bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of future climate change on seasonal discharge, hydrological processes and extreme flows in the Upper Wye experimental catchment, Mid‐Wales
Authors: Pilling C. G. , Jones J. A. A.
Published: October 2002

Analysing the impact of future climate change on hydrological regimes is hampered by the disparity of scales between general circulation model (GCM) output and the spatial resolution required by catchment‐scale hydrological simulation models. In order to overcome this, statistical relationships were established between three indices of atmospheric circulation (vorticity and the strength and direction of geostrophic windflow) and daily catchment precipitation and potential evapotranspiration (PET) to downscale from the HadCM2 GCM to the Upper Wye experimental catchment in mid‐Wales. The atmospheric circulation indices were calculated from daily grid point sea‐level pressure data for: (a) the Climatic Research Unit observed data set (1975–90); (b) the HadCM2SUL simulation representing the present climate (1980–99); and (c) the HadCM2SUL simulation representing future climate conditions (2080–99). The performance of the downscaling approach was evaluated by comparing diagnostic statistics from the three downscaled precipitation and PET scenarios with those recorded from the Upper Wye catchment. The most significant changes between the downscaled HadCM2SUL 1980–99 and 2080–99 scenarios are decreases in precipitation occurrence and amount in summer and autumn combined with a shortening of mean wet spell length, which is most pronounced in autumn. A hydrological simulation model (HYSIM) was calibrated on recorded flow data for the Upper Wye catchment and ‘forced’ with the three downscaled precipitation and PET scenarios to model changes in river flow and hillslope hydrological processes. Results indicate increased seasonality of flows, with markedly drier summers. Analysis of extreme events suggests significant increases in the frequency of both high‐ and low‐flow events. Copyright © 2002 John Wiley & Sons, Ltd.
Plagioclase weathering in the groundwater system of a sandy, silicate aquifer
Authors: Kim Kangjoo
Published: October 2002

The weathering rate of plagioclase was estimated in the groundwater system of a sandy, silicate aquifer formed after the Wisconsin Glacial Stage. The study area is an isthmus lying between Crystal and Big Muskellunge Lakes in northern Wisconsin, USA. Plagioclase occupies 3% of the quartz and K‐feldspar dominated sediments. Groundwater in the study area is recharged in part by precipitation through the isthmus soils and in part by seepage from Crystal Lake, which is of low ionic strength and chemically in steady state. Water analysis revealed that the chemistry of groundwater recharged from Crystal Lake is regulated by mineral dissolution reactions. The rate constant for plagioclase was estimated using mass balances for sodium concentrations along a groundwater flowline from Crystal Lake. For this calculation, various kinds of hydrological/mineralogical information were used: groundwater flow path from oxygen isotope analysis, groundwater travel times from flow modelling, mineral composition from microprobe analysis and surface area of minerals from BET (Brunauer–Emmett–Teller) analysis. The overall range of the estimation was less than an order of magnitude (3·5 × 10−16 to 3·4 × 10−15 mol/m2/s). The result is up to three orders of magnitude slower than the previous field estimates, which applied geometric methods in measuring mineral surface areas. However, this result is somewhat higher than the estimates reported by other BET area‐based studies, which were undertaken on soil profiles having different hydrological conditions. This rate difference is interpreted as a result of higher mineral reactivity owing to younger sediment age. The rate difference is smaller when this result is compared with the estimates from the soils of similar age, indicating that the differences in hydrological condition are not sufficient to explain the weathering rate discrepancy between the laboratory and field studies, which is up to five orders of magnitude. Copyright © 2002 John Wiley & Sons, Ltd.
Geometric Brownian motion as a model for river flows
Authors: Lefebvre Mario
Published: October 2002

Let X(t) be the flow of a certain river at time t. A geometric Brownian motion process is used as a model for X(t) and is found to give very good forecasts of future flows. The forecasted values generated by this one‐dimensional model are compared with those provided by a deterministic model that requires the evaluation of 18 entries. Based on two important criteria, the stochastic model is superior, on average, to the deterministic model for forecasts up to 4 days ahead. Copyright © 2002 John Wiley & Sons, Ltd.
The influence of autocorrelation on the ability to detect trend in hydrological series
Authors: Yue Sheng , Pilon Paul , Phinney Bob , Cavadias George
Published: October 2002

This study investigated using Monte Carlo simulation the interaction between a linear trend and a lag‐one autoregressive (AR(1)) process when both exist in a time series. Simulation experiments demonstrated that the existence of serial correlation alters the variance of the estimate of the Mann–Kendall (MK) statistic; and the presence of a trend alters the estimate of the magnitude of serial correlation. Furthermore, it was shown that removal of a positive serial correlation component from time series by pre‐whitening resulted in a reduction in the magnitude of the existing trend; and the removal of a trend component from a time series as a first step prior to pre‐whitening eliminates the influence of the trend on the serial correlation and does not seriously affect the estimate of the true AR(1). These results indicate that the commonly used pre‐whitening procedure for eliminating the effect of serial correlation on the MK test leads to potentially inaccurate assessments of the significance of a trend; and certain procedures will be more appropriate for eliminating the impact of serial correlation on the MK test. In essence, it was advocated that a trend first be removed in a series prior to ascertaining the magnitude of serial correlation. This alternative approach and the previously existing approaches were employed to assess the significance of a trend in serially correlated annual mean and annual minimum streamflow data of some pristine river basins in Ontario, Canada. Results indicate that, with the previously existing procedures, researchers and practitioners may have incorrectly identified the possibility of significant trends. Copyright © Environment Canada. Published by John Wiley & Sons, Ltd.
A low‐level penetration seeding experiment of liquid carbon dioxide in a convective cloud
Authors: Wakimizu Kenji , Nishiyama Koji , Suzuki Yoshinori , Tomine Kikuro , Yamazaki Mitsuru , Isimaru Ataru , Ozaki Motoki , Itano Tosihisa , Naito Genichi , Fukuta Norihiko
Published: October 2002

