bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental investigation of variable density flow and mixing in homogeneous and heterogeneous media
Authors: Schincariol Robert A. , Schwartz Franklin W.
Published: February 2008

This study is an experimental investigation of variable density groundwater flow in homogeneous, layered and lenticular porous media. At the scale of the experiments the flow of dissolved mass in water depends upon both forced and free convection. In addition, density differences as low as 0.0008 g/cm3 (1000 mg/L NaCl) between a plume of dense water and ambient groundwater in a homogeneous medium produces gravitational instabilities at realistic groundwater velocities. These instabilities are manifest by lobe‐shaped protuberances that formed first along the bottom edge of the plume and later within the plume. As the density difference increases to 0.0015 g/cm3 (2000 mg/L NaCl), 0.0037 g/cm3 (5000 mg/L NaCl), or higher, this unstable mixing due to convective dispersion significantly alters the spreading process. In a layered medium, reductions in hydraulic conductivity of the order of half an order of magnitude or less can influence the flow of the dense plume. Dense water may accumulate along bedding interfaces, which when dipping can result in plume migration velocities larger than ambient groundwater velocities. In a lenticular medium the combination of convective dispersion and nonuniform flow due to heterogeneities result in relatively large dispersion. Scale considerations, further, indicate that convective dispersion may provide an important component of mixing at the field scale.
Uncertainty propagation with numerical models for flow and transport in the unsaturated zone
Authors: Protopapas Angelos L. , Bras Rafael L.
Published: February 2008

Uncertainty propagation with numerical models for flow and transport in the unsaturated zone is studied using vector state‐space methods. The output uncertainty is the result of spatially, randomly varying parameters describing the soil hydraulic properties. An efficient state covariance propagation method is proposed, based on first‐order linearization of the system dynamics. The approach has been previously used with groundwater flow models, and this paper contributes an original generalization for unsaturated flow, including solute transport. Comparisons are made with Monte Carlo simulations of infiltration in two soils with distinctly different soil properties. For coefficients of variation of the parameters less than 0.3 the two methods agree well. The linearization method is found to be faster due to its analytical nature. The results are a promising first step for future research on parameter estimation and optimization, using the state‐space linearization approach.
The diversion capacity of capillary barriers
Authors: Ross Benjamin
Published: February 2008

An arrangement of unsaturated fine‐grained soil overlying unsaturated coarse‐grained soil along a sloping contact can, under appropriate circumstances, divert infiltrating water away from the coarser material. Such an arrangement is called a capillary barrier. The water diverted by a capillary barrier flows downdip above the contact. The volume of water moving laterally increases in the downdip direction as additional infiltration is diverted by the barrier. Sufficiently far downdip, the laterally moving water wets the contact to the point that an amount of water equal to the infiltration flows downward through the coarse soil. The lateral flow at such a point represents the diversion capacity of the capillary barrier because this flow will not increase farther downdip. If the width (measured in the direction of dip) of the system is large enough that total infiltration exceeds the diversion capacity, the downdip portion of the barrier will not be effective. The diversion capacity can be calculated exactly in the quasi‐linear approximation where the relationship between relative permeability krel and pressure potential ψ takes the form krel = eαψ. This calculation shows that an upper bound on the width of capillary barriers is Ks tan ø/qα, where Ks is the saturated hydraulic conductivity of the fine soil, ø is the dip angle of the contact, and q is the infiltration rate.
An Approximation for the Bank Storage Effect
Authors: Hunt Bruce
Published: February 2008

A perturbation procedure is used to calculate an approximate flood‐routing solution for the coupled groundwater and open channel flow equations. Seepage is initially neglected to calculate the solution of the linearized kinematic wave equations. The kinematic wave solution is then used to obtain a solution for the groundwater problem, and this groundwater solution is used to obtain a second‐order solution for the flood‐routing problem. The solution has a relatively simple form that is easily applied, and an example suggests that changes created in the downstream hydrograph by bank storage can be of the same order as changes created by retaining all terms in the open channel flow equations and routing the flood down the channel with zero bank storage.
Dissolution of Trapped Nonaqueous Phase Liquids: Mass Transfer Characteristics
Authors: Miller Cass T. , Poirier‐McNeil Michele M. , Mayer Alex S.
Published: February 2008

Many groundwater contamination incidents begin with the release of an essentially immiscible fluid into the subsurface environment. Once in the subsurface, an immiscible fluid participates in a complex pattern of transport processes. For immiscible fluids that are commonly found in contaminated groundwater environments the interphase mass transfer between the nonaqueous phase liquids (NAPLs) phase and the aqueous phase is an important process. An experimental apparatus and procedure were used to isolate and measure mass transfer between toluene and water in glass bead media systems. The rate of interphase mass transfer was investigated in two‐fluid systems as a function of aqueous phase velocity, aqueous‐ and nonaqueous‐phase fluid saturations, and porous media characteristics. The rate of interphase mass transfer is found to be directly related to aqueous phase velocity and nonaqueous phase fluid saturation level, but no significant relation to mean particle size is found. Correlation expressions for the rate of interphase mass transfer are developed using relevant dimensionless parameters and are compared to literature values. Equilibrium between the two fluid phases investigated is shown to be achieved rapidly, over wide ranges of nonaqueous phase fluid saturations and aqueous phase velocities. The derived correlations provide a means for estimating the appropriateness of the local equilibrium assumption for a nonaqueous phase liquid‐aqueous phase couple in multiphase groundwater systems.
Marginal Economic Value of Streamflow: A Case Study for the Colorado River Basin
Authors: Brown Thomas C. , Harding Benjamin L. , Payton Elizabeth A.
Published: February 2008

