bluuebunny/crossref_metadata_2025 huggingface dataset:
Mononuclear cell infiltration in clear‐cell renal cell carcinoma independently predicts patient survival
Authors: Webster W. Scott , Lohse Christine M. , Thompson R. Houston , Dong Haidong , Frigola Xavier , Dicks Demetrius L. , Sengupta Shomik , Frank Igor , Leibovich Bradley C. , Blute Michael L. , Cheville John C. , Kwon Eugene D.
Published: May 2006

BACKGROUND

The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin‐embedded specimens with survival in patients with clear‐cell RCC.

METHODS

A total of 306 patients were identified treated with nephrectomy for clear‐cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer‐specific survival was estimated using the Kaplan–Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models.

RESULTS

At last follow‐up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P<.001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028).

CONCLUSIONS

Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC. Cancer 2006. © 2006 American Cancer Society.
Impact of fellowship training on pathologic outcomes and complication rates of radical prostatectomy
Authors: Rosser Charles J. , Kamat Ashish M. , Pendleton John , Robinson Tracy L. , Pisters Louis L. , Swanson David A. , Babaian Richard J.
Published: May 2006

BACKGROUND

The study was conducted to assess the results of radical prostatectomy (RP) performed by fellowship‐trained surgeons in the first year of independent practice.

METHODS

A prospective cohort study of 66 men who underwent RP performed by 2 recently graduated fellowship‐trained surgeons (C.J.R., n = 27; A.M.K., n = 39) in their first year of independent practice was undertaken. Preoperative, operative, and postoperative data were collected and analyzed. Median follow‐up of the cohort is 12.5 months.

RESULTS

The median patient age was 61.2 ± 6.9 years (range, 44–74 years), the median prostate‐specific antigen level was 5 ng/mL (range, 1.2–39.4 ng/mL), and the median prostate biopsy‐determined Gleason score was 7. Of the 66 men, 25 (38%) underwent a bilateral nerve‐sparing RP, 20 (30%) underwent a unilateral nerve‐sparing RP, and 21 (32%) underwent a nonnerve‐sparing procedure. Forty‐two men (63%) underwent a pelvic lymph node dissection. The median operative time was 201 minutes. Median estimated blood loss was 734 mL (range, 300–1600 mL). There were 4 major complications—a pulmonary embolism in 3 patients and an intraoperative rectal injury in 1. Pathologic classification was as follows: pT2, 74%; pT3a, 23%; pT3b, 2%; and pN+, 2%. The positive margin rate was 14% overall and only 2% in men with pT2 disease.

CONCLUSIONS

Results of RP performed by fellowship‐trained surgeons in their first year of practice compare favorably with results of RP in a large series reported by more experienced surgeons. Being trained in an environment where an experienced surgeon serves as first assistant to the trainee appears to abbreviate the learning curve associated with this procedure. Cancer 2006. © 2006 American Cancer Society.
Surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry serum protein profiling to identify nasopharyngeal carcinoma
Authors: Wing Yuen Ho David , Fan Yang Zhen , Yee‐Hang Wong Birgitta , Lai‐Wan Kwong Dora , Shun‐Tong Sham Jonathan , Ignace Wei William , Po Wing Yuen Anthony
Published: May 2006

BACKGROUND

Diagnosis of nasopharyngeal carcinoma (NPC) at an early disease stage is important for successful treatment and improving the outcome of patients. The use of serum protein profiles and a classification tree algorithm were explored to distinguish NPC from noncancer.

METHODS

Serum samples were applied to metal affinity protein chips to generate mass spectra by surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS). Protein peak identification and clustering were performed using the Biomarker Wizard software. Proteomic spectra of serum samples from 50 NPC patients and 54 noncancer controls were used as a training set and a classification tree with 6 distinct protein masses was generated by using Biomarker Pattern software. The validity of the classification tree was then challenged with a blind test set including another 20 NPC patients and 25 noncancer controls.

RESULTS

The software identified an average of 93 mass peaks/spectrum and 6 of the identified peaks were used to construct the classification tree. The classification tree correctly determined 83% (123 of 149) of the test samples with 83% (58 of 70) of the NPC samples and 82% (65 of 79) of the noncancer samples. In a combination of the serum protein profiles with Epstein–Barr (EBV) nuclear antigen 1 (EBNA1 IgA) test, the diagnostic sensitivity and specificity were increased to 99% and 96%, respectively.

CONCLUSIONS

The results suggest that SELDI‐TOF‐MS serum protein profiles could discriminate NPC from noncancer. The combination of serum protein profiles with an EBV antibody serology test could further improve the accuracy of NPC screening. Cancer 2006. © 2006 American Cancer Society.
The model for end‐stage liver disease‐based Japan Integrated Scoring system may have a better predictive ability for patients with hepatocellular carcinoma undergoing locoregional therapy
Authors: Huo Teh‐Ia , Lin Han‐Chieh , Huang Yi‐Hsiang , Wu Jaw‐Ching , Chiang Jen‐Huei , Lee Pui‐Ching , Lee Shou‐Dong
Published: May 2006

BACKGROUND

The Japan Integrated Scoring (JIS) system was revealed as a better model for outcome prediction compared with the Cancer of Liver Italian Program system for hepatocellular carcinoma (HCC), and the Model for End‐Stage Liver Disease (MELD) was better as a prognostic predictor for patients with cirrhosis compared with the Child–Turcotte–Pugh (CTP) system, which is a parameter used in the JIS system. The objective of the current study was to investigate the performance of the modified MELD‐based JIS system.