In order to bring large amounts of precipitation, the new seeding method using liquid carbon dioxide (LC) was suggested by Fukuta (1996a). The method was applied to the supercooled convective cloud in a post‐frontal weather condition in northern Kyushu, Japan, on October 27 1999. In the seeding experiment, LC seeding and the subsequent observation by aircraft were carried out and the features of a seeded echo were observed by radar. Consequently, the aircraft observation confirmed the further development of the seeded cumulus together with a fuzzy aspect of the cloud surface, which indicates the feature consisting of ice particles. Furthermore, the observed cloud top was quite consistent with the cloud top estimated by the thermodynamic analysis following parcel theory. Therefore, the observed results indicate the artificial effects by LC seeding. On the other hand, the radar observation confirmed an artificially induced echo, which showed spreading of the echo area and took a unique mushroom shape in the RHI pictures. The maximum width of the echo reached 24 km and the total amount of estimated radar precipitation of the seeded cumulus was approximately 2.4 million ton, traversing a distance of 60 km in 1 h 40 min. The observed and estimated results are consistent with the hypothesis of the new seeding method, which induces the dynamic and microphysical processes consisting of two fundamental processes. In addition, it was found that dynamical interaction between the seeded and the adjacent natural cumuli was an important factor in the formation of the secondary cumulus. The observational fact will give new viewpoint into the future seeding study. Copyright © 2002 John Wiley & Sons, Ltd.
Simulating hydrological response for the R‐5 catchment: comparison of two models and the impact of the roads
Authors: Loague Keith , VanderKwaak Joel E.
Published: October 2002

In this paper the performance of two hydrological‐response models is evaluated and compared based upon simulations for a single rainfall–runoff event. The two models are QPBRRM, a relatively simple model of Horton overland flow, and InHM, a comprehensive physics‐based model of each of the known streamflow generation mechanisms. The rainfall–runoff event focused upon in this study is from the small rangeland catchment in Oklahoma known as R‐5. When calibrated, both QPBRRM and InHM are shown to effectively simulate the R‐5 event. The calibration procedures used in this study for QPBRRM and InHM were quite different. The calibration of QPBRRM was a curve fitting exercise, whereas the calibration of InHM was based upon an internally valid estimate of the continuous head field. In this study QPBRRM did not perform well outside of the calibrated range. The impact of the roads cutting across the R‐5 catchment is simulated with InHM and discussed for the first time in the study reported here. The relative merits of QPBRRM and InHM are each discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Heuristic numerical and analytical models of the hydrologic controls over vertical solute transport in a domed peat bog, Jura Mountains, Switzerland
Authors: McKenzie Jeffrey M. , Siegel Donald I. , Shotyk William , Steinmann Philipp , Pfunder Gabriele
Published: October 2002

We report the results of numerical and analytical simulations to test the hypothesis that downward vertical flow of porewater from the crests of domed alpine and kettle bogs controls vertical porewater distributions of major solutes such as Ca and Mg. The domed Etang de la Gruère bog (EGr), Switzerland, characterized by a vertical downward gradient of 0·04 and stratified layers of peat, is chosen as a field site for the model calibration and evaluation. The middle 4‐m section of the 6·5 m thick bog peat is heavily humified and has a hydraulic conductivity of ∼10−5·6 cm s−1. Above and below, peat is less humified with a hydraulic conductivity of ∼10−3 cm s−1. Heuristic finite difference simulations, using Visual MODFLOW, of the bog hydraulics show that the higher conductivity peat at the bog base is critical to create the observed deep, local flow cells that substantively recharge porewater.

Model results and Peclet number calculations show that before ∼7000 14C yr BP diffusion of solutes from underlying mineral soils controlled the vertical distribution of porewater chemistry. From 7000 to ∼1250 14C BP the porewater chemistry was probably controlled by both upward diffusion and downward advection, and after ∼1250 14C yr BP porewater chemistry was probably controlled by downward advection. Concentrations of conservative major solutes in the porewaters of alpine, ombrotrophic bogs are the net effect of both downward vertical porewater movement and upward vertical diffusion, the magnitudes of which are delicately poised to the configuration of the bog water table over time and subsurface peat stratigraphy. Copyright © 2002 John Wiley & Sons, Ltd.
Tracer properties of eroded sediment and source material
Authors: Motha J. A. , Wallbrink P. J. , Hairsine P. B. , Grayson R. B.
Published: October 2002