The marginal economic value of streamflow leaving forested areas in the Colorado River Basin was estimated by determining the impact on water use of a small change in streamflow and then applying economic value estimates to the water use changes. The effect on water use of a change in streamflow was estimated with a network flow model that simulated salinity levels and the routing of flow to consumptive uses and hydroelectric dams throughout the Basin. The results show that, under current water management institutions, the marginal value of streamflow in the Colorado River Basin is largely determined by nonconsumptive water uses, principally energy production, rather than by consumptive agricultural or municipal uses. The analysis demonstrates the importance of a systems framework in estimating the marginal value of streamflow.
Groundwater and Wetland Contributions to Stream Acidification: An Isotopic Analysis
Authors: Wels Christoph , Cornett R. Jack , LaZerte Bruce D.
Published: February 2008

Stream water pH may be influenced by (1) the flow paths and (2) the residence time of water that contributes to streamflow, when these hydrologic factors interact with the biogeochemical processes that neutralize H+ ions in the catchment. This paper presents measures of the volumes of groundwater contributing to streamflow, the groundwater residence times, and the sources of stream water acidity found during spring runoff in three basins on the Canadian Shield. Isotopic hydrograph separations were used to estimate the relative contributions of groundwater to spring runoff. The contributions of old (premelt) groundwater to spring runoff were greater (60%) in a well‐buffered, third‐order basin than in a more acidic first‐order basin (49%). Using a simple mixing model, a larger groundwater reservoir (420 mm unit depth) and longer residence time (162 days) were estimated in the third‐order basin. The lowest stream pH (4.8) was observed in a second‐order basin with a wetland that collects drainage from about 79% of the basin. In this basin the principal source of H+ ions was the conifer‐sphagnum wetland. We conclude that the hypotheses that the pH of these streams was proportional to (1) a fraction of streamflow contributed by groundwater or (2) the residence time of water in a basin are rejected. More attention must be focused upon the source of acidity generated in wetlands, since these are ubiquitous in small basins.
Long pulse large area beam extraction with a rf driven H−∕D− source
Authors: Kraus W. , Falter H.-D. , Fantz U. , Franzen P. , Heinemann B. , McNeely P. , Riedl R. , Speth E.
Published: February 2008

IPP Garching is heavily involved in the development of the rf driven H−∕D− ion source for the ITER NBI. After the successful demonstration of the required physical parameters, the experimental conditions have been extended to long pulses and large area beam extraction. This paper contains descriptions of the source and power supply modifications necessitated for long pulses as well as the latest results including the first 1h pulse. Suppression of the coextracted electron current is a key issue. Experiments with potential control, different magnetic filter fields, and cesium handling to suppress the electrons and stabilize the currents are also reported.
Photodetachment diagnostics of a volume production type negative ion source with a diode-laser
Authors: Matsuda Y. , Kasuya T. , Takahashi H. , Wada M. , Nishiura M.
Published: February 2008

Time evolution of photodetachment perturbation signal induced by a diode laser was observed in an O2 plasma. Photodetachment current collected by a Langmuir probe was directly measured and recorded by a digital oscilloscope. After integrating the recorded signal data, the waveform of the photodetachment current showed a time dependence resembling an error function. The waveform had changed its shape in accordance as the position between the probe and the laser beam axis was changed. These characteristics of the photodetachment signal are well explained by a diffusion model. The method has the possibility to yield information on various negative ion containing plasmas, but requires quiescence in the electron saturation current with the fluctuation level less than 10−4.
A breathing wormlike chain model on DNA denaturation and bubble: Effects of stacking interactions
Authors: Kim Jae-Yeol , Jeon Jae-Hyung , Sung Wokyung
Published: February 2008

DNA stably exists as a double-stranded structure due to hydrogen-bonding and stacking interactions between bases. The stacking interactions are strengthened when DNA is paired, which results in great enhancement of bending rigidity. We study the effects of this stacking-induced stiffness difference on DNA denaturation and bubble formations. To this end, we model double-stranded DNA as a duplex of two semiflexible chains whose persistence length varies depending on the base-pair distance. Using this model, we perform the Langevin dynamics simulation to examine the characteristics of the denaturation transition and the statistics of the bubbles. We find that the inclusion of the stacking interactions causes the denaturation transition to be much sharper than otherwise. At physiological temperature, the stacking interactions prohibit the initiation of bubble formation but promote bubbles, once grown, to retain the large size.
Ferromagnetic resonance in ferromagnetic/ferroelectric Fe∕BaTiO3∕SrTiO3(001)
Authors: Yu Chengtao , Pechan Michael J. , Srivastava Swedesh , Palmstrøm Chris J. , Biegaslski Michael , Brooks Charles , Schlom Darrell
Published: February 2008

