1. The IDGF was measured with an element length of one rib pitch and was used to determine Nusselt numbers that were then compared to the literature. An increase in Nusselt number over thermally fully developed pipe flow of 2.5–3.0 is common in the literature and was consistent with the results in this work. The results showed that the heat transfer coefficient in such complex passages is weakly affected by the thermal boundary condition, which simplifies measurement of this quantity.
Optically
Based Rapid Heat Transfer Measurements in Complex Internal
Flows
Authors: Booten Charles
W. , Eaton John
K.
Published: December 2007

An optically based technique was developed that involves fabrication of a thin-walled plastic model with laser heating applied to a small section of the outer surface. The heat flux distribution applied to the model by the laser was measured first using a short-duration, transient experiment. The external temperature distribution was then recorded using infrared thermography with steady laser heating. The measured heat flux and temperature distributions were used as thermal boundary conditions in a finite-element code to solve an inverse heat conduction problem for the heat transfer coefficient on the internal passage wall. Hydrodynamically fully developed turbulent flow in a round tube was used as a test case for the development of the new optical method. The Reynolds numbers used were 30,000 and 60,000. This flow was chosen because accurate computational tools were available to calculate the internal heat transfer coefficient for a variety of thermal boundary conditions. In addition, this geometry simplified both the model fabrication and the implementation of a finite-element model for the inverse heat conduction problem. Heat transfer coefficient measurements agreed with numerical simulations and semi-analytical solutions within 1.5% and 8.5% for the low and high Reynolds numbers, respectively. Additional simulations suggest that the method can be accurate with thermal boundary conditions more complex than in these experiments.
Effective Conductivity of a Composite in a Primitive Tetragonal Lattice of Highly Conducting Spheres in Resistive Thermal Contact With the Isolating Matrix
Authors: Filip Cristina , Garnier Bertrand , Danes Florin
Published: December 2007

A state-of-the-art study and a physical and numerical 3D finite element study of anisotropic conduction through composites filled with isometric inclusions of different conductivity were performed by modeling the longitudinal conduction across a tetragonal lattice of spheres in imperfect contact with the surrounding matrix. In dimensionless variables, the effective conductivity E is expressible as a function of a geometrical parameter B, reflecting the relative thickness of the gap between spheres, the Kapitza resistance C of the contact inclusion/matrix, and the relative resistivity D of the filler. The computation of some 600 E values at some 25 levels of the factors B, C, and D allows one to find some features, such as the leading role of the factor whose value is the highest of three, the low effect of the interactions between factors, the imperfect equivalence of the effects of the three factors, the slow and linear E dependence on the second and third greatest factor, and finally, the asymptotically exact linear relationship between E and the logarithmated sum of factors, with a slope depending only slightly on the relative magnitudes of factors.
A Coupled Map Lattice Model of Flow Boiling in a Horizontal Tube
Authors: Ghoshdastidar P. S. , Chakraborty Indrajit
Published: December 2007

In this work laminar, stratified flow boiling of water is simulated qualitatively by the coupled map lattice (CML) method. The liquid is entering a constant wall temperature horizontal tube (Tw>Tsat at pentrance) in a subcooled condition. A CML is a dynamical system with discrete-time, discrete-space, and continuous states. The procedure basically consists of the following steps: (i) Choose a set of macroscopic variables on a lattice; (ii) decompose the problem into independent components, such as convection, diffusion, phase change, and so on; (iii) replace each component by a simple parallel dynamics on a lattice; and (iv) carry out each unit dynamics successively in each time step until some termination criterion is satisfied. In the present problem, the termination criterion is the laminar-turbulent transition, and hence, the results do not correspond to the steady state. The present modeling by CML is based on the assumption that the flow boiling is governed by (i) nucleation from cavities on the heated surface and migration of vapor into the core, (ii) forced convection, and (iii) phase change in the fluid bulk and mixing. The stirring action of the bubbles is modeled by increasing the fluid momentum and thermal diffusivities by an enhancement factor. The results show that the CML has been able to model flow boiling in a realistic manner.
Multiscale fracture analysis along the French chalk coastline for investigating erosion by cliff collapse
Authors: Genter A. , Duperret A. , Martinez A. , Mortimore R. N. , Vila J-L.
Published: December 2007