This paper examines the conservativeness of tracers through the sediment generation process. This is done by comparing a selection of tracer properties of sediment eroded from large plots by simulated rainfall, with the corresponding properties of the source materials within the plots. Sediment was generated using three simulated rainfall events for each of five selected erosion source types in the Tarago catchment, Victoria, Australia. As there were particle size and organic content differences between the source material and the generated sediment, the measured tracer properties of the source material were corrected for these differences. The possible role of analytical errors in this investigation was also addressed. The geochemical property, concentration of Fe2O3, was not conservative for any of the process sources investigated. Concentration of Al2O3 was not conservative for three of the four process sources investigated, and the sum of molecular proportions of CaO**, Na2O, K2O and Al2O3 was not conservative for two of the four process sources investigated. Mineral magnetic properties, IRM850 and χ were also found to be not conservative, although this may be the result of the complex relationship between particle size and mineral magnetic properties not being adequately accommodated in this analysis. The radionuclide tracers, 137Cs and 210Pbex, were found to be conservative through the sediment generation process. Copyright © 2002 John Wiley & Sons, Ltd.
Estimation of baseflow residence times in watersheds from the runoff hydrograph recession: method and application in the Neversink watershed, Catskill Mountains, New York
Authors: Vitvar Tomas , Burns Douglas A. , Lawrence Gregory B. , McDonnell Jeffrey J. , Wolock David M.
Published: October 2002

A method for estimation of mean baseflow residence time in watersheds from hydrograph runoff recession characteristics was developed. Runoff recession characteristics were computed for the period 1993–96 in the 2 km2 Winnisook watershed, Catskill Mountains, southeastern New York, and were used to derive mean values of subsurface hydraulic conductivity and the storage coefficient. These values were then used to estimate the mean baseflow residence time from an expression of the soil contact time, based on watershed soil and topographic characteristics. For comparison, mean baseflow residence times were calculated for the same period of time through the traditional convolution integral approach, which relates rainfall δ18O to δ18O values in streamflow. Our computed mean baseflow residence time was 9 months by both methods. These results indicate that baseflow residence time can be calculated accurately using recession analysis, and the method is less expensive than using environmental and/or artificial tracers. Published in 2002 by John Wiley & Sons, Ltd.
Refined conceptualization of TOPMODEL for shallow subsurface flows
Authors: Walter M. Todd , Steenhuis Tammo S. , Mehta Vishal K. , Thongs Dominique , Zion Mark , Schneiderman Elliot
Published: October 2002

The TOPMODEL framework was used to derive expressions that account for saturated and unsaturated flow through shallow soil on a hillslope. The resulting equations were the basis for a shallow‐soil TOPMODEL (STOPMODEL). The common TOPMODEL theory implicitly assumes a water table below the entire watershed and this does not conceptually apply to systems hydrologically controlled by shallow interflow of perched groundwater. STOPMODEL provides an approach for extending TOPMODEL's conceptualization to apply to shallow, interflow‐driven watersheds by using soil moisture deficit instead of water table depth as the state variable. Deriving STOPMODEL by using a hydraulic conductivity function that changes exponentially with soil moisture content results in equations that look very similar to those commonly associated with TOPMODEL. This alternative way of conceptualizing TOPMODEL makes the modelling approach available to researchers, planners, and engineers who work in areas where TOPMODEL was previously believed to be unsuited, such as the New York City Watershed in the Catskills region of New York State. Copyright © 2002 John Wiley & Sons, Ltd.
High‐resolution numerical modelling of three‐dimensional flows over complex river bed topography
Authors: Lane S. N. , Hardy R. J. , Elliott L. , Ingham D. B.
Published: October 2002

This paper describes preliminary results from a method for the treatment of complex bed topography for the understanding of three‐dimensional flow processes. It develops an established porosity‐based method and couples it to high‐resolution bed topographical data acquired using digital photogrammetry. The results provide quantitative data on flow processes that match and perhaps exceed current measurement capabilities, and so raise difficult questions for model validation. However, the detailed flow fields provided by the method allow us to develop current models for flow–form interactions in gravel‐bed rivers. Of most importance, the method will allow us to enhance significantly the application of computational fluid dynamics to complex river bed morphology, for large eddy simulation, roughness parameterization, sediment entrainment and deposition studies, and understanding interactions between flow and vegetation in relation to conveyance studies. Copyright © 2002 John Wiley & Sons, Ltd.
Geographic differences in invasive and in situ breast cancer incidence according to precise geographic coordinates, Connecticut, 1991–95
Authors: Gregorio David I. , Kulldorff Martin , Barry Leah , Samociuk Holly
Published: October 2002

To evaluate geographical variation of invasive and in situ breast cancer incidence rates using precise geographical coordinates for place of residence at diagnosis, latitude‐longitude coordinates pertaining to 10,601 invasive and 1,814 in situ breast cancers for Connecticut women, 1991–95, were linked to US Census information on the 2,905State census block groups. A spatial scan statistic was used to detect geographic excess or deficits in incidence and test the statistical significance of results, without prior assumptions about the size or location of such areas. The age adjusted invasive cancer incidence rate was 165.3/100,000 women/year. The spatial scan statistic identified 3 places with significantly low incidence rates and 4 places where rates were significantly high. The most probable location of low incidence was rural northeastern Connecticut where risk of disease, relative to elsewhere around the state, was 0.70 (p = 0.0001); the most probable place of elevated incidence was north central Connecticut where a relative risk of 1.34 (p = 0.002) was observed. Incidence of in situ disease was estimated to be significantly high for north central Connecticut (RR = 1.84; p = 0.0001). Geographic differences of invasive and in situ breast cancer incidence were observed. Examining cancer events at the lowest available level of data aggregation is beneficial in highlighting localized rate variations. Such information may enable public health officials to target additional resources for promoting breast cancer screening to specific locations. © 2002 Wiley‐Liss, Inc.
Involvement of human heat shock protein 90α in nicotine‐induced apoptosis
Authors: Wu Yu‐ping , Kita Kazuko , Suzuki Nobuo
Published: October 2002