Single Fe(001) films (30nm thick) have been epitaxially grown on ferroelectric BaTiO3∕SrTiO3(001) substrates at different growth temperatures to study the mutual interaction between the multiferroic components. This paper reports on the as-grown magnetic properties of the structures as a precursor to a full investigation of the multiferroic interactions. Ferromagnetic resonance measurements were carried out at 36GHz cavity and variable frequency microstrip resonators. Dual resonance modes are observed in the film, which are attributed to relaxed Fe in the film interior and strained Fe at the interface. Fourfold anisotropy is present for both modes with energy density consistent with that of bulk Fe. The interface mode is characterized by a large out-of-plane anisotropy comparable and opposite in sign to the shape anisotropy. This strained interfacial Fe should serve to couple the multiferroic components in this system. Dispersion curves show both optic and acoustic branches along the hard axis [110], with the optic branch resulting from resonance below saturation, indicating high quality Fe in these samples. Growth temperature has minimal influence on the observed anisotropy energies.
Anomalous Hall effect in anatase Ti1−xCoxO2−δ above room temperature
Authors: Ueno K. , Fukumura T. , Toyosaki H. , Nakano M. , Yamasaki T. , Yamada Y. , Kawasaki M.
Published: February 2008

Presence of spin polarized electrons was confirmed by observing anomalous Hall effect in a ferromagnetic semiconductor anatase Ti1−xCoxO2−δ up to 600K. The anomalous Hall resistivity exhibited apparent ferromagnetic hysteresis loop from 300to600K with insignificant change in the magnitude, indicating that the Curie temperature is higher than 600K. The measurements above 500K induced an annealing effect represented by the decrease in resistivity, whereas kept the anomalous Hall resistivity nearly constant.
Optimization of the magnetic noise and sensitivity of giant magnetoimpedance sensors
Authors: Melo L. G. C. , Ménard D. , Yelon A. , Ding L. , Saez S. , Dolabdjian C.
Published: February 2008

The performance of magnetic field sensors based upon the giant magnetoimpedance (GMI) effect in soft magnetic wires is investigated in the MHz frequency range. The performance of the sensor is based on its sensitivity, voltage noise level and (voltage) noise-to-sensitivity ratio, or intrinsic magnetic noise level. Optimization of the sensitivity and noise response of the sensor through variation of the sample anisotropy direction and external applied axial field and dc bias current suggest an intrinsic noise level in the fT/Hz level. Qualitative agreement is obtained between theory and experiment on a CoFeSiB microwire, for the maximum sensitivity and the corresponding noise, as a function of the external field and dc bias current.
Aerobic exercise training versus the aetiology of insulin resistance
Authors: Yeo Sophie E. , Coker Robert H.
Published: February 2008

Type 2 diabetes represents an epidemic disease that has become a widespread healthcare problem throughout the world. The prevalence of a sedentary lifestyle and excess caloric intake promotes the aetiology of insulin resistance that results in the development of the metabolic condition, Type 2 diabetes. Despite numerous investigations that have demonstrated the positive influence of aerobic exercise training on a reduction in the severity of insulin resistance, many of these exercise programmes yield benefits that are only short‐lived and promote only modest reductions in the severity of the disease aetiology. Therefore, the efficacy of exercise training as a therapeutic intervention against the development of Type 2 diabetes rests on its ability to normalize insulin resistance in the liver and skeletal muscle using a progressive approach that combines the beneficial influences of exercise training and weight loss.
The influence of beam position and swimming direction on fish target strength
Authors: Henderson M. J. , Horne J. K. , Towler R. H.
Published: February 2008

Henderson, M. J., Horne, J. K., and Towler, R. H. 2007. The influence of beam position and swimming direction on fish target strength. – ICES Journal of Marine Science, 65: 226–237. Fish orientation is consistently identified as a major influence on fish target strength (TS). Generally, orientation is defined as the tilt angle of the fish with respect to the acoustic transducer, whereas a more accurate definition includes tilt, roll, and yaw. Thus far, the influences of roll and yaw on fish TS have only been examined cursorily. We used in situ single-target data to create fish tracks, to estimate fish tilt and yaw, and correlated these estimates with TS. The results show that tilt, yaw, and beam position have a significant influence on fish TS. To investigate further how yaw and beam position affect TS, we calculated the expected backscatter from each fish within simulated fish aggregations using a backscatter model. The TS of individual fish at 38 and 120 kHz varied by as much as 11 and 19 dB with changes in yaw and beam position. Altering the fish’s tilt, yaw, and beam position resulted in TS differences of 14 and 26 dB at 38 and 120 kHz, respectively. Orientation had a minimal influence on an aggregation’s average TS if the aggregation had a variable tilt-angle distribution and was dispersed throughout the acoustic beam.
Estimates for local and movement-based transmission of bovine tuberculosis in British cattle
Authors: Green Darren M , Kiss Istvan Z , Mitchell Andrew P , Kao Rowland R
Published: February 2008