Coastal cliffs of Upper Normandy and Picardy are eroded by cliff collapses of various sizes. This paper presents a multi-scale analysis of the pre-existing fractures embedded within the Cretaceous chalk. About 20 representative sites equally spaced along the 120km long coastal section were analysed and compared to a continuous structural analysis of the coast derived from aerial photographs taken in 1986. Ancient collapses interpreted on the aerial photos were compared to the pre-existing fracture content. Regional faults, pre-1986 collapse location and fracture density are spatially correlated. However, recent collapses observed on the field between 1998 and 2001 did not systematically correlate to the pre-existing fracture occurrence and therefore, there is no clear link between recent collapse and the regional faults.
Prediction of nearshore wave energy distribution by analysis of numerical wave model output, East Sussex coastline, UK
Authors: Mitchell S. B. , Pope D. J.
Published: December 2007

Prediction of wave energy distribution in coastal areas is necessary if an assessment of the likelihood of cliff collapse is to be undertaken. Use has been made of numerical modelling to predict relative wave heights along the chalk cliff coastline of East Sussex between Brighton and Eastbourne, UK. In this study, wave modelling has been undertaken using the University of Delaware REFDIF-1 software with a 100m mesh size to predict nearshore wave heights for boundary unit wave height conditions from a range of different incident directions. The results from this wave modelling have been combined with the frequency distribution of incident waves obtained from analysis of time series of 12 years of hindcast wave data in the English Channel, obtained from the UK Meteorological Office. The resulting distribution of nearshore wave heights is presented as a surrogate for the distribution of wave energy over the 12-year period. Some concern exists about the quality of the output data, in particular of the effect of the relatively coarse bathymetry grid used for the model. Some wave focusing is evident from the model output, caused by the presence of local shoals in the model grid, leading to a ‘banding’ effect in the model output. Some suggestions are made for the improvement of the modelling scheme, including the use of finer mesh size, bathymetric smoothing and the use of a spectral model such as REFDIF-S.
Quantification of the Normandy and Picardy chalk cliff retreat by photogrammetric analysis
Authors: Costa S. , Delahaye D. , Freiré-Diaz S. , Di Nocera L. , Davidson R. , Plessis E.
Published: December 2007

The chalk cliffs of Normandy and Picardy are retreating rapidly and approaching the built-up areas located near the shore. Previous studies of cliff retreat in this area suffer from a large margin of error (absolute error in cliff position is ±7 m) due to the techniques and methods used. This paper presents a recent study which aims to quantify the chalk cliff retreat between 1966 and 1995 by means of photogrammetric analysis. In addition to the very high accuracy of the results (absolute error in cliff position is ±0.3 m), this technique gives geo-referenced numeric data allowing the creation of a geographical databank intended to become a tool for hazard management in coastal zones. Three scales of analysis have been used: a retreat value per hydro-sedimentary cell, per sub-cell and one every 50m. These scales show that this regressive dynamic is spatially very variable. However, three zones of distinct retreat rates are apparent. These appear to be linked with the lithological characteristics of the chalk. Furthermore, the quantification associated with the flint content of the cliff allows an assessment of the flint shingle provision from the cliff to the shore.
Incompressible viscous formulations for deformation and yielding of the lithosphere
Authors: Moresi L. , Mühlhaus H.-B. , Lemiale V. , May D.
Published: December 2007

In models of crustal deformation at a scale of a few tens of kilometres, it is appropriate to use a Mohr–Coulomb yield criterion for lithospheric failure based on the idea that frictional slip occurs on whichever one of many randomly oriented planes happens to be favourably oriented with respect to the stress field. The Drucker–Prager yield criterion has very similar characteristics to the Mohr–Coulomb criterion but is more straightforward to implement, particularly in the context of large-scale fluid-mechanical deformation of the coupled system of mantle, lithosphere and crust. As such models become more sophisticated it is important to be able to use whichever failure model is appropriate to a given part of the system. We have therefore developed a way to represent Mohr–Coulomb failure within the mathematical framework used by mantle-convection fluid dynamics codes.

The new formulation is based on the conceptual picture of lithospheric failure incorporated in the Anderson model of fault development and reproduces shear band angles predicted by this model. We use an transversely isotropic viscous rheology (a different viscosity for pure shear to that for simple shear) to define a preferred plane for slip to occur given the local stress field. The simple-shear viscosity and the deformation can then be iterated to ensure that the yield criterion is always satisfied. We assume the Boussinesq approximation can be applied in the model – neglecting any effect of dilatancy on the stress field. An additional criterion is required to ensure that deformation occurs along the plane aligned with maximum shear strain rate rather than the perpendicular plane, which is formally equivalent in any symmetric formulation.