There have been conflicting reports of the apoptotic effects of nicotine on human cells and those studies reporting nicotine‐induced apoptosis have not unequivocally clarified the molecular mechanisms underlying the effect. However, we found here that human RSa cells, established from embryonic fibroblastic cells doubly infected with Rous sarcoma virus and Simian virus 40, underwent apoptosis when cultured with medium containing 0.06–0.6 μM nicotine. The apoptosis was assessed by cellular DNA fragmentation and caspase‐3 protease activation. Viability of RSa cells was reduced by nicotine treatment, as analyzed by MTT assay and the reduction was lessened by combination treatment with a caspase‐3 inhibitor, acetyl‐L‐aspartyl‐L‐glutamyl‐L‐valyl‐L‐aspart‐1‐al (Ac‐DEVD‐CHO). Levels of expression of heat shock protein 90α (Hsp90α) were found to be increased 20 min after the nicotine treatment, as analyzed by polymerase chain reaction‐based mRNA differential display after Northern blotting analysis of mRNA amounts. Cellular contents of Hsp90α were furthermore increased in the nicotine‐treated RSa cells, as quantitated by Western immunoblot analysis. By contrast, in RSa cells treated with nicotine in combination with geldanamycin (GA), an inhibitor of Hsp90α function, DNA fragmentation was not detected and caspase‐3 protease activity levels were the same as those of mock‐treated cells. Nicotine‐induced caspase‐3 activation and Hsp90α expression, as well as suppression of the induction by GA, were also observed in a xeroderma pigmentosum patient‐derived cell line, XP2OS cells. Thus, it was suggested that nicotine induces apoptosis, possibly via Hsp90α expression, in human cells tested. © 2002 Wiley‐Liss, Inc.
Extremely potent, rapid and costimulation‐independent cytotoxic T‐cell response against lymphoma cells catalyzed by a single‐chain bispecific antibody
Authors: Dreier Torsten , Lorenczewski Grit , Brandl Christian , Hoffmann Patrick , Syring Uwe , Hanakam Frank , Kufer Peter , Riethmuller Gert , Bargou Ralf , Baeuerle Patrick A.
Published: October 2002

A recent study reported on an anti‐CD19/anti‐CD3 single‐chain bispecific antibody (bscCD19xCD3) exhibiting high activity against human B lymphoma cell lines (Löffler et al., Blood 2000;95:2098–103). In the present study, we have explored in detail the in vitro efficacy, T‐cell donor variability, binding characteristics, specificity, kinetics and interleukin‐2 (IL‐2) dependence of bscCD19xCD3. We found that a majority of human donor T cells tested (n = 86) gave half‐maximal B‐lymphoma cell lysis (ED50) within a range of 10–50 pg/ml bscCD19xCD3, corresponding to sub‐picomolar concentrations of the bispecific antibody. Under identical experimental conditions, the anti‐CD20 monoclonal antibody rituximab had an at least 100,000‐fold lower in vitro efficacy. The extreme potency of bscCD19xCD3 was in sharp contrast to the relatively low affinity of the anti‐CD3 and anti‐CD19 single‐chain Fv portions in KD ranges of 10−7 and 10−9 M, respectively. Cell lysis by bscCD19xCD3 was predominantly mediated by the population of CD8/CD45RO‐positive T cells. Both immortalized CD4‐ and CD8‐positive human T‐cell clones were highly active effector cells as well. Cell lysis by bscCD19xCD3 was rapid and specific. The respective parental monoclonal antibodies inhibited cell lysis and CD19‐negative cells were not harmed by T cells in the presence of high amounts of bscCD19xCD3. The potent T‐cell stimulus IL‐2 could not markedly augment the activity of bscCD19xCD3‐stimulated T cells. In conclusion, bscCD19xCD3 could redirect unstimulated cytotoxic T cells against CD19‐positive cells in an unexpectedly potent, rapid and specific fashion. © 2002 Wiley‐Liss, Inc.
Cellular effects of CPT‐11 on colon carcinoma cells: Dependence on p53 and hMLH1 status
Authors: Magrini Roberta , Bhonde Mandar R. , Hanski Marie‐Luise , Notter Michael , Scherübl Hans , Boland C. Richard , Zeitz Martin , Hanski Christoph
Published: October 2002