Both badgers and livestock movements have been implicated in contributing to the ongoing epidemic of bovine tuberculosis (BTB) in British cattle. However, the relative contributions of these and other causes are not well quantified. We used cattle movement data to construct an individual (premises)-based model of BTB spread within Great Britain, accounting for spread due to recorded cattle movements and other causes. Outbreak data for 2004 were best explained by a model attributing 16% of herd infections directly to cattle movements, and a further 9% unexplained, potentially including spread from unrecorded movements. The best-fit model assumed low levels of cattle-to-cattle transmission. The remaining 75% of infection was attributed to local effects within specific high-risk areas. Annual and biennial testing is mandatory for herds deemed at high risk of infection, as is pre-movement testing from such herds. The herds identified as high risk in 2004 by our model are in broad agreement with those officially designated as such at that time. However, border areas at the edges of high-risk regions are different, suggesting possible areas that should be targeted to prevent further geographical spread of disease. With these areas expanding rapidly over the last decade, their close surveillance is important to both identify infected herds quickly, and limit their further growth.
Precisely proportioned: intertidal barnacles alter penis form to suit coastal wave action
Authors: Neufeld Christopher J , Palmer A. Richard
Published: February 2008

For their size, barnacles possess the longest penis of any animal (up to eight times their body length). However, as one of few sessile animals to copulate, they face a trade-off between reaching more mates and controlling ever-longer penises in turbulent flow. We observed that penises of an intertidal barnacle (Balanus glandula) from wave-exposed shores were shorter than, stouter than, and more than twice as massive for their length as, those from nearby protected bays. In addition, penis shape variation was tightly correlated with maximum velocity of breaking waves, and, on all shores, larger barnacles had disproportionately stouter penises. Finally, field experiments confirmed that most of this variation was due to phenotypic plasticity: barnacles transplanted to a wave-exposed outer coast produced dramatically shorter and wider penises than counterparts moved to a protected harbour. Owing to the probable trade-off between penis length and ability to function in flow, and owing to the ever-changing wave conditions on rocky shores, intertidal barnacles appear to have acquired the capacity to change the size and shape of their penises to suit local hydrodynamic conditions. This dramatic plasticity in genital form is a valuable reminder that factors other than the usual drivers of genital diversification—female choice, sexual conflict and male–male competition—can influence genital form.
A link between sound producing musculature and mating success in Atlantic cod
Authors: Rowe S. , Hutchings J. A.
Published: February 2008

Individual variability in the mating success of male Atlantic cod Gadus morhua was quantified within an aggregation (n= 59) breeding undisturbed in a large (684 m3) mesocosm tank. Observational and morphometric data were examined to assess the degree to which this mating variation could be explained by aspects of morphology, condition and spawning behaviour. The number of ventral mounts initiated (i.e. mating success) was highly variable; most mounts were initiated by a very small percentage of available males. The significant correlate of male mating success was mass of the sound producing musculature, i.e. drumming muscles. Neither body size, condition, pelvic and median fin morphology nor aggression influenced the number of ventral mounts initiated by a male. The present study suggests a possible link between sound production and mating success in Atlantic cod.
Microhabitat selection in the early juvenile mudskipper Boleophthalmus pectinirostris (L.)
Authors: Chen S. X. , Hong W. S. , Su Y. Q. , Zhang Q. Y.
Published: February 2008

Using laboratory choice experiments, behavioural preferences of the early juvenile mudskipper Boleophthalmus pectinirostris for temperature, salinity and sediment were observed. The temperature preference experiments were conducted in an annular chamber with a thermal gradient of 27 to 34° C, and the fish selected a mean ±s.d. temperature of 31·2 ± 0·5° C. The salinity preference experiments were conducted in an aquarium with decreasing salinity from 20 to 15, 10, 5 and 0·5, and significantly more (P < 0·05) fish were found in water with a salinity of 5. The sediment preference experiments were tested in circular tanks which contained four types of sediment (medium sand, fine sand, muddy sand and sandy mud), and the fish showed a clear preference for sandy mud. These results indicated that early juvenile B. pectinirostris showed behavioural preference for microhabitats. Temperature and salinity probably set large‐scale boundaries on distribution, but sediment should be a critical factor for determining the distribution of the mudskipper.
Polymorphisms of cytochrome b gene in Leishmania parasites and their relation to types of cutaneous leishmaniasis lesions in Pakistan
Authors: MYINT Chomar Kaung , ASATO Yutaka , YAMAMOTO Yu‐ichi , KATO Hirotomo , BHUTTO Abdul M. , SOOMRO Farooq R. , MEMON Muhamad Z. , MATSUMOTO Jun , MARCO Jorge D. , OSHIRO Minoru , KATAKURA Ken , HASHIGUCHI Yoshihisa , UEZATO Hiroshi
Published: February 2008