METHODS

In the modified JIS system, the CTP class in the original JIS was replaced with MELD cut‐off scores of <10, 10 to 14, and >14. The modified JIS system was compared with the original system in 276 patients with HCC who underwent locoregional therapy (transarterial chemoembolization or percutaneous injection).

RESULTS

The mean ± standard error original JIS score was 1.8 ± 1.0 (range, 0‐4), compared with 2.0 ± 1.1 (range, 0‐5) for the modified JIS system (P<.001). Using mortality as the endpoint, the area under receiver operating characteristic curve (AUC) for the modified JIS system was 0.804 compared with 0.741 for the original JIS system (P = .008) at 12 months, and the AUC was 0.853 and 0.765, respectively (P<.001), at 24 months. Survival analysis showed that the modified JIS system had a better discriminatory ability for patients in different score groups and was more accurate for outcome prediction in the Cox multivariate model.

CONCLUSIONS

The current results indicated that the MELD‐based, modified JIS system has improved predictive ability compared with the original system and is a more feasible model for clinical staging in patients with HCC who are undergoing locoregional therapy. Cancer 2006. © 2006 American Cancer Society.
On the finite‐time singularities of the 3D incompressible Euler equations
Authors: Chae Dongho
Published: May 2006

We prove the finite‐time vorticity blowup, in the pointwise sense, for solutions of the 3D incompressible Euler equations assuming some conditions on the initial data and its corresponding solutions near initial time. These conditions are represented by the relation between the deformation tensor and the Hessian of pressure, both coupled with the vorticity directions associated with the initial data and solutions near initial time. We also study the possibility of the enstrophy blowup for the 3D Euler and the 3D Navier‐Stokes equations, and prove the finite‐time enstrophy blowup for initial data satisfying suitable conditions. Finally, we obtain a new blowup criterion that controls the blowup by a quantity containing the Hessian of the pressure. © 2006 Wiley Periodicals, Inc.
On the number of interior peak solutions for a singularly perturbed Neumann problem
Authors: Lin Fang‐Hua , Ni Wei‐Ming , Wei Jun‐Cheng
Published: May 2006

We consider the following singularly perturbed Neumann problem:

where Δ = Σ ∂2/∂x is the Laplace operator, ϵ > 0 is a constant, Ω is a bounded, smooth domain in ℝN with its unit outward normal ν, and f is superlinear and subcritical. A typical f is f(u) = up where 1 < p < +∞ when N = 2 and 1 < p < (N + 2)/(N − 2) when N ≥ 3.

We show that there exists an ϵ0 > 0 such that for 0 < ϵ < ϵ0 and for each integer K bounded by

where αN, Ω, f is a constant depending on N, Ω, and f only, there exists a solution with K interior peaks. (An explicit formula for αN, Ω, f is also given.) As a consequence, we obtain that for ϵ sufficiently small, there exists at least [αN, Ωf/ϵN (|ln ϵ|)N] number of solutions. Moreover, for each m ∈ (0, N) there exist solutions with energies in the order of ϵN−m. © 2006 Wiley Periodicals, Inc.
Tg(Afp‐GFP) expression marks primitive and definitive endoderm lineages during mouse development
Authors: Kwon Gloria S. , Fraser Stuart T. , Eakin Guy S. , Mangano Michael , Isern Joan , Sahr Kenneth E. , Hadjantonakis Anna‐Katerina , Baron Margaret H.
Published: May 2006

Alpha‐fetoprotein (Afp) is the most abundant serum protein in the developing embryo. It is secreted by the visceral endoderm, its derivative yolk sac endoderm, fetal liver hepatocytes, and the developing gut epithelium. The abundance of this protein suggested that Afp gene regulatory elements might serve to effectively drive reporter gene expression in developing endodermal tissues. To this end, we generated transgenic mouse lines Tg(Afp‐GFP) using an Afp promoter/enhancer to drive expression of green fluorescent protein (GFP). Bright GFP fluorescence allowed the visualization, in real time, of visceral endoderm, yolk sac endoderm, fetal liver hepatocytes, and the epithelium of the gut and pancreas. Comparison of the localization of green fluorescence with that of endogenous Afp transcripts and protein indicated that the regulatory elements used to generate these mouse lines directed transgene expression in what appeared to be all Afp‐expressing cells of the embryo, but only in a subset of fetal liver cells. The bright GFP signal permitted flow cytometric analysis of fetal liver hepatocytes. These mice represent a valuable resource for live imaging as well as identification, quantitation, and isolation of cells from the primitive and definitive endoderm lineages of the developing mouse embryo. Developmental Dynamics 235:2549–2558, 2006. © 2006 Wiley‐Liss, Inc.
Nas transgenic mouse line allows visualization of Notch pathway activity in vivo
Authors: Souilhol Céline , Cormier Sarah , Monet Marie , Vandormael‐Pournin Sandrine , Joutel Anne , Babinet Charles , Cohen‐Tannoudji Michel
Published: May 2006