We compare the behaviour of this formulation to the Drucker–Prager failure model for two-dimensional (2D) layered brittle–ductile systems. The pattern of shear bands is found to be quite similar from each model, although some differences are seen in the characteristic spacings for ‘equivalent’ values of the material properties. In 3D similar patterns are seen but are modulated by additional 3D structure.
Early Cretaceous motion of Flemish Cap with respect to North America: implications on the formation of Orphan Basin and SE Flemish Cap–Galicia Bank conjugate margins
Authors: Sibuet J.-C. , Srivastava S. P. , Enachescu M. , Karner G. D.
Published: December 2007

Bouguer gravity anomalies together with deep seismic reflection and magnetic data on both sides of the North Atlantic are used to locate the hinge zones of the Flemish Cap and Galicia Bank within the Iberian and North American plates, regions across which there were abrupt changes in lithospheric extension. The characteristic shape and alignment of these hinge zones suggest that they were conjugate features generated during chrons M25–M0 (Late Jurassic–Early Aptian) around a distally located Euler pole of rotation. Rifting between Iberia and North America involved these two larger plates and the two smaller microplates – the Flemish Cap and Galicia Bank microplates. The motion of the microplates, which were adjacent to Eurasia, was much more complex than those of the larger plates. The motion between the microplates from chron M25 or older to chron M0 was complicated by the fact that they remained attached to each other for most of the time when regions to the south were rifting apart. As a result, continental regions landward of these segments were subjected to extension that created the Orphan and Flemish Pass basins on the North American side and the Galicia Interior Basin on the Iberian side. By comparing the hinge zones delineated off Galicia Bank and Flemish Cap using the Bouguer anomalies, we were able to infer that Flemish Cap rotated approximately 43° relative to Galicia Bank and Iberia, and moved 200–300 km SE with respect to North America.

Such motions of Flemish Cap and Galicia Bank agree remarkably well with extensional episodes deduced from industry multichannel seismic reflection data acquired in the Orphan Basin. Normal fault orientations identified in the West Orphan Basin trend N020° and are approximately perpendicular to the flow lines of our proposed Flemish Cap–North American motion during the M25–M0 period, which provides an independent constraint on our proposed kinematic model. Therefore, extensional events affected not only the Galicia Bank–Flemish Cap conjugate margins but also the Galicia Interior and Orphan Basins, and need to be taken into account in any assessment of the geological development of the Iberian and North American continental margins.
Roles of lithospheric strain softening and heterogeneity in determining the geometry of rifts and continental margins
Authors: Huismans R. S. , Beaumont C.
Published: December 2007

Plane strain thermo-mechanical finite-element model experiments are used to investigate the effects of frictional–plastic strain softening and inherited weakness on the style of lithospheric extension. The model results are compared with the Newfoundland–Iberia conjugate rifted margins with the goal of understanding the lithospheric properties that controlled their evolution during rifting. Our proposition is that coupling between the plastic–viscous layering, acting together with frictional–plastic strain softening localized on inherited weak heterogeneities, can explain the initial wide rift and distributed rift basins that are later abandoned in favour of a narrow rift in which mantle lithosphere is exhumed to the surface. The models comprise uniform composition viscous and plastic layers in which focused deformation is nucleated on either a single weak ‘seed’ or a statistical white noise distribution of inherited strain. Strain softening of frictional–plastic layers acts as a positive feedback mechanism that creates localized shear zones from the inherited weak heterogeneities. The sensitivity of deformation to the choice of softening parameters and the type of inherited noise is examined in cases where the deeper part of the crust is either weak or strong.

Lithosphere-scale models with a single weak seed exhibit a range of asymmetric and symmetric rifting modes that are mostly determined by the feedback between two primary controls, coupling between the plastic and viscous layers and strain softening. Decreasing and increasing the rifting velocity can change the mode, and asymmetry is strongest in models with low rifting velocities and a strong lower crust. Analysis of equivalent simple-bonded plastic–viscous two-layer models using the minimum rate of dissipation principle demonstrates that the mode selected depends on the division of the dissipation between the layers. Criteria developed on minimizing the total dissipation show how mode selection changes with increasing viscosity, or rifting velocity, from the: asymmetric plug or half-graben (AP) mode; through the symmetric plug or graben (PS) mode, to the distributed pure shear (PS) mode. Numerical models confirm these results.