The exact species and/or strains of Leishmania parasites involved strongly influence the clinical and epidemiological features of leishmaniasis, and current knowledge of those influences and relationships is inadequate. We report that cytochrome b (cyt b) gene sequencing identified causal Leishmania parasites of 69 cutaneous leishmaniasis cases in Pakistan over a 3‐year period. Of 21 cases in highland areas (Quetta city, Balochistan province), 16 (76.2%) were identified as Leishmania (L.) tropica and five (23.8%) as Leishmania (L.) major. Of 48 cases from lowland areas, cities/villages in Indus valley in Sindh and Balochistan provinces, 47 (97.9%) were identified as L. (L.) major and one (2.1%) as L. (L.) tropica. Statistical analysis (Fisher's exact test) revealed a significant difference (P < 0.0001) in the distribution of the two species by altitude; L. (L.) major is predominant in lowland and L. (L.) tropica at highland areas. The present result enriched our earlier finding, based on the first year's cultured parasite data, that only L. (L.) tropica was found in highland areas and only L. (L.) major in lowland areas. Among Leishmania samples analyzed, three types of cyt b polymorphism of L. (L.) major were found, including 45 (86.5%) cases of type I, six (11.5%) of type II and one (2%) of type III. We report for the first time on the presence of polymorphisms in L. (L.) major (types I, II and III) based on species identification using cyt b gene sequencing from clinical samples. Moreover, we found no correlation between clinical presentation (wet‐, dry‐ and/or mixed‐types of cutaneous lesions) and causal Leishmania parasites.
Experimental pseudocyst model resembling human ganglion
Authors: TANIGUCHI Toshiko , HARADA Teruichi , OHBA Norihiro , MOTOMURA Hisashi , MAEDA Mitsuyo , ISHII Masamitsu
Published: February 2008

There is no animal model of ganglion. We describe a simple and reproducible animal model of pseudocystic diseases. First, we experimented to establish a pseudocystic model. We used cylindrical glass implants (6 mm diameter, 30 mm long) to create fibrous capsules in rats. The implants were inserted in the subcutaneous tissue in the dorsum of rats. Sixty implants were carried out (two implants per rat). Twelve weeks after implantation, the glass implants were removed and 0.5 mL sodium hyaluronate solution was injected into each cavity. Next, we tested the model by histological examination after OK‐432 administration. Microscopic examination revealed that the wall was composed of a layer of collagenous fibers similar to those noted in ganglia; the lumen was retained for 3 weeks. Histopathological changes after OK‐432 administration showed nonspecific inflammatory response induced by OK‐432, resulting in in vivo activation of many inflammatory cells and then fast and reliable closure of cavities. No harmful reactions to OK‐432 were observed histopathologically. These data suggest that our experimental cyst is a suitable model for studying pseudocystic diseases. This model can be used for research evaluating safe drug doses, conducting therapeutic comparison of several agents, and histopathological time course studies of the affected tissues. OK‐432 administration on this model showed the potential of one of the ideal agents to treat pseudocystic lesions like ganglion.
Desmoplastic fibroblastoma (collagenous fibroma)
Authors: WATANABE Hirokazu , ISHIDA Yusuke , NAGASHIMA Kazuo , MAKINO Teruhiko , NORISUGI Osamu , SHIMIZU Tadamichi
Published: February 2008

Desmoplastic fibroblastoma (DF) is a rare fibrotic tumor that has a wide anatomic distribution and it can appear in deep sections of the subcutis, in fascia, in aponeurosis or in skeletal muscles. This report describes a case of DF that appeared on the left side of the neck of a 55‐year‐old male as a 3.5‐cm solitary, firm nodule. Histologically, it was composed of stellate or bland spindle‐shaped cells embedded in a loose collagenous stroma. The entrapment of fat and muscle tissues was focally identified at the edges of the tumor. The stellate and multinucleated cells in the lesion were strongly positive for vimentin but negative for cytokeratin, smooth muscle actin, desmin, S‐100, CD34, factor XIIIa, and CD68. These findings suggest that the stellate and multinucleated cells in the lesion were of fibroblastic origin and this neoplasm was pathologically benign.
Cutaneous mucinous nodule in a patient with rheumatoid arthritis
Authors: HONDA Akio , FUJIMOTO Eita , KURODA Kei , TAJIMA Shingo
Published: February 2008

We report a cutaneous mucinous nodule on the inflamed elbow joint in a patient with rheumatoid arthritis (RA). The lesion is clinically characterized by a continuous flow of mucinous exudates from the nodule, and histologically by an extensive mucin deposition and proliferations of the fibroblastic cells and mononuclear cells. The histological findings suggest the histogenesis of this unique nodule is related to extralesional proliferation of synovial lining cells consisting of monocyte–macrophage lineage cells and fibroblast‐like cells which potentially produce synovial fluid. Four patients have been hitherto reported in the published work and all of them have been associated with RA. The condition may be one of the characteristic skin manifestations of RA.
Steroid‐resistant adult‐onset Still's disease which showed a quick response to methotrexate
Authors: OKAMOTO Osamu , OISHI Masaki , FUJIWARA Sakuhei
Published: February 2008