The Notch signaling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular, the precise mapping of its sites of activity, remain unclear. To address this issue, we generated a transgenic line carrying a construct consisting of a nls‐lacZ reporter gene under the control of a minimal promoter and multiple RBP‐Jκ binding sites. Here we show that this transgenic line, which we termed NAS (for Notch Activity Sensor), displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP‐Jκ‐deficient background, indicating that it indeed requires Notch/RBP‐Jκ signaling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signaling pathway. genesis 44: 277–286, 2006. © 2006 Wiley‐Liss, Inc.
Titanium–Alkaline Earth Molecular Oxides as Supports for Carbanions Derived from μ3‐Ethylidyne Groups (Eur. J. Inorg. Chem. 11/2006)
Authors: Martín Avelino , Mena Miguel , Morales‐Varela María del Carmen , Santamaría Cristina
Published: May 2006

The cover picture shows how the treatment of the oxide molecular model [{TiCp*(μ‐O)}3(μ3‐CMe)] (Cp* = η5‐C5Me5) with alkaline earth metal amide and alkyl compounds produces the deprotonation of the μ3‐ethylidyne fragment to give μ3‐CCH2−, μ3‐CHCH− or μ3‐CCH2− carbanions. Simultaneously, the alkaline earth cation is incorporated through the oxygen atoms to build new cage structures. Details of this chemistry are described by M. Mena et al. on p. 2137 ff.
Regio‐ and Stereoselective Synthesis of anti‐1,3‐Diaryl‐3‐chloro‐ 2‐(o‐nitrophenylsulfonylamino)‐3‐propan‐1‐ones through Catalytic Aminohalogenation Reaction of α,β‐Unsaturated Ketones
Authors: Liu Junying , Wang Yining , Li Guigen
Published: May 2006

The synthesis of anti‐1,3‐diaryl‐3‐chloro‐2‐(2‐nitrophenylsulfonylamino)‐3‐propan‐1‐ones has been achieved. The aminohalogenation of α,β‐unsaturated ketones resulted in the vicinal haloamine products in high regio‐ and stereoselectivity and modest to good chemical yields. The reaction can be conducted under convenient conditions by using the combination of 2‐NsNCl2/2‐NsNHNa (2‐Ns = 2‐nosyl = 2‐nitrophenylsulfonyl) as the nitrogen/chlorine source and by using copper(I) triflate as the catalyst. An N‐(2‐nosyl)‐N‐H‐aziridinium intermediate was proposed to exist in the aminohalogenation process. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
The Synthesis of 4‐Hydroxypipecolic Acids by Stereoselective Cycloaddition of Configurationally Stable Nitrones
Authors: Cordero Franca M. , Bonollo Simona , Machetti Fabrizio , Brandi Alberto
Published: May 2006

The diastereoselective synthesis of trans‐ and cis‐4‐hydroxypipecolic acids has been achieved with geometry‐controlled nitrone cycloaddition chemistry. The cycloaddition of 3‐butenol to enantiopure C‐aminocarbonyl and C‐alkoxycarbonyl nitrones having a definite (Z) and (E) configuration, respectively, occurs with complete regio‐ and exo selectivity. The acyclic (Z)‐nitrone 12 affords two cycloadducts in a 1:1 ratio, which can be separated and converted into (2R,4R)‐ and (2S,4S)‐4‐hydroxypipecolic acids, respectively, in four steps. The cyclic (E)‐nitrone 17 reacts with complete diastereofacial selectivity and the elaboration of its sole adduct gives the methyl ester of (2R,4S)‐4‐hydroxypipecolic acid, albeit in low yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A Bayesian semiparametric model for organism based environmental reconstruction
Authors: Bhattacharya Sourabh
Published: May 2006

Reconstruction of past environment based on fossil data is an important scientific problem and much work has been done to address this. One important issue in this regard is the relationship between species and environment. The available statistical approaches, both classical and Bayesian, make the assumption that species abundances occur symmetrically around a single preferable environmental condition. In other words, it is generally assumed that the relationship between species and environment is unimodal. However, this may not be true in reality.

In this paper, we propose a Bayesian hierarchical model, extending previous work, to incorporate multiple preferences (or, multiple modes) of each species. In particular, we propose to use a mixture of Gaussian response curves to relate species to environment. A main novelty of our approach is the use of Dirichlet process to learn about the number of preferences of each species. We demonstrate that our multimodal modeling approach performs better than unimodal model. For implementation of our approach, we use a recently developed efficient computational procedure. Copyright © 2006 John Wiley & Sons, Ltd.
Trees as riparian engineers: the Tagliamento river, Italy
Authors: Gurnell Angela , Petts Geoffrey
Published: May 2006

Pristine river corridors were characterized by island and floodplain development driven by the inter‐play of flows, sediments and woody vegetation. Here we explore these relationships within topographically controlled settings within the upper, middle and lower reaches of a large, semi‐natural alpine to mediterranean river. These reaches have expanding or contracting valley floors within which we show that there are more or less predictable patterns of stream power and rates of vegetation growth, reflecting water availability during dry periods and also the availability of sand and finer sediment. We relate these to the pattern of island distribution that is repeated within the three reaches and is indicative of the engineering role of riparian trees. Islands are shown to develop within thresholds defined by stream power, rates of woody vegetation growth and rates of sedimentation, and to develop most quickly where riparian species include those capable of sprouting from driftwood. Copyright © 2006 John Wiley & Sons, Ltd.
Multi‐year tracking of sediment sources in a small agricultural watershed using rare earth elements
Authors: Kimoto A. , Nearing M. A. , Shipitalo M. J. , Polyakov V. O.
Published: May 2006