Models with statistical white-noise-inherited strain have similar modes to those with a single seed. In addition, modes with multiple sets of shear zones develop in the plastic layer for a range of intermediate parameter combinations. We believe that distributed noise in combination with a weak lower crust and slow extension can produce model results in accord with general features of the Newfoundland–Iberia conjugate margins; an initially distributed wide rift mode, followed by a late-stage narrow rift with a significant component of mantle exhumation.
A Longitudinal Swedish Study on Screening for Squamous Cell Carcinoma and Adenocarcinoma: Evidence of Effectiveness and Overtreatment
Authors: Gunnell Anthony S. , Ylitalo Nathalie , Sandin Sven , Sparén Pär , Adami H.-O. , Ripatti Samuli
Published: December 2007

Background: Organized Papanicolaou (Pap) screening has markedly reduced the incidence of cervical squamous cell carcinoma (SCC). However, the potential for overtreatment of precursor lesions is quite high for SCC, and the effectiveness of Pap screening for prevention of cervical adenocarcinoma is questionable.

Methods: Using the nationwide, virtually complete Swedish Cancer Register, we analyzed standardized incidence rates for SCC in situ (CIS), SCC, adenocarcinoma in situ (AIS) and adenocarcinoma, between 1968 and 2002. For each county, we calculated Spearman correlations between incidence of in situ lesions and incidence of invasive cancer, 5, 10, and 15 years later. We also used generalized estimating equation (GEE) models to compare adjusted estimates for associations between in situ incidences and invasive carcinomas over counties.

Results: The overall decrease in SCC incidence in Sweden following the introduction of cervical screening confirms the beneficial nature of cervical screening on SCC incidence over the last 30 years. A similar benefit was not apparent for adenocarcinoma. GEE estimates for the relative change in SCC for an increase of 100 CIS cases per 100,000 women-years were 1.05 for the 5-year and 1.02 for the 10-year lag periods. For adenocarcinoma and AIS, similar analyses gave corresponding estimates of 1.17 for the 5-year and 1.08 for the 10-year lag periods. The lack of an inverse correlation suggests that increased reported incidence of CIS in certain counties did not forecast a reduction in SCC for those counties.

Conclusion: Our data confirm the effectiveness of Pap smear screening in reducing the incidence of SCC, but suggest no clear benefit on adenocarcinoma. Our data also suggest that relaxed histopathologic criteria for diagnosis of cervical CIS may increase its recorded incidence with no measurable benefit in the reduction of invasive cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2641–8)
Plasma Isoflavones and Fibrocystic Breast Conditions and Breast Cancer Among Women in Shanghai, China
Authors: Lampe Johanna W. , Nishino Yoshikazu , Ray Roberta M. , Wu Chunyuan , Li Wenjin , Lin Ming-Gang , Gao Dao Li , Hu Yongwei , Shannon Jackilen , Stalsberg Helge , Porter Peggy L. , Frankenfeld Cara L. , Wähälä Kristiina , Thomas David B.
Published: December 2007

Background: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions.

Materials and Methods: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173).

Results: Isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (Ptrend < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone.

Conclusion: Isoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2579–86)
Meat and Meat-Mutagen Intake and Pancreatic Cancer Risk in the NIH-AARP Cohort
Authors: Stolzenberg-Solomon Rachael Z. , Cross Amanda J. , Silverman Debra T. , Schairer Catherine , Thompson Frances E. , Kipnis Victor , Subar Amy F. , Hollenbeck Albert , Schatzkin Arthur , Sinha Rashmi
Published: December 2007