A case of steroid‐resistant adult‐onset Still's disease is herein reported. The patient consulted us because of night fever, arthralgia and evanescent rashes. She was diagnosed with adult‐onset Still's disease, with a C‐reactive protein (CRP) value of 29.5 mg/dL and serum ferritin level of 4500 ng/mL. The fever, rashes and arthralgia disappeared after medication of medium‐dose oral prednisolone, however, the CRP value persisted at high levels, and the serum ferritin level nevertheless increased by 5200 ng/mL. Following the pulse therapy with corticosteroid, the CRP value decreased once but thereafter returned to a high level again. The serum ferritin level did not respond during that therapy. Finally, 10 days after starting the administration of methotrexate, the CRP value dramatically decreased from 7 mg/dL to 0.16 mg/dL, and thereafter the serum ferritin level started to decline, which thus enabled us to eventually taper the dose of oral prednisolone.
Chronic ethanol intake promotes double gluthatione S‐transferase/transforming growth factor‐α‐positive hepatocellular lesions in male Wistar rats
Authors: Pires Paulo Wagner , Furtado Kelly Silva , Justullin Luis Antonio , Rodrigues Maria Aparecida Marchesan , Felisbino Sergio Luis , Barbisan Luis Fernando
Published: February 2008

The chronic ethanol intake influence on the gluthatione S‐transferase (GST‐P) and transforming growth factor α (TGF‐α) expression in remodeling/persistent preneoplastic lesions (PNLs) was evaluated in the resistant hepatocyte model. Male Wistar rats were allocated into five groups: G1, non‐treated, fed water and chow ad libitum; G2, non‐treated and pair‐fed chow (restricted to match that of G3 group) and a maltodextrin (MD) solution in tap water (matched ethanol‐derived calories); G3, fed 5% ethanol in drinking water and chow ad libitum; G4, diethylnitrosamine (DEN, 200 mg/kg, body weight) plus 200 parts per million of 2‐acetylaminofluorene (2‐AAF) for 3 weeks and pair‐fed chow (restricted to match that of G5 group) and an MD solution in tap water (matched ethanol‐derived calories); G5, DEN/2‐AAF treatment, fed ethanol 5% and chow ad libitum. All animals were subjected to 70% partial hepatectomy at week 3 and sacrificed at weeks 12 or 22, respectively. Liver samples were collected for histological analysis or immunohistochemical expression of GST‐P, TGF‐α and proliferating cell nuclear antigen or zymography for matrix metalloproteinases‐2 and ‐9. At the end of ethanol treatment, there was a significant increase in the percentage of liver area occupied by persistent GST‐P‐positive PNLs, the number of TGF‐α‐positive PNLs and the development of liver tumors in ethanol‐fed and DEN/2‐AAF‐treated groups (G5 versus G4, P < 0.001). In addition, ethanol feeding led to a significant increase in cell proliferation mainly in remodeling and persistent PNLs with immunoreactivity for TGF‐α at week 22 (P < 0.001). Gelatinase activities were not altered by ethanol treatment. The results demonstrated that ethanol enhances the selective growth of PNL with double expression of TGF‐α and GST‐P markers. (Cancer Sci 2008; 99: 221–228)
Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population
Authors: Tao Hong , Shinmura Kazuya , Suzuki Masaya , Kono Suminori , Mibu Ryuichi , Tanaka Masao , Kakeji Yoshihiro , Maehara Yoshihiko , Okamura Takeshi , Ikejiri Kouji , Futami Kitaroh , Yasunami Youichi , Maekawa Takafumi , Takenaka Kenji , Ichimiya Hitoshi , Imaizumi Nobutoshi , Sugimura Haruhiko
Published: February 2008

The MUTYH gene encodes a DNA glycosylase that can initiate the base excision repair pathway and prevent G:C > T:A transversion by excising adenine mispaired with 8‐hydroxyguanine. Biallelic germline mutations of MUTYH have been shown to predict familial and sporadic multiple colorectal adenomas and carcinomas, however, whether there is an association between single nucleotide polymorphisms (SNPs) of MUTYH and sporadic colorectal cancer (CRC) risk has remained unclear. In this study we investigated four MUTYH SNPs, IVS1+11C > T, IVS6+35G > A, IVS10–2A > G, and 972G > C (Gln324His), for an association with increased CRC risk in a population‐based series of 685 CRC patients and 778 control subjects from Kyushu, Japan. A statistically significant association was demonstrated between IVS1+11T and increased CRC risk (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.012–2.030; P = 0.042) and one of the five haplotypes based on the four SNPs, the IVS1+11T – IVS6+35G – IVS10–2A – 972C (TGAC) haplotype containing IVS1+11T, was demonstrated to be associated with increased CRC risk (OR, 1.43; 95% CI, 1.005–2.029; P = 0.046). Subsite‐specific analysis showed that the TGAC haplotype was statistically significantly (P = 0.013) associated with an increased risk of distal colon, but not proximal colon or rectal cancer. Furthermore, IVS1+11C > T was found to be in complete linkage disequilibrium with –280G > A and 1389G > C (Thr463Thr). The results indicated that Japanese individuals with – 280A/IVS1+11T/1389C genotypes or the TGAC haplotype are susceptible to CRC. (Cancer Sci 2008; 99: 355–360)
Involvement of protein kinase C β–extracellular signal‐regulating kinase1/2/p38 mitogen‐activated protein kinase–heat shock protein 27 activation in hepatocellular carcinoma cell motility and invasion
Authors: Guo Kun , Liu Yinkun , Zhou Haijun , Dai Zhi , Zhang Jubo , Sun Ruixia , Chen Jie , Sun Qianglin , Lu Wenjing , Kang Xiaonan , Chen Pei
Published: February 2008