Rare earth elements (REEs) have been successfully used as a sediment tracer, but the REE technique has never been used for studying sediment sources for a multi‐year period. A nearly four‐year field experiment was conducted on a small agricultural watershed near Coshocton, OH, USA, to assess the applicability of the REE technique for a multi‐year period and to evaluate the relative contributions of sediment sources in the watershed. Tracer depletion and tracer enrichment ratio (ratio of the tracer concentrations in sediment to the concentrations in the soil in the areas of application) were evaluated to examine the applicability and accuracy of the technique. A minimum of 91 per cent of the mass of the applied elements was still available on any individual morphological element at the end of the experimental period. The tracer enrichment ratio varied from 0·4 to 2·3, and it was not significantly related to time. The relative contributions of six morphological elements within the watershed were evaluated as proportions to total sediment yield. The relative contribution of the lower channel was significantly increased as a function of the amount of sediment yield, while that of the lower backslope was significantly decreased. The relative contribution of the lower channel significantly decreased as a function of cumulative sediment yield, while the contributions of the shoulder and the upper backslope significantly increased. Our results showed that the REE technique can be used to track sediment sources for a relatively long period with two limitations or potential sources of error associated with a selective depletion of tracers and a contamination of downslope areas with tagged sediments from upslope areas. Copyright © 2006 John Wiley & Sons, Ltd.
Lithological control on the elevation of shore platforms in a microtidal setting
Authors: Kennedy D. M. , Dickson M. E.
Published: May 2006

The shore platforms on Shag Point, southern New Zealand, are quasi‐horizontal surfaces and are developed between supratidal and low water spring levels. A range of morphologies occur, with more exposed platforms having a distinct low‐tide cliff, in contrast to low‐tide surfaces where the seaward edge is buried beneath rubble and macro‐algal growth. The platforms range in width from 20 to 80 m and are eroded into Late Cretaceous/Early Tertiary fine marine sandstones and mudstones. Shore platforms have formed in two principal lithological units: a homogeneous unit that is characterized by few discontinuities, and a fractured unit with joints spaced about 0·5 m apart. Rock hardness is low in both units (L‐type Schmidt hammer rebound values of 31 ± 4), and there is little systematic variation in values between the two units in which platforms have developed. Case‐hardened concretions within the sandstone are significantly harder than surrounding rock and cause local relief of metre scale as the spherical diagenetic features are eroded from the bedrock. They do not, however, appear to affect broad‐scale platform geometry. Joints within the bedrock are a primary control on platform elevation. Platforms formed in jointed rock occur at the lower portion of the intertidal zone, in contrast to platforms formed in unjointed bedrock, in which horizontal surfaces occur at or above mean high water spring tide level. Rock structure, therefore, appears to be the primary determinant factor of platform geometry at Shag Point. Copyright © 2006 John Wiley & Sons, Ltd.
Bank stability analysis for regime models of vegetated gravel bed rivers
Authors: Eaton Brett C.
Published: May 2006

A new bank stability analysis procedure is developed for use in rational regime models predicting reach average channel dimensions. The performance of a regime model using this new bank stability formulation is compared against that for a model using the modified friction angle approach proposed by Millar and Quick (1993). The bank stability assessment is based on a conceptual model that more closely represents conditions found in gravel bed rivers with vegetated floodplains: the primary effect of vegetation is its contribution to a stable upper bank, the position of which is determined by erosion of unvegetated bed material at the toe of the bank. The vertical height of the upper bank is estimated using a simple slab failure model and assigning an effective cohesion to the vegetation‐reinforced soil. The geometry of the lower slope and the width of the channel are determined iteratively using the regime approach described by Eaton et al. (2004). A comparison of the predicted stream channel widths for stable gravel bed channels classified according to riparian vegetation type (Hey and Thorne, 1986) showed that this new formulation increases model accuracy, especially for the more densely vegetated channel types. Since the strength parameters used in the model can be estimated from the observed bank geometry, the potential for applying and testing rational regime models in the field has been significantly improved. Copyright © 2006 John Wiley & Sons, Ltd.
Divergent response of an intertidal swash bar
Authors: Houser Chris , Greenwood Brian , Aagaard Troels
Published: May 2006