Irinotecan (CPT‐11), a recently introduced component of a standard chemotherapy for colorectal cancer, induces in colon cancer cell lines in vitro cell cycle arrest and apoptosis. Since sporadic colon carcinomas exhibit in 50–60% mutations in the p53 gene and in 10–15% an MSI phenotype due in the great majority of the cases to hMLH1 inactivation, we investigated how these lesions influence the cellular effects of CPT‐11 by using colorectal carcinoma cell line HCT116 (which has the genotype p53+/+,hMLH1−) and 2 derivative cell lines with the genotypes p53+/+,hMLH1+ and p53−/−,hMLH1−. CPT‐11 treatment induced G2/M arrest in all 3 cell lines within 48 hr. In the p53+/+,hMLH1+ cell line, G2/M arrest was maintained for at least 12 days. There was little concomitant apoptosis, but this was enhanced when the hMLH1 protein was absent. This enhanced apoptosis was accompanied by a shorter duration of the G2/M arrest than in the hMLH1+ cell line. Partial abrogation of G2/M arrest by caffeine enhanced apoptosis in both hMLH1+ and hMLH1− cells. By contrast, in the p53−/− cell line, the G2/M arrest was terminated within 4 days. Termination of the G2/M arrest was accompanied by a high level of apoptosis detectable through poly(ADP‐ribose)polymerase (PARP) cleavage, DNA fragmentation and by the appearance of cells with a DNA content <2N. The triggering of G2/M arrest was accompanied in the 3 cell lines by a transient phosphorylation of cdc‐2, while the maintenance of the arrest in the p53+/+ cell lines was accompanied by the overexpression of p53 and p21 proteins and, consequently, by the inhibition of cdc‐2 kinase activity. These data indicate that: (i) CPT‐11 induces long‐term arrest in p53+/+ cells and a short‐term arrest followed by apoptosis in p53−/− cells; (ii) triggering of the arrest is p53 independent and is associated with a brief increase of phosphorylation of cdc‐2, while the p53‐dependent maintenance of G2/M arrest is associated with the inhibition of cdc‐2 kinase activity by p21; and (iii) lack of hMLH1 protein enhances CPT‐11‐induced apoptosis. These results may be useful for designing rational therapies dependent on the p53 and mismatch‐repair status in the tumor. © 2002 Wiley‐Liss, Inc.
TP53mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: Association with risk factors and tumor characteristics
Authors: Simão Tatiana A. , Ribeiro Fabiana S. , Amorim Lídia M. F. , Albano Rodolpho M. , Andrada‐Serpa Maria J. , Cardoso Lúis E. B. , Mendonça Gulnar A. S , de Moura‐Gallo Cláudia V.
Published: October 2002

Somatic mutations in theTP53gene are the most frequently observed genetic alterations in human malignancies, including breast cancer, which is one of the leading causes of death among women in Brazil. In our study, we determined the frequency and the pattern ofTP53mutations in malignant breast tumors from 120 patients living in Rio de Janeiro, Brazil.TP53mutations were found in 20% of the tumors, which contained a diversity of mutation types: missense (62.5%), nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at Cys242, which are directly involved in DNA binding and in zinc binding, respectively. A subgroup of 51 patients was analyzed with respect to the relation between the presence ofTP53mutations and classical risk factors and with tumor and patient characteristics. For this analysis, we used logistic regression and, in order to obtain more precise confidence intervals, they were recalculated using a bootstrap resampling technique. Our results demonstrate that these mutations are not statistically associated with the risk factors or the patients' characteristics. However, the presence ofTP53mutations is strongly associated with the aggressiveness of the tumors, measured by Elston classification (OR = 11.97 and 95% CI of 2.24–307.05). This finding is in agreement with previous studies, which report the presence ofTP53mutations in tumors with poor prognosis. This correlation between tumor aggressiveness andTP53mutations could be a crucial variable for the treatment and prognosis of breast cancer. © 2002 Wiley‐Liss, Inc.
Affect expression in prenatally psychotropic exposed and nonexposed mother–infant dyads
Authors: Reebye Pratibha N. , Morison Sara J. , Panikkar Hira , Misri Shaila , Grunau Ruth E.
Published: October 2002

This prospective study examined infant, maternal, and dyadic affective profiles at three months postpartum in infant–mother dyads that were exposed to psychotropic medications in utero compared with nonexposed control dyads. Control dyads of nondepressed mothers and their infants showed many similarities in affect expression with mother–infant dyads who were exposed to selective serotonin reuptake inhibitors (SSRIs) alone for treatment of maternal depression. In contrast, mothers who received SSRIs and Rivotril (Benzodiazepine derivative) for treatment of depression and anxiety expressed both positive and negative affect towards their infants. Clinical implications regarding use of psychotropic medications such as SSRIs alone or in combination with other drugs for treatment of maternal anxiety and depression during pregnancy are discussed. Clinicians should be aware of the possible differential response in maternal–infant interaction in a mixed diagnosis group (i.e., depression and anxiety) regarding infant temperament, possibly suggesting latent behavioral teratogenicity with psychotropics. ©2002 Michigan Association for Infant Mental Health.
Mineral deficiency and the use of the FETAX bioassay to study environmental teratogens
Authors: Garber Eric A. E.
Published: October 2002