To understand the molecular mechanism that underlies the role of various prominent signal pathways in hepatocellular carcinoma (HCC) metastasis, a human signal transduction oligonucleotide microarray analysis was carried out in cultured HCC cell models with increasing spontaneous metastatic potential (MHCC97L, MHCC97H, and HCCLM6). The results revealed that the mitogen‐activated protein kinase (MAPK) pathway is the prominently upregulated pathway in HCC metastasis. Further study showed that basal phosphorylated levels of extracellular signal‐regulating kinase (ERK)1/2 and p38 MAPK consecutively increased from MHCC97L to MHCC97H to HCCLM6 cells, but not c‐Jun N‐terminal kinase. The phosphorylation of ERK1/2 and p38 MAPK was regulated by upregulated protein kinase Cβ (PKCβ) in HCC cells through the integrated use of PKCβ RNA interference, the PKCβ specific inhibitor enzastaurin and a PKC activator phorbol‐12‐myristate‐13‐acetate. Heat shock protein 27 (HSP27) was also verified as a downstream common activated protein of PKCβ–ERK1/2 and PKCβ–p38 MAPK. In vitro migration and invasion assay further showed that the depletion of PKCβ or inhibition of PKCβ activation effectively decreased HCC cell motility and invasion. Moreover, the motility and invasion of phorbol‐12‐myristate‐13‐acetate‐stimulated PKCβ‐mediated HCC cells was significantly negated by an ERK inhibitor, 1.4‐diamino‐2.3‐dicyano‐1.4‐bis[2‐aminophenylthio] butadiene, or a p38 MAPK inhibitor, 4‐(4‐Fluorophenyl)‐2‐(4‐methylsulfinylphenyl)‐5‐(4‐pyridyl)1H‐imidazole. It also showed that HSP27 is critical in PKCβ‐mediated HCC cell motility and invasion. Taken together, this study reveals the important role of this PKCβ‐ERK1/2/p38MAPK‐HSP27 pathway, which was verified for the first time, in modulating HCC cell motility and invasion. (Cancer Sci 2008; 99: 486–496)
Development of glutathione S‐transferase‐P‐negative foci accompanying nuclear factor‐erythroid 2‐related factor 2 expression during early stage of rat hepatocarcinogenesis
Authors: Fan Yang , Shimizu Takeshi , Yamada Toshiyuki , Nanashima Naoki , Akita Miki , Asano Jumpei , Tsuchida Shigeki
Published: February 2008

Glutathione S‐transferase P (GST‐P), a marker for rat hepatic preneoplastic lesions, is suggested to bind to Jun N‐terminal kinase (JNK) to repress stress response, and GST‐P gene expression is regulated by a transcription factor, nuclear factor‐erythroid 2‐related factor 2 (Nrf2). In this study, we examined by immunohistochemistry whether JNK2, p38 mitogen‐activated protein kinase, and Nrf2 were expressed in GST‐P‐positive foci induced by the Solt–Farber protocol. At 2 weeks after partial hepatectomy, all GST‐P‐positive foci were negative for p38, and 86.4 ± 5.6% and 64.7 ± 6.3% of GST‐P‐positive foci were negative for JNK2 and Nrf2, respectively. Western blot analysis showed decreased p38 mitogen‐activated protein kinase and JNK2 expression in livers treated with the protocol. In immunohistochemistry, besides GST‐P‐positive foci, GST‐P‐negative foci were detected as p38‐negative foci in the surrounding tissues positive for p38. In contrast to GST‐P‐positive foci, most GST‐P‐negative foci showed enhanced Nrf2 expression. The number of GST‐P‐negative foci was 76 ± 18/10 mm2 of liver section at 2 weeks, but was undetectable at 1 week. The area of GST‐P‐negative foci was 0.09 ± 0.05 mm2, smaller than that of GST‐P‐positive ones (0.29 ± 0.23). After treatment with carbon tetrachloride, small vacuoles due to liver injury were frequently observed inside GST‐P‐negative foci but less frequently in GST‐P‐positive foci. However, this treatment resulted in expression of JNK2, p38, and Nrf2 in both foci. These results showed development of GST‐P‐negative foci during the early stage of hepatocarcinogenesis and suggested that Nrf2 is not responsible for GST‐P expression in rat hepatic preneoplastic foci. (Cancer Sci 2008; 99: 497–501)
Smoking status of step‐parents as a risk factor for smoking in adolescence
Authors: Fidler Jennifer A. , West Robert , Van Jaarsveld Cornelia H. M. , Jarvis Martin J. , Wardle Jane
Published: February 2008

Aim  To examine the extent to which smoking by step‐parents and biological parents predicts adolescent smoking.

Design  Five‐year cohort study.

Setting  Thirty‐six schools in South London, England.

Participants  A subset of 650 students participating in the Health and Behaviour In Teenagers Study (HABITS), who reported living in step‐families, were assessed annually from age 11–12 to age 15–16 years.

Measurements  Students reported their smoking status, which was cotinine‐verified, as well as whether their parents smoked and, if they lived with a step‐parent, whether that step‐parent smoked. Analyses also controlled for gender, ethnicity and deprivation.