This paper examines the processes responsible for the morphodynamics of an intertidal swash bar at Skallingen, Denmark, during seven successive storms (one with a large surge of +3·02 m DNN). During this period a subtidal bar migrated landward onto the foreshore and continued to migrate across the intertidal zone as a swash bar. The onshore migration of the inner subtidal bar resulted from the erosion of sediment from the upper foreshore and dune ramp during the large storm surge that was transported seaward, causing the landward displacement of the bar through accretion on the landward slope. The magnitude and direction of suspended sediment transport within the intertidal zone, and more specifically at and close to the crest of the swash bar, varied with the ratio of both the significant (Hs) and average (Havg) wave heights to the water depth (hcr) at the swash bar crest (the local depth minimum). The transition between onshore and offshore suspended sediment transport was associated with the average wave of the incident distribution breaking on the swash bar crest (Havgh ≈ 0·33). While the onshore‐directed transport was largest at infragravity frequencies, sediment resuspension was best explained by the skewed accelerations under the surf bores. Offshore transport was dominated by the cross‐shore mean currents (undertow) that developed when the significant wave of the distribution broke on the swash bar crest (Hsh ≈ 0·33) and weakened as the average wave of the distribution started to break at the crest (Havgh ≈ 0·33) and the surf zone approached saturation. In contrast to subtidal bars, the swash bar at Skallingen exhibited a divergent behaviour with respect to the cross‐shore position of the breaker zone, migrating onshore when the average wave broke seaward of the crest and migrating offshore when the average wave broke landward of the crest. Copyright © 2006 John Wiley & Sons, Ltd.
Investigation of coupling between surface processes and induced flow in the lower continental crust as a cause of intraplate seismicity
Authors: Westaway Rob
Published: May 2006

Many studies have highlighted the role of coupling between surface processes and flow in the lower continental crust in deforming the crust and creating topographic relief over Quaternary timescales. On the basis of the rheological knowledge gained, it is suggested that intraplate seismicity can also be caused by coupling between surface processes and flow in the lower continental crust. This view is shown to be a natural consequence of the modern idea that isostatic equilibrium is maintained by flow in the weak lower crust in response to erosion and sedimentation. It is supported by a general correlation between the vigour of surface processes and rates of intraplate seismicity, and by instances of seasonal seismicity that correlates with seasonal climate. Human interference in the environment can affect surface loading: for instance, deforestation for agriculture or urban development can cause increased erosion rates; global warming is expected to cause increased storminess (and thus increased erosion rates) and/or global sea‐level rise. The possibility of increased rates of seismicity resulting from these processes should thus be considered in future hazard assessment. Copyright © 2006 John Wiley & Sons, Ltd.
Modelling the potential impacts of groundwater hydrology on long‐term drainage basin evolution
Authors: Huang Xiangjiang , Niemann Jeffrey D.
Published: May 2006

Fluvial erosion processes are driven by water discharge on the land surface, which is produced by surface runoff and groundwater discharge. Although groundwater is often neglected in long‐term landscape evolution problems, water table levels control patterns of Dunne runoff production, and groundwater discharge can contribute significantly to storm flows. In this analysis, we investigate the role that groundwater movement plays in long‐term drainage basin evolution by modifying a widely used landscape evolution model to include a more detailed representation of basin hydrology. Precipitation is generated by a stochastic process, and the precipitation is partitioned between surface runoff and groundwater recharge using a specified infiltration capacity. Groundwater flow is simulated by a dynamic two‐dimensional Dupuit equation for an unconfined aquifer with an irregular underlying impervious layer. The model is applied to the WE‐38 basin, an experimental catchment in Pennsylvania, because 60–80 per cent of the discharge is derived from groundwater and substantial hydrologic and geomorphic information is available. The hydrologic model is first calibrated to match the observed streamflows, and then the combined hydrologic/geomorphic model is used to simulate scenarios with different infiltration capacities. The results of this modelling exercise indicate that the basin can be divided into three zones with distinct streamflow‐generating characteristics, and different parts of the basin can have different geomorphic effective events. Over long periods of time, scenarios in which groundwater discharge is large tend to modify the topography in a way that promotes groundwater discharge and inhibits Dunne runoff. Copyright © 2006 John Wiley & Sons, Ltd.
Aeolian sediment transport on a human‐altered foredune
Authors: Nordstrom Karl F. , Jackson Nancy L. , Hartman Jean Marie , Wong Mark
Published: May 2006

Changes in wind speed and sediment transport are evaluated at a gap and adjacent crest of a 2 to 3 m high, 40 m wide foredune built by sand fences and vegetation plantings on a wide, nourished fine sand beach at Ocean City, New Jersey. Anemometer masts, cylindrical sand traps and erosion pins were placed on the beach and dune during two obliquely onshore wind events in February and March 2003. Results reveal that: (1) changes in the alongshore continuity of the beach and dune system can act as boundaries to aeolian transport when winds blow at an angle to the shoreline; (2) oblique winds blowing across poorly vegetated patches in the dune increase the potential for creating an irregular crest elevation; (3) transport rates and deflation rates can be greater within the foredune than on the beach, if the dune surface is poorly vegetated and the beach has not had time to dry following tidal inundation; (4) frozen ground does not prevent surface deflation; and (5) remnant sand fences and fresh storm wrack have great local but temporary effect on transport rates. Temporal and spatial differences due to sand fences and wrack, changes in sediment availability due to time‐dependent differences in surface moisture and frozen ground, combined with complex topography and patchy vegetation make it difficult to specify cause–effect relationships. Effects of individual roughness elements on the beach and dune on wind flow and sediment transport can be quantified at specific locations at the event scale, but extrapolation of each event to longer temporal and spatial scales remains qualitative. Copyright © 2006 John Wiley & Sons, Ltd.
k‐Version of finite element method in 2‐D polymer flows: Oldroyd‐B constitutive model
Authors: Surana K. S. , Mohammed A. , Reddy J. N. , TenPas P. W.
Published: May 2006