Meat intake, particularly red meat, has been positively associated with pancreatic cancer in some epidemiologic studies. Detailed meat-cooking methods and related mutagens formed in meat cooked at high temperatures have not been evaluated prospectively as risk factors for this malignancy. We investigated the association between meat, meat-cooking methods, meat-mutagen intake, and exocrine pancreatic cancer in the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study cohort of 537,302 individuals, aged 50 to 71 years, with complete baseline dietary data (1995-1996) ascertained from a food frequency questionnaire. A meat-cooking module was completed by 332,913 individuals 6 months after baseline. During 5 years of follow-up, 836 incident pancreatic cancer cases (555 men, 281 women) were identified. Four hundred and fifty-nine cases had complete meat module data. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Total, red, and high-temperature cooked meat intake was positively associated with pancreatic cancer among men (fifth versus first quintile: HR, 1.41, 95% CI, 1.08-1.83, P trend = 0.001; HR, 1.42, 95% CI, 1.05-1.91, P trend = 0.01; and HR, 1.52, 95% CI, 1.12-2.06, P trend = 0.005, respectively), but not women. Men showed significant 50% increased risks for the highest tertile of grilled/barbecued and broiled meat and significant doubling of risk for the highest quintile of overall meat-mutagenic activity (P trends < 0.01). The fifth quintile of the heterocyclic amine, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline intake showed a significant 29% (P trend = 0.006) increased risk in men and women combined. These findings support the hypothesis that meat intake, particularly meat cooked at high temperatures and associated mutagens, may play a role in pancreatic cancer development. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2664–75)
Decreasing Trend of Esophageal Adenocarcinoma in Hong Kong
Authors: Yee Yuk Kei , Cheung TK , Chan Annie On On , Yuen MF , Wong Benjamin C.Y.
Published: December 2007

Background: The incidence of esophageal adenocarcinoma was increasing in the Western Europe and United States, but not in East Asian countries. Population based study on the trend of esophageal adenocarcinoma in Hong Kong was not available.

Materials and Methods: Population-based data of Hong Kong Cancer Registry from 1984 to 2003 were used. Cases were grouped into four 5-year periods. Average age standardized rate (WSR) of each period was calculated by averaging the WSR of the 5 years in each period, basing on the world standard population, with adjustment made for cases with missing histology.

Results: 10,751 new cases of esophageal neoplasm were studied (8,637 males and 2,114 females). Esophageal adenocarcinoma declined among both males and females, with the total number decreased from 224 in 1984 to 1988 to 131 in 1998 to 2003. WSR decreased from 1.10 of 100,000 in 1984 to 1988 to 0.34 of 100,000 in 1998 to 2003. The decline was faster than that for esophageal squamous cell carcinoma so that the relative ratio of esophageal adenocarcinoma decreased from 11.7% in 1984 to 1988 to 6.4% in 1998 to 2003.

Conclusions: The incidence of esophageal adenocarcinoma and ratio of esophageal adenocarcinoma versus esophageal squamous cell carcinoma decreased in Hong Kong. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2637–40)
Highly Methylated Genes in Colorectal Neoplasia: Implications for Screening
Authors: Zou Hongzhi , Harrington Jonathan J. , Shire Abdirashid M. , Rego Rafaela L. , Wang Liang , Campbell Megan E. , Oberg Ann L. , Ahlquist David A.
Published: December 2007

Discriminant markers are required for accurate cancer screening. We evaluated genes frequently methylated in colorectal neoplasia to identify the most discriminant ones. Four genes specifically methylated in colorectal cancer [bone morphogenetic protein 3 (BMP3), EYA2, aristaless-like homeobox-4 (ALX4), and vimentin] were selected from 41 candidate genes and evaluated on 74 cancers, 62 adenomas, and 70 normal epithelia. Methylation status was analyzed qualitatively and quantitatively and confirmed by bisulfite genomic sequencing. Effect of methylation on gene expression was evaluated in five colon cancer cell lines. K-ras and BRAF mutations were detected by sequencing. Methylation of BMP3, EYA2, ALX4, or vimentin was detected respectively in 66%, 66%, 68%, and 72% of cancers; 74%, 48%, 89%, and 84% of adenomas; and 7%, 5%, 11%, and 11% of normal epithelia (P < 0.01, cancer or adenoma versus normal). Based on area under the curve analyses, discrimination was not significantly improved by combining markers. Comethylation was frequent (two genes or more in 72% of cancers and 84% of adenomas), associated with proximal neoplasm site (P < 0.001), and linked with both BRAF and K-ras mutations (P < 0.01). Cell line experiments supported silencing of expression by methylation in all four study genes. This study shows BMP3, EYA2, ALX4, and vimentin genes are methylated in most colorectal neoplasms but rarely in normal epithelia. Comethylation of these genes is common, and pursuit of complementary markers for methylation-negative neoplasms is a rational strategy to optimize screening sensitivity. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2686–96)
Changes in Breast Cancer Incidence Rates in the United States by Histologic Subtype and Race/Ethnicity, 1995 to 2004
Authors: Li Christopher I. , Daling Janet R.
Published: December 2007