Findings  Students who reported that just their step‐parent smoked at age 11–12 were significantly more likely to report current smoking at any time‐point from age 11–16 than those who reported having neither biological parents nor a step‐parent who smoked [odds ratio (OR) 2.72, 95% confidence interval (CI) = 1.36–5.47], as were those with both a parent and a step‐parent who smoked (OR 2.23, 95% CI = 1.46–3.41). While the association between smoking in students and smoking in biological parents in this subsample did not reach statistical significance (OR 1.39, 95% CI = 0.88–2.19), these students were no more or less likely to smoke than those with just a step‐parent who smoked.

Conclusion  Smoking by a non‐biological parent appears at least as influential as smoking by biological parents. This confirms the importance of social influence on smoking initiation and suggests that attempts to work with parents in smoking prevention should involve, and perhaps pay particular attention to, step‐parents who smoke.
Seasonal changes in antigen‐specific T‐helper clone sizes in patients with Japanese cedar pollinosis: a 2‐year study
Authors: Horiguchi S. , Tanaka Y. , Uchida T. , Chazono H. , Ookawa T. , Sakurai D. , Okamoto Y.
Published: February 2008

Background
Allergic rhinitis (AR) is a typical type I allergic disease that occurs through the induction of allergen‐specific effector T cells. Once established, new effector T cells derive mostly from memory T cells that are capable of surviving for extended periods, although the mechanisms by which these memory functions are maintained have not yet been clarified. In particular, the exact life‐span of memory T cells is still not well understood.

Objective
Pollinosis patients seemed to be suitable subjects to investigate because such patients are exposed to antigens strongly for only a limited period once a year. We compared the seasonal changes in memory T‐helper type 2 (Th2) between pollinosis and perennial allergic subjects.

Methods
The clone sizes of the Japanese cedar pollen‐specific memory Th cells were measured by an ELISPOT assay using specific peptides from the patients with cedar pollinosis, and the seasonal changes were noted. This study was performed for 2 years. The cedar‐specific IgE levels in the peripheral blood were also studied. Mite allergy patients were also enrolled in the study.

Results
The Japanese cedar‐specific IL‐4‐producing Th2 cells were detected in all patients examined, although the number of cells was low. These Th memory cells increased during the pollen season and decreased during the off‐season. However, more than 60% of the cedar‐specific memory Th2 cells survived up to 8 months after the pollen season. The cedar‐specific IgE levels exhibited changes similar to the cedar‐specific Th cells. On the other hand, there was no drifting of Th memory clone size with the mite allergics, and the IgE levels also did not change.

Conclusions
While pollen‐specific Th cells decreased after pollen exposure, their memory functions continued. Memory clone size maintenance therefore requires repetitive antigen irritation.
Associations of FcɛRIβ E237G polymorphism with wheezing in Taiwanese schoolchildren
Authors: Lee Y‐L. , Gilliland F. D. , Wang J‐Y. , Lee Y‐C. , Guo Y. L.
Published: February 2008

Background
The β‐chain of a high‐affinity IgE receptor (FcɛRIβ) has been proposed as a candidate gene for atopic diseases, but previous studies have come to inconsistent conclusions. Because some air pollutants would produce oxidative stress, increase serum IgE, and trigger T‐helper type 2 (Th2)‐type airway inflammation, the associations of FcɛRIβ polymorphism with wheezing illness may vary by their exposures and variants of oxidant defence genes. The purpose of this study was to investigate the association of FcɛRIβ E237G polymorphism with wheezing illness and to determine whether these associations vary with air pollution and glutathione S‐transferase (GST) P1‐105 and M1 genotypes.

Methods
In 2001, we conducted a case–control study comprised of 214 children with any history of wheezing and 185 non‐wheezing controls, all of whom were selected from 2558 fourth‐ to ninth‐grade schoolchildren in southern Taiwan. We examined differences in associations with ambient air pollution and by GST genotypes.

Results
Compared with the FcɛRIβ EE genotype, children with the G allele had a significantly reduced risk of lifetime wheezing with low‐ozone exposure [adjusted odds ratio (aOR)=0.25, 95% confidence interval (CI) 0.08–0.69]. The risk was not reduced in children living in high‐ozone communities (aOR=0.98, 95% CI 0.57–1.67). This difference in genotypic effects between low‐ and high‐pollution environments was statistically significant. The reduction of the protective effect from the G allele with higher air pollution was most marked in the GSTP1‐105 Ile/Val or Val/Val and GSTM1 null groups.

Conclusion
The FcɛRIβ E237G allele may have a protective role in wheezing illness among Taiwanese schoolchildren, depending on airway oxidative stress levels.
Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes
Authors: Pillai S. G. , Tang Y. , Van Den Oord E. , Klotsman M. , Barnes K. , Carlsen K. , Gerritsen J. , Lenney W. , Silverman M. , Sly P. , Sundy J. , Tsanakas J. , Von Berg A. , Whyte M. , Ortega H. G. , Anderson W. H. , Helms P. J.
Published: February 2008

Background
Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression.

Objective
To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors.

Methods
Probands aged 7–35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT).

Results
Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self‐reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's α ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC20, age and asthma severity (interrupted sleep). IgE correlated with all three atopy‐related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma.

Conclusion
In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.