In this paper, a new mathematical framework based on h, p, k and variational consistency (VC) of the integral forms is utilized to develop a finite element computational process of two‐dimensional polymer flows utilizing Oldroyd‐B constitutive model. Alternate forms of the choices of dependent variables in the governing differential equations (GDEs) are considered and is concluded that u, v, p, τ choice yielding strong form of the GDEs is meritorious over others. It is shown that: (a) since, the differential operator in the GDEs is non‐linear, Galerkin method and Galerkin method with weak form are variationally inconsistent (VIC). The coefficient matrices in these processes are non‐symmetric and hence may have partial or completely complex basis and thus the resulting computational processes may be spurious. (b) Since the VC of the VIC integral forms cannot be restored through any mathematically justifiable means, the computational processes in these approaches always have possibility of spurious solutions. (c) Least squares process utilizing GDEs in u, v, p, τ (strong form of the GDEs) variables (as well as others) is variationally consistent. The coefficient matrices are always symmetric and positive definite and hence always have a real basis and thus naturally yield computational processes that are free of spurious solutions. (d) The theoretical solution of the GDEs are generally of higher order global differentiability. Numerical simulations of such solutions in which higher order global differentiability characteristics of the theoretical solution are preserved, undoubtedly requires local approximations in higher order scalar product spaces ${H}^{k,p}(\bar{\Omega}_{e})$. (e) LSP with local approximations in ${H}^{k,p}(\bar{\Omega}_{e})$ spaces provide an incomparable mathematical and computational framework in which it is possible to preserve desired characteristics of the theoretical solution in the computational process. Numerical studies are presented for fully developed flow between parallel plates and a lid driven square cavity. M1 fluid is used in all numerical studies. The range of applicability of the Oldroyd‐B model or lack of it is examined for both model problems for increasing De. A mathematical idealization of the corners where stationary wall meets the lid is presented and is shown to simulate the real physics when the local approximations are in higher order spaces and when hd→0. For both model problems shear rate $\hat{\dot{\gamma}}$ is examined in the flow domain to establish validity of the Oldroyd‐B constitutive model. Copyright © 2006 John Wiley & Sons, Ltd.
Mutational dynamics in human tumors confirm the neutral intrinsic instability of the mitochondrial D‐loop poly‐cytidine repeat
Authors: Schwartz Simó , Alazzouzi Hafid , Perucho Manuel
Published: May 2006

Somatic mutations at a mitochondrial noncoding polycytidine (C)n repeat (polyC) have been associated with tumor progression. We analyzed whether these alterations are due to the inherent mutability of repeated sequences. Insertion and deletion mutations were found in colon (n = 114), stomach (n = 105), endometrium (n = 53), breast (n = 45), lung (n = 35), and prostate (n = 20) tumors. The mutation frequency in colon, gastric, and endometrial tumors was 23, 17, and 11%, respectively, which paralleled the relative extent of microsatellite instability in long mononucleotide repeats observed in tumors with mismatch repair deficiency (colon > stomach > endometrium, relative ratio 10:8:4). Colon tumors with mutations of more than one nucleotide were more advanced in tumor progression. Further, two tumors showing a T > C mutation that restored the homopolymeric repeat, harbored sequential deletion mutations of up to 4 and 6 nucleotides. These results illustrate that the increased mutability of repeated mitochondrial sequences is dependent on the repetitive structure of the DNA molecule and suggest that mutations in the (C)n repeat, whether homoplasmic or not, and by extrapolation, mitochondrial mutations in general, are not the result of selective pressure during tumorigenesis. We also suggest that the (C)n repeat may be used as an universal molecular clock to estimate the relative mitotic history of tumors. © 2006 Wiley‐Liss, Inc.
Prognostic significance of cyclin A in gastric cancer
Authors: Mrena Johanna , Wiksten Jan‐Patrik , Kokkola Arto , Nordling Stig , Haglund Caj , Ristimäki Ari
Published: May 2006

High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in ≥≥≥≥5% of the tumor cells was considered the cut‐off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the χ2‐test, Fisher's exact test, Kaplan‐Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR. © 2006 Wiley‐Liss, Inc.
Prevalence and determinants of human papillomavirus infection in men attending vasectomy clinics in Mexico
Authors: Vaccarella Salvatore , Lazcano‐Ponce Eduardo , Castro‐Garduño José Antonio , Cruz‐Valdez Aurelio , Díaz Vicente , Schiavon Rafaela , Hernández Pilar , Kornegay Janet R. , Hernández‐Avila Mauricio , Franceschi Silvia
Published: May 2006