Breast cancer incidence rates rose throughout the 1980s and 1990s in the United States but have recently declined through 2004. Studies reporting this decline primarily attribute it to the sharp decline in menopausal hormone use following publication of the Women's Health Initiative trial results. However, they have not stratified rates by either histologic type or race/ethnicity, which could further inform contributors to these trends. Using data from 13 cancer registries that participate in the Surveillance, Epidemiology, and End Results program, we evaluated annual percent changes (APC) in breast cancer incidence rates from 1995 to 2004 by histologic type and race/ethnicity for intervals identified using joinpoint regression. Invasive ductal carcinoma and invasive lobular carcinoma incidence rates fell steadily from 1998 to 2004 [APC, −3.07% (95% confidence interval, −4.10 to −2.02) and APC, −3.18% (95% confidence interval, −5.18 to −1.03), respectively]. Declines in rates of breast cancer overall and invasive ductal carcinoma were primarily limited to women ≥50 years of age and to non-Hispanic whites and Asian/Pacific Islanders, and declines in rates of invasive lobular carcinoma were primarily limited to non-Hispanic whites. The majority of these declines began around 1998 and all began before 2002 when the Women's Health Initiative trial results were published; thus, the abrupt decline in hormone therapy use starting in 2002 is unlikely to be primarily responsible for the recent decline in breast cancer rates. The declines observed thus far are likely attributable to saturation of screening, although further declines related to the widespread cessation of hormone use may follow. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2773–80)
Menopausal Hormone Therapy and Risk of Epithelial Ovarian Cancer
Authors: Rossing Mary Anne , Cushing-Haugen Kara L. , Wicklund Kristine G. , Doherty Jennifer A. , Weiss Noel S.
Published: December 2007

Substantial increase in the use of menopausal hormone therapy (HT) throughout the 1990s, followed by widespread discontinuation after the 2002 publication of the Women's Health Initiative findings, has resulted in large numbers of former HT users among U.S. women. However, few studies have examined whether ovarian cancer risk varies according to recency and duration of specific HT regimens. We assessed risk of epithelial ovarian cancer among users of unopposed estrogen (ET) and combined estrogen/progestogen (EPT). In a population-based study in Washington state, 812 women with ovarian cancer diagnosed in 2002 to 2005 and 1,313 controls were interviewed in person about the use of HT and other characteristics. Women who used a single form of therapy (ET or EPT) were compared with women who never used HT using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). Risk was increased among current or recent (within the last 3 years) users of ET with ≥5 years of use (ORs, 95% CIs: 1.6, 1.1-2.5 and 1.8, 0.8-3.7, respectively). Little increase in risk was noted among long-term ET users who discontinued use in the more distant past (OR, 1.2; 95% CI, 0.6-2.6). No increase in risk was noted among women who used only EPT, regardless of duration. Compared with women who never used HT, current users of EPT had an OR of 1.1 (95% CI, 0.8-1.5), and risk declined with increasing time since stopping; the OR was 0.7 (95% CI, 0.4-1.0) among women who had discontinued EPT within the last 3 years and 0.5 (95% CI, 0.3-0.7) among women who stopped at an earlier point. Long-term ET may be associated with an increased ovarian cancer risk that wanes after use ceases. We did not observe an increased risk with EPT, and with increasing time after stopping, a reduction in risk became increasingly evident. The progestogen component of HT may confer a risk reduction that is masked by an opposing effect of estrogen until, among former users, estrogenic influences have diminished. These findings, if replicated, may have implications both for public health and development of chemoprevention strategies. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2548–56)
Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus
Authors: Risques Rosa Ana , Vaughan Thomas L. , Li Xiaohong , Odze Robert D. , Blount Patricia L. , Ayub Kamran , Gallaher Jasmine L. , Reid Brian J. , Rabinovitch Peter S.
Published: December 2007

Purpose: Leukocyte telomere length has gained attention as a marker of oxidative damage and age-related diseases, including cancer. We hypothesize that leukocyte telomere length might be able to predict future risk of cancer and examined this in a cohort of patients with Barrett's esophagus, who are at increased risk of esophageal adenocarcinoma and thus were enrolled in a long-term cancer surveillance program.