The Frog Embryo Teratogenesis Assay: Xenopus (FETAX) bioassay has been employed extensively to screen compounds for teratogenic activity. Recent laboratory studies have indicated that low potassium concentrations retard Xenopus laevis development. The effects of varying concentrations of minerals on Xenopus laevis embryo length and development were examined to determine the utility of the FETAX bioassay in the study of environmental teratogens. Water samples collected from 18 wetlands in Minnesota and North Dakota correlated with low mineral levels, causing delayed embryonic development in the FETAX bioassay. When the concentration of sodium or potassium was <5 ppm, Xenopus laevis development was delayed. As a result, it was difficult to assess teratogenic activity after 96 h of incubation. Furthermore, the length of the embryos—an indication of development—paralleled changes in mineral composition. Comparisons between different wetlands based on changes in one specific mineral were not possible due to a synergism between various minerals. If the concentration of sodium and/or potassium was <5 ppm but ≥2 ppm, extension of the FETAX bioassay to 120 h allowed organogenesis to proceed through stage 46, as required for scoring in accordance with ASTM guidelines for the FETAX bioassay. In those cases in which the concentration of sodium and/or potassium were <2 ppm, the embryos could not develop to stage 46 within 120 h and the FETAX bioassay was not suitable for detecting teratogenic activity. Published in 2002 by John Wiley & Sons, Ltd.
Assessment of genome damage in a population of Croatian workers employed in pesticide production by chromosomal aberration analysis, micronucleus assay and Comet assay
Authors: Garaj‐Vrhovac Vera , Zeljezic Davor
Published: October 2002

The widespread use of pesticides suggests that the evaluation of their genotoxicity should be extended using the different assays available. In the present study we used two standard cytogenetic methods (chromosomal aberration analysis and micronucleus assay) and the Comet assay as a relatively new and powerful technique. The study included 10 workers occupationally exposed to a complex mixture of pesticides (atrazine, alachlor, cyanazine, 2,4‐dichlorophenoxyacetic acid, malathion) during their production and 20 control subjects with no history of exposure to any physical or chemical agents. For the chromosomal aberration analysis, whole blood was cultivated for 48 h, whereas for the micronucleus assay, whole blood was cultivated for 72 h. For the comet assay whole blood was embedded in agarose on a microscope slide, lysed with detergent, denaturated and subjected to alkaline electrophoresis. Damage to DNA was evaluated by measuring tail length and calculating the tail moment. A significantly increased number of chromatid and chromosome breaks, as well as the presence of dicentric chromosomes and chromatid exchanges in exposed subjects compared with control subjects (P < 0.05), was found. There was also a statistically significant difference in frequency and distribution of micronuclei between the two groups examined. In the exposed subjects the Comet assay showed a statistically significant (P < 0.001) increase in DNA migration. Results suggest that long‐term occupational exposure to pesticides could cause genome damage in somatic cells and therefore may represent a potential hazard to human health. Copyright © 2002 John Wiley & Sons, Ltd.
Mechanisms of magnesium‐stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants
Authors: Zreiqat H. , Howlett C. R. , Zannettino A. , Evans P. , Schulze‐Tanzil G. , Knabe C. , Shakibaei M.
Published: October 2002

Poor cell adhesion to orthopaedic and dental implants may result in implant failure. Cellular adhesion to biomaterial surfaces primarily is mediated by integrins, which act as signal transduction and adhesion proteins. Because integrin function depends on divalent cations, we investigated the effect of magnesium ions modified bioceramic substrata (Al2O3‐Mg2+) on human bone‐derived cell (HBDC) adhesion, integrin expression, and activation of intracellular signalling molecules. Immunohistochemistry, flow cytometry, cell adhesion, cell adhesion blocking, and Western blotting assays were used. Our findings demonstrated that adhesion of HBDC to Al2O3‐Mg2+ was increased compared to on the Mg2+‐free Al2O3. Furthermore, HBDC adhesion decreased significantly when the fibronectin receptor α5β1‐ and β1‐integrins were blocked by functional blocking antibodies. HBDC grown on the Mg2+‐modified bioceramic expressed significantly enhanced levels of β1‐, α5β1‐, and α3β1‐integrins receptors compared to those grown on the native unmodified Al2O3. Tyrosine phosphorylation of intracellular integrin‐dependent signalling proteins as well as the expression of key signalling protein Shc isoforms (p46, p52, p66), focal adhesion kinase, and extracellular matrix protein collagen type I were significantly enhanced when HBDC were grown on Al2O3‐Mg2+ compared to the native Al2O3. We conclude that cell adhesion to biomaterial surfaces is probably mediated by α5β1‐ and β1‐integrin. Cation‐promoted cell adhesion depends on 5β1‐ and β1‐integrins associated signal transduction pathways involving the key signalling protein Shc and results also in enhanced gene expression of extracellular matrix proteins. Therefore, Mg2+ supplementation of bioceramic substrata may be a promising way to improve integration of implants in orthopaedic and dental surgery. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 175–184, 2002
New acrylic bone cements conjugated to vitamin E: Curing parameters, properties, and biocompatibility
Authors: Méndez J.A. , Aguilar M.R. , Abraham G.A. , Vázquez B. , Dalby M. , Di Silvio L. , San Román J.
Published: October 2002