Large studies of genital human papillomavirus (HPV) infection in men are few and mainly include high‐risk groups. We interviewed 779 men who requested a vasectomy in 27 public clinics in 14 states of Mexico. Exfoliated cells were obtained from the scrotum, the shaft of the penis, the top of the penis including the coronal sulcus, the glans and the opening of the meatus. HPV testing was performed using biotinylated L1 consensus primers and reverse line blot. Unconditional logistic regression was used to estimate odds ratios (ORs) of being HPV‐positive and corresponding 95% confidence intervals (CIs). The prevalence of any type of HPV was 8.7%. HPV positivity was highest among men below age 25 (13.6%), and lowest among men aged 40 years or older (6.0%). The most commonly found HPV types were, in decreasing order, HPV59, 51, 6, 16 and 58. Lifetime number of sexual partners was associated with HPV positivity (OR for ≥4 vs. 1 partner = 3.7, 95% CI: 2.0–6.8), mainly on account of the strong association with number of occasional and sex‐worker partners. Condom use with both regular (OR = 0.4, 95% CI: 0.1–1.0) and sex‐worker (OR = 0.1, 95% CI: 0.0–0.3) partners and circumcision (OR = 0.2, 95% CI: 0.1–0.4) were inversely associated with HPV positivity. HPV prevalence in Mexican men was similar to the prevalence found in Mexican women of the same age groups. The association between HPV positivity and lifetime number of sexual partners in the present low‐risk male population is one of the strongest ever reported in studies in men. Condom use and circumcision were associated with a strong reduction in HPV prevalence. © 2006 Wiley‐Liss, Inc.
A highly specific real‐time RT‐PCR method for the quantitative determination of CK‐19 mRNA positive cells in peripheral blood of patients with operable breast cancer
Authors: Stathopoulou Aliki , Ntoulia Maria , Perraki Maria , Apostolaki Stella , Mavroudis Dimitris , Malamos Nikos , Georgoulias Vassilis , Lianidou Evi S.
Published: May 2006

The aim of the present study was to decrease the incidence of false positives and to better characterize marginally cytokeratin‐19 (CK‐19) mRNA positive peripheral blood samples from patients with early stage breast cancer. A new set of highly specific primers for CK‐19, which avoids amplification of contaminating genomic DNA, was designed and evaluated to improve the specificity and sensitivity of the previously described methodology. The primers were specifically designed to avoid amplification of contaminating genomic DNA and CK‐19 pseudogenes. The breast cancer cell line MCF‐7 was used as positive control for the development and analytical evaluation of the assay, while peripheral blood samples from 62 healthy female individuals and 160 patients with early breast cancer were used for the evaluation of the sensitivity and specificity of the new primer pair. The novel designed primer pair was highly sensitive, as it detects up to 1 MCF‐7 cell, and specific as none of the healthy individuals had detectable CK‐19 mRNA positive cells in their peripheral blood. CK‐19 mRNA positive cells were detected in 33 out of 160 (20.6%) patients with early breast cancer. Results obtained by the proposed optimized real‐time RT‐PCR protocol correlated well with those obtained in the same samples by our previously reported quantitative real‐time RT‐PCR [concordance in 198/222 (89.2%), p = 0.0022, McNemar test]. The improved method eliminates the incidence of false positives and is highly sensitive and specific. The method could be used in a clinical setting in the near future for continuous monitoring and quantification of circulating epithelial cells in the peripheral blood of patients with operable breast cancer, provided that a quite larger number of clinical samples with a known follow‐up will be analyzed. © 2006 Wiley‐Liss, Inc.
Food patterns and risk of breast cancer: A factor analysis study in Uruguay
Authors: Ronco Alvaro L. , De Stefani Eduardo , Boffetta Paolo , Deneo‐Pellegrini Hugo , Acosta Giselle , Mendilaharsu María
Published: May 2006

To generate broad eating patterns, which could explain more adequately the breast cancer etiology, we conducted an exploratory factor analysis in Montevideo, Uruguay. The study included 442 newly diagnosed and microscopically confirmed cases with breast cancer and 442 hospitalized controls, with non‐neoplastic diseases. Factor analysis (principal components) was conducted in the control series, and as a result, 6 factors were extracted. These factors were labeled as traditional, healthy, western, stew, high‐fat and drinker. The model explained 58.3% of the variance. After scoring the rotated factors, the relations between scores and breast cancer risk factors were analyzed by using Pearson correlation coefficients. After this step, the odds ratios of breast cancer for continuous scores of the rotated factors were carefully analyzed. The highest risk was directly associated with the western diet (OR 1.31, 95% CI 1.13–1.51), whereas the traditional (OR 0.77, 95% CI 0.64–0.93), healthy (OR 0.84, 95% CI 0.73–0.98) and stew (OR 0.83, 95% CI 0.71–0.98) diets were significantly protective. Women who reported a history of breast cancer among mother and sisters displayed strong elevations in risk for western (OR 2.03, 95% CI 1.11–3.72) and high‐fat (OR 2.72, 95%CI 1.16–6.37) dietary patterns. This finding could suggest that gene–dietary interaction could play an important role in breast carcinogenesis. © 2006 Wiley‐Liss, Inc.
Adenovirus‐mediated tBid overexpression results in therapeutic effects on p53‐resistant hepatocellular carcinoma
Authors: Miao Ji , Chen George G. , Chun Suk‐Ying , Yun Jing‐Ping , Chak Ernest C.W. , Ho Rocky L.K. , Lai Paul B.S.
Published: May 2006