Patients and Methods: In this prospective study, telomere length was measured by quantitative PCR in baseline blood samples in a cohort of 300 patients with Barrett's esophagus followed for a mean of 5.8 years. Leukocyte telomere length hazard ratios (HR) for risk of esophageal adenocarcinoma were calculated using multivariate Cox models.

Results: Shorter telomeres were associated with increased esophageal adenocarcinoma risk (age-adjusted HR between top and bottom quartiles of telomere length, 3.45; 95% confidence interval, 1.35-8.78; P = 0.009). This association was still significant when individually or simultaneously adjusted for age, gender, nonsteroidal anti-inflammatory drug (NSAID) use, cigarette smoking, and waist-to-hip ratio (HR, 4.18; 95% confidence interval, 1.60-10.94; P = 0.004). The relationship between telomere length and cancer risk was particularly strong among NSAID nonusers, ever smokers, and patients with low waist-to-hip ratio.

Conclusion: Leukocyte telomere length predicts risk of esophageal adenocarcinoma in patients with Barrett's esophagus independently of smoking, obesity, and NSAID use. These results show the ability of leukocyte telomere length to predict the risk of future cancer and suggest that it might also have predictive value in other cancers arising in a setting of chronic inflammation. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2649–55)
Vitamin D ReceptorGene Polymorphisms and Epithelial Ovarian Cancer Risk
Authors: Lurie Galina , Wilkens Lynne R. , Thompson Pamela J. , McDuffie Katharine E. , Carney Michael E. , Terada Keith Y. , Goodman Marc T.
Published: December 2007

Epidemiologic and laboratory studies support a role for the vitamin D endocrine system in ovarian carcinogenesis. The association of ovarian cancer risk with polymorphisms in the vitamin D receptor (VDR) gene, including rs10735810 (FokI), rs11568820 (Cdx-2), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI), and BsmI-ApaI-TaqI combined genotypes, was examined among 313 women with epithelial ovarian carcinoma and 574 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. The associations of VDR polymorphisms with risk were generally inconsistent across ethnic groups. Among Caucasian women (72 cases, 148 controls), heterozygous and homozygous ApaI A allele carriers were at increased ovarian carcinoma risk compared with homozygous carriers of the ApaI a allele (OR 2.8, 95% CI 1.2-7.0 and OR 3.4, 95% CI 1.3-9.1; Ptrend = 0.02). Caucasian heterozygous carriers of FokI f allele were also at increased risk of ovarian carcinoma compared with homozygous carriers of the common allele (OR 2.5, 95% CI 1.3-4.8; Ptrend = 0.04). Among Japanese women (94 cases, 173 controls), ovarian cancer risk was significantly decreased (OR 0.5, 95% CI 0.3-0.9) among Cdx-2 A allele heterozygotes compared with homozygote G allele carriers (Ptrend = 0.03). Compared with the bbaaTT BsmI-ApaI-TaqI genotype, bbaATT and BBAAtt genotypes were associated with increased ovarian cancer risk in Caucasian women (OR 4.2, 95% CI 1.3-13.1 and OR 5.2, 95% CI 1.6-17.5), but not in Japanese women (OR 1.1, 95% CI 0.6-1.9 and OR 2.3, 95% CI:0.4-12.3). This investigation provides some evidence that polymorphisms in the VDR gene might influence ovarian cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2566–71)
CDX2 VDR Polymorphism and Colorectal Cancer
Authors: Slattery Martha L. , Herrick Jennifer , Wolff Roger K. , Caan Bette J. , Potter John D. , Sweeney Carol
Published: December 2007