Acrylic bone cement formulations with antioxidant character were prepared by incorporation of a methacrylic monomer derived from vitamin E (MVE). Increasing concentrations of this monomer provided decreasing peak temperature values, ranging from 62 to 36°C, and increasing setting time with values between 17 and 25 min. Mechanical properties were evaluated by compression and tension tests. Compressive strength of the new formulations were superior to 70 MPa in all cases. The cement containing 25 wt % MVE, however, showed a significant decrease in tensile properties. Biocompatibility of the new formulations was studied in vitro. The analysis of the effect of leachables from cements into the media showed continued cell proliferation and cell viability with a significant increase for the cement containing 15 wt % MVE. This formulation also showed a significant increase in cellular proliferation over a period of 7 days as indicated by the Alamar Blue test. The cells were able to differentiate and express phenotypical markers in presence of all materials. A significant increase in alkaline phosphatase activity was observed on the cements prepared in presence of 15–25 wt % MVE compared with PMMA. Morphological assessment showed that the human osteoblast (HOB) cells were able to adhere, retain their morphology, and proliferate on all the cements. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 299–307, 2002
Web‐Based Contracts: You Could Be Burned!
Authors: Durtschi Cindy , Hillison William , Pacini Carl
Published: October 2002

The Internet is the new Wild West for companies venturing into Web‐based commerce. Someone can consent

to complex electronic agreements with a simple mouse click. But what must you know so you don't get

burned? © 2002 Wiley Periodicals, Inc.
Differential regulation of Cbfa1/Runx2 and osteocalcin gene expression by vitamin‐D3, dexamethasone, and local growth factors in primary human osteoblasts
Authors: Viereck Volker , Siggelkow Heide , Tauber Simone , Raddatz Dirk , Schutze Norbert , Hüfner Michael
Published: October 2002

Core binding factor alpha 1 (Cbfa1) is an osteoblast‐specific transcription factor essential to develop a mature osteoblast phenotype. However, its exact role in the signaling of various osteotropic‐differentiating agents is still unclear. In this study, we assessed the effects of 1,25‐(OH)2‐D3 (D3), ascorbic acid, bone morphogenetic protein‐2 (BMP‐2), dexamethasone (Dex), and transforming growth factor‐β (TGF‐β) on Cbfa1 and osteocalcin (OCN) mRNA steady state levels (by semiquantitative RT‐PCR) in an in vitro model of osteoblast differentiation. TGF‐β increased Cbfa1 mRNA levels in normal primary human osteoblasts (pHOB) by 2.6‐fold in a time‐dependent fashion with maximum effect on day 28 (P < 0.001). Similarly, the glucocorticoid Dex enhanced Cbfa1 gene expression by pHOB in a time‐dependent fashion by up to 4.6‐fold (P < 0.001). In contrast, Dex inhibited OCN gene expression levels by 68% (P < 0.01). Treatment with BMP‐2 resulted in an earlier enhancement of Cbfa1 and led to a 4.2‐fold increase with a maximum on day 21 (P < 0.001). Ascorbic acid did not modulate Cbfa1 and OCN gene expression. The effect of vitamin D (D3) on Cbfa1 mRNA expression was influenced by the duration of treatment, being inhibitory after 1 h and having a stimulatory effect after 48 h. Time course experiments indicated a stimulatory effect of D3 on Cbfa1 mRNA levels (by 2.5‐fold after 48 h; P < 0.01). Analysis of the late cellular differentiation marker osteocalcin revealed that D3 increased OCN gene expression by 14‐fold (P < 0.001). In conclusion, in normal primary human osteoblasts, the rapid and pronounced increase of OCN after treatment with D3 seems not to be mediated by Cbfa1. These data imply that Cbfa1 gene expression is differentially regulated by various osteoblastic differentiating agents and is dependent on the stage of maturation. J. Cell. Biochem. 86: 348–356, 2002. © 2002 Wiley‐Liss, Inc.
Linear scaling local correlation approach for solving the coupled cluster equations of large systems
Authors: Li Shuhua , Ma Jing , Jiang Yuansheng
Published: October 2002

A linear scaling local correlation approach is proposed for approximately solving the coupled cluster doubles (CCD) equations of large systems in a basis of orthogonal localized molecular orbitals (LMOs). By restricting double excitations from spatially close occupied LMOs into their associated virtual LMOs, the number of significant excitation amplitudes scales only linearly with molecular size in large molecules. Significant amplitudes are obtained to a very good approximation by solving the CCD equations of various subsystems, each of which is made up of a cluster associated with the orbital indices of a subset of significant amplitudes and the local environmental domain of the cluster. The combined effect of these two approximations leads to a linear scaling algorithm for large systems. By using typical thresholds, which are designed to target an energy accuracy, our numerical calculations for a wide range of molecules using the 6‐31G or 6‐31G* basis set demonstrate that the present local correlation approach recovers more than 98.5% of the conventional CCD correlation energy. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 237–244, 2002
Structure and dynamics of liquid water with different long‐range interaction truncation and temperature control methods in molecular dynamics simulations
Authors: Mark Pekka , Nilsson Lennart
Published: October 2002

We have used molecular dynamics simulations to study the physical properties of modified TIP3P water model included in the CHARMM program, using four different methods—the Ewald summation technique, and three different spherical truncation methods—for the treatment of the long‐range interactions. Both the structure and dynamics of the liquid water model were affected by the methods used to truncate the long‐range interactions. For some of the methods artificial structuring of the model liquid was observed around the cutoff radius. The model liquid properties were also affected by the commonly applied temperature control methods. Four different methods for controlling the temperature of the system were studied, and the effects of these methods on the bulk properties for liquid water were analyzed. The system size was also found to change the dynamics of the model liquid water. Two control simulations with the SPC/E water model were carried out. The self‐diffusion coefficient (D), the radial distribution function (gOO), the distance dependent Kirkwood G‐factor [Gk(r)] and the intermolecular potential energy (Epot) were determined from the different trajectories and compared with the experimental data. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1211–1219, 2002
Accelerated Poisson–Boltzmann calculations for static and dynamic systems
Authors: Luo Ray , David Laurent , Gilson Michael K.
Published: October 2002