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with a very high mortality. Because the success of the conventional therapies is limited, gene therapy may represent an alternative for HCC management. Our earlier study has shown that Bid plays a role in the development of HCC. The aim of our study is to evaluate the possibility of using truncated Bid (tBid) as a novel therapy for HCC treatment. Two HCC cell lines, Hep3B and PLC/PRF/5, were used in the experiment. Hep3B was a p53‐resistant while PLC/PRF/5 a p53‐sensitive. A recombinant adenovirus‐Ad/AFPtBid, which contained a tBid gene driven by an α‐fetoprotein (AFP) promoter, was constructed. Both Hep3B and PLC/PRF/5 cells infected with Ad/AFPtBid showed a significant decrease in cell viability. The decrease in cell viability by Ad/AFPtBid resulted from apoptosis of HCC cells, evident by enhanced activity of caspases and increased release of cytochrome c. In vivo experiment was performed by the intratumor injection of Ad/AFPtBid in nude mice inoculated with Hep3B. Ad/AFPtBid injection significantly inhibited tumor growth, and tumor tissues showed a marked increase in TUNEL‐positive cells. Our experiment also demonstrated that Ad/AFPtBid only targeted AFP‐producing cells but not those non‐AFP producing cells. In conclusion, these results indicate that the introduction of Ad/AFPtBid can not only significantly but specifically kill HCC cells that produce AFP. The cell death induced by Ad/AFPtBid in HCC cells is via an apoptotic pathway that can be independent of p53 status. © 2006 Wiley‐Liss, Inc.
Secular trends and geographic variations of hepatitis B virus and hepatitis C virus‐associated hepatocellular carcinoma in Taiwan
Authors: Lu Sheng‐Nan , Su Wei‐Wen , Yang Sheng‐Shun , Chang Ting‐Tsung , Cheng Ken‐Sheng , Wu Jaw‐Ching , Lin Hans Hsienhong , Wu Shun‐Sheng , Lee Chuan‐Mo , Changchien Chi‐Sin , Chen Chien‐Jen , Sheu Jin‐Chuan , Chen Ding‐Shinn , Chen Chien‐Hung
Published: May 2006

Etiological variations in hepatocellular carcinoma (HCC) exist across different geographic areas. To gain better control of HCC, we retrospectively studied the secular trends and geographic variations in hepatitis B virus (HBV)‐related and hepatitis C virus (HCV)‐related HCCs in Taiwan. A total of 18,423 HCC cases enrolled in 8 medical centers from 1981 to 2001 were reviewed. Overall, 67% of male HCC in Taiwan was related to HBV infection whereas 55.2% of female HCC in Taiwan was related to HCV infection. The mean age of patients with HBV‐related HCC was 53.2 ± 13.6 years, while the mean age of patients with HCV‐related HCC was 65.1 ± 9.1 years (p < 0.001). The male/female ratio was 6.4 for HBV‐related HCC, while it was 1.7 for the HCV‐related HCC (p < 0.001). The percentage of HBV‐related HCC progressively decreased from 81.5 to 66.2% in males, and from 66.7 to 41.4% in females over the study period. Our study demonstrates that the percentage of HBV‐related HCC has progressively decreased over the last 20 years. The relative decrease in HBV‐related HCC was not due to a decrease in HBV‐related HCC death. Instead, it was caused by an increase in HCV‐related HCC. Prevention of new HCV infection and the treatment of chronic hepatitis C should be the primary goals, which will result in better control of HCC in the future, even in an HBV‐endemic area like Taiwan. © 2006 Wiley‐Liss, Inc.
CYP24, the enzyme that catabolizes the antiproliferative agent vitamin D, is increased in lung cancer
Authors: Parise Robert A. , Egorin Merrill J. , Kanterewicz Beatriz , Taimi Mohammed , Petkovich Martin , Lew April M. , Chuang Samuel S. , Nichols Mark , El‐Hefnawy Talal , Hershberger Pamela A.
Published: May 2006

1α,25‐Dihydroxyvitamin D3 (1,25D3) displays potent antiproliferative activity in a variety of tumor model systems and is currently under investigation in clinical trials in cancer. Studies were initiated to explore its potential in nonsmall cell lung cancer (NSCLC), as effective approaches to the treatment of that disease are needed. In evaluating factors that may affect activity in NSCLC, the authors found that CYP24 (25‐hydroxyvitamin D3‐24‐hydroxylase), the enzyme that catabolizes 1,25D3, is frequently expressed in NSCLC cell lines but not in the nontumorigenic bronchial epithelial cell line, Beas2B. CYP24 expression by RT‐PCR was also detected in 10/18 primary lung tumors but in only 1/11 normal lung tissue specimens. Tumor‐specific CYP24 upregulation was confirmed at the protein level via immunoblot analysis of patient‐matched normal lung tissue and lung tumor extracts. Enzymatically active CYP24 is expected to desensitize NSCLC cells to 1,25D3. The authors therefore implemented a high performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) assay for 1,25D3 and its CYP24‐generated metabolites to determine whether NSCLC cells express active enzyme. Analysis of NSCLC cell cultures revealed time‐dependent loss of 1,25D3 coincident with the appearance of CYP24‐generated metabolites. MK‐24(S)‐S(O)(NH)‐Ph‐1, a specific inhibitor of CYP24, slowed the loss of 1,25D3 and increased 1,25D3 half‐life. Furthermore, combination of 1,25D3 with MK‐24(S)‐S(O)(NH)‐Ph‐1 resulted in a significant decrease in the concentration of 1,25D3 required to achieve maximum growth inhibition in NSCLC cells. These data suggest that increased CYP24 expression in lung tumors restricts 1,25D3 activity and support the preclinical evaluation of CYP24 inhibitors for lung cancer treatment. © 2006 Wiley‐Liss, Inc.