Studies suggest that polymorphisms of the vitamin D receptor (VDR) gene may influence colorectal cancer risk. In this study, we examine the association of the CDX2 VDR polymorphism (rs11568820) located in the 5′-untranslated region of the gene, and VDR haplotypes, including this polymorphism, with colon and rectal cancer using data from two large case-control studies of colon (N = 1,574 cases and 1,970 controls) and rectal (n = 791 cases and 999 controls) cancer. The frequency of the A allele of the CDX2 polymorphism was 19% among non–Hispanic white, 21% among Hispanic, 76% among African American, and 47% among Asian controls. The CDX2 polymorphism was not independently associated with either colon or rectal cancer, nor did it modify associations of dietary calcium, vitamin D, or fat with colon or rectal cancer. However, the bLFA haplotype which occurred in 6.5% of non–Hispanic white participants and 41.2% of African American participants was associated with an increased risk of colon cancer, and an odds ratio of 2.4 [95% confidence intervals (CI), 2.45 (1.38-4.38)]. The BSfG haplotype was associated with a 1.61 (95% CI, 1.05-2.49) increased risk of rectal but not colon cancer, whereas the BSFA haplotype was associated with a significantly reduced risk of rectal (odds ratio, 0.71; 95% CI, 0.52-0.97) but not colon cancer. These data suggest that haplotype analysis that encompasses different domains of the VDR gene might further our understanding of associations between the VDR gene and colon and rectal cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2752–5)
Predictive Coding and the Slowness Principle: An Information-Theoretic Approach
Authors: Creutzig Felix , Sprekeler Henning
Published: December 2007

Understanding the guiding principles of sensory coding strategies is a main goal in computational neuroscience. Among others, the principles of predictive coding and slowness appear to capture aspects of sensory processing. Predictive coding postulates that sensory systems are adapted to the structure of their input signals such that information about future inputs is encoded. Slow feature analysis (SFA) is a method for extracting slowly varying components from quickly varying input signals, thereby learning temporally invariant features. Here, we use the information bottleneck method to state an information-theoretic objective function for temporally local predictive coding. We then show that the linear case of SFA can be interpreted as a variant of predictive coding that maximizes the mutual information between the current output of the system and the input signal in the next time step. This demonstrates that the slowness principle and predictive coding are intimately related.
Dynamical Constraints on Using Precise Spike Timing to Compute in Recurrent Cortical Networks
Authors: Banerjee Arunava , Seriès Peggy , Pouget Alexandre
Published: December 2007

Several recent models have proposed the use of precise timing of spikes for cortical computation. Such models rely on growing experimental evidence that neurons in the thalamus as well as many primary sensory cortical areas respond to stimuli with remarkable temporal precision. Models of computation based on spike timing, where the output of the network is a function not only of the input but also of an independently initializable internal state of the network, must, however, satisfy a critical constraint: the dynamics of the network should not be sensitive to initial conditions. We have previously developed an abstract dynamical system for networks of spiking neurons that has allowed us to identify the criterion for the stationary dynamics of a network to be sensitive to initial conditions. Guided by this criterion, we analyzed the dynamics of several recurrent cortical architectures, including one from the orientation selectivity literature. Based on the results, we conclude that under conditions of sustained, Poisson-like, weakly correlated, low to moderate levels of internal activity as found in the cortex, it is unlikely that recurrent cortical networks can robustly generate precise spike trajectories, that is, spatiotemporal patterns of spikes precise to the millisecond timescale.
Almost Periodic Dynamics of a Class of Delayed Neural Networks with Discontinuous Activations
Authors: Lu Wenlian , Chen Tianping
Published: December 2007

We use the concept of the Filippov solution to study the dynamics of a class of delayed dynamical systems with discontinuous right-hand side, which contains the widely studied delayed neural network models with almost periodic self-inhibitions, interconnection weights, and external inputs. We prove that diagonal-dominant conditions can guarantee the existence and uniqueness of an almost periodic solution, as well as its global exponential stability. As special cases, we derive a series of results on the dynamics of delayed dynamical systems with discontinuous activations and periodic coefficients or constant coefficients, respectively. From the proof of the existence and uniqueness of the solution, we prove that the solution of a delayed dynamical system with high-slope activations approximates to the Filippov solution of the dynamical system with discontinuous activations.
Constrained Subspace ICA Based on Mutual Information Optimization Directly
Authors: Van Hulle Marc M.
Published: December 2007

We introduce a new approach to constrained independent component analysis (ICA) by formulating the original, unconstrained ICA problem as well as the constraints in mutual information terms directly. As an estimate of mutual information, a robust version of the Edgeworth expansion is used, on which gradient descent is performed. As an application, we consider the extraction of both the mother and the fetal antepartum electrocardiograms (ECG) from multielectrode cutaneous recordings on the mother's thorax and abdomen.