We report here an efficient implementation of the finite difference Poisson–Boltzmann solvent model based on the Modified Incomplete Cholsky Conjugate Gradient algorithm, which gives rather impressive performance for both static and dynamic systems. This is achieved by implementing the algorithm with Eisenstat's two optimizations, utilizing the electrostatic update in simulations, and applying prudent approximations, including: relaxing the convergence criterion, not updating Poisson–Boltzmann‐related forces every step, and using electrostatic focusing. It is also possible to markedly accelerate the supporting routines that are used to set up the calculations and to obtain energies and forces. The resulting finite difference Poisson–Boltzmann method delivers efficiency comparable to the distance‐dependent dielectric model for a system tested, HIV Protease, making it a strong candidate for solution‐phase molecular dynamics simulations. Further, the finite difference method includes all intrasolute electrostatic interactions, whereas the distance dependent dielectric calculations use a 15‐Å cutoff. The speed of our numerical finite difference method is comparable to that of the pair‐wise Generalized Born approximation to the Poisson–Boltzmann method. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1244–1253, 2002
Derivation of class II force fields. VIII. Derivation of a general quantum mechanical force field for organic compounds
Authors: Ewig Carl S. , Berry Rajiv , Dinur Uri , Hill Jörg‐Rüdiger , Hwang Ming‐Jing , Li Haiying , Liang Chris , Maple Jon , Peng Zhengwei , Stockfisch Thomas P. , Thacher Thomas S. , Yan Lisa , Ni Xiangshan , Hagler Arnold T.
Published: October 2002

A class II valence force field covering a broad range of organic molecules has been derived employing ab initio quantum mechanical “observables.” The procedure includes selecting representative molecules and molecular structures, and systematically sampling their energy surfaces as described by energies and energy first and second derivatives with respect to molecular deformations. In this article the procedure for fitting the force field parameters to these energies and energy derivatives is briefly reviewed. The application of the methodology to the derivation of a class II quantum mechanical force field (QMFF) for 32 organic functional groups is then described. A training set of 400 molecules spanning the 32 functional groups was used to parameterize the force field. The molecular families comprising the functional groups and, within each family, the torsional angles used to sample different conformers, are described. The number of stationary points (equilibria and transition states) for these molecules is given for each functional group. This set contains 1324 stationary structures, with 718 minimum energy structures and 606 transition states. The quality of the fit to the quantum data is gauged based on the deviations between the ab initio and force field energies and energy derivatives. The accuracy with which the QMFF reproduces the ab initio molecular bond lengths, bond angles, torsional angles, vibrational frequencies, and conformational energies is then given for each functional group. Consistently good accuracy is found for these computed properties for the various types of molecules. This demonstrates that the methodology is broadly applicable for the derivation of force field parameters across widely differing types of molecular structures. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1782–1800, 2001
Diagnosing complicated grief: A closer look
Authors: Enright Brian P. , Marwit Samuel J.
Published: October 2002

Over the past decade, a number of researchers have proposed a separate DSM category for complicated grief. Recently, there have been attempts to determine empirically the number and nature of variables comprising the complicated‐grief syndrome. The present research addresses one such procedure for defining these variables. Combining a past methodology that demonstrated the relative utility of one classification of complicated grief (Worden, 1991) with dimensional concepts derived from other classifications, the present research concludes that a relatively small number of variables account for the concept. These findings are discussed not only in terms of previous research on Worden's categorization and more recent classifications, but, more importantly, in terms of the more global theoretical and methodological issues surrounding the definition(s) of complicated grief. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 747‐757, 2002.
Remission, recovery, relapse, and recurrence in eating disorders: Conceptualization and illustration of a validation strategy
Authors: Kordy Hans , Krämer Beatrice , Palmer Robert L. , Papezova Hana , Pellet Jacques , Richard Matthias , Treasure Janet , COST Action B6
Published: October 2002

In a consensus‐building process a group of experts from 19 European countries (COST Action B6) adapted the terms partial and full remission, relapse, recovery, and recurrence according to principles described by Frank et al. for depression. The empirical validity of the operationalizations was illustrated by longitudinal data on the post treatment course of 233 anorectic and 422 bulimic patients (diagnosed according to DSM‐IIIR) from the German Project TR‐EAT. These data were collected 2.5 years after admission using the Longitudinal Interval Follow‐up Evaluation (LIFE) and statistically explored by survival‐analysis. It was demonstrated that these consensus definitions measure what they intend to measure. They open a longitudinal perspective in that one can learn not only whether, but also when and with what probability patients change for the better or worse. Data suggest that persistence of symptom improvement has different implications for anorexia and bulimia nervosa. For example, relapse prevention would be most beneficial for bulimic patients for about 4 months after key symptoms remit, while this would be of less importance for anorexic patients. It is discussed whether and how this longitudinal approach can contribute to an empirically based rationale for targeted and individualized treatment. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 833–846, 2002