bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomantle formation and artifact translocation in upland sandy soils: An example from the Holly Springs National Forest, north‐central Mississippi, U.S.A.
Authors: Peacock Evan , Fant David W.
Published: August 2002

Test excavations at prehistoric site 22MR539 in the North Central Hills uplands of Mississippi have provided evidence of the effects of bioturbation on artifacts within the soil. Artifact distribution and size data are compared to soil particle size and organic content to determine the soil developmental pathway. Progressive soil formation factors have formed a biomantle over a currently forming artifact stone line, while regressive factors have moved artifacts to a depth of more than 50 cm below surface over approximately 2000 years. The single‐component, short‐term nature of 22MR539 and many similar sites recorded in the area provide an ideal situation to further explore biological and mechanical factors in site formation in an upland setting. © 2002 John Wiley & Sons, Inc.
Structural and petrological constraints on the tectono‐metamorphic evolution of the Massa Unit (Alpi Apuane, NW Tuscany, Italy)
Authors: Molli Giancarlo , Giorgetti Giovanna , Meccheri Marco
Published: August 2002

A study of the metamorphic and tectonic evolution of the Massa Unit in the Alpi Apuane Metamorphic Complex shows that this unit suffered relatively high‐pressure conditions (peak higher than 0.8 GPa) and was exhumed during a multiphase history. The first stage of exhumation occurred during Tertiary continental collision between Adria and Sardinia/Corsica and was associated with the thrusting of the more deeply buried chloritoid + kyanite‐bearing Massa Unit on top of the less deeply buried chloritoid + pyrophyllite‐bearing Apuane Unit. The subsequent stages of exhumation were shared by the two metamorphic units and were coeval with the beginning of crustal extension related to the opening of the Tyrrhenian Sea. Copyright © 2000 John Wiley & Sons, Ltd.
Origin of quartz geodes from Laño and Tubilla del Agua sections (middle–upper Campanian, Basque‐Cantabrian Basin, northern Spain): isotopic differences during diagenetic processes
Authors: Gómez‐Alday Juan J. , García‐Garmilla Francisco , Elorza Javier
Published: August 2002

Quartz geodes and nodular chert have been found within middle–upper Campanian carbonate sediments from the Laño and Tubilla del Agua sections of the Basque‐Cantabrian Basin, northern Spain. The morphology of geodes together with the presence of anhydrite laths included in megaquartz crystals and spherulitic fibrous quartz (quartzine‐lutecite), suggest an origin from previous anhydrite nodules. The anhydrite nodules at Laño were produced by the percolation of marine brines, during a period corresponding to a sedimentary gap, with δ34S and δ18O mean values of 18.8‰ and 13.6‰ respectively, consistent with Upper Cretaceous seawater sulphate values. Higher δ34S and δ18O mean values of 21.2‰ and 21.8‰ recorded in the Tubilla del Agua section are interpreted as being due to a partial bacterial sulphate reduction process in a more restricted marine environment. The idea that sulphates may have originated from the leaching of previously deposited Keuper sulphate evaporites with subsequent precipitation as anhydrite, is rejected because the δ34S, δ18O and 87Sr/86Sr values of anhydrite laths observed at both the Tubilla del Agua and Laño sections suggest an origin from younger marine brines. Later calcite replacement and precipitation of geode‐filling calcite is recorded in both sections, with δ13C and δ18O values indicating the participation of meteoric waters. Synsedimentary activity of the Peñacerrada diapir, which lies close to the Laño section, played a significant role in the local shallowing of the basin and the formation of quartz geodes. In contrast, eustatic shallowing of the inner marine series of the Tubilla del Agua section led to the generation of morphologically similar quartz geodes. Copyright © 2002 John Wiley & Sons, Ltd.
Electrophysiological characterization of retinal Müller glial cells from mouse during postnatal development: Comparison with rabbit cells
Authors: Pannicke Thomas , Bringmann Andreas , Reichenbach Andreas
Published: August 2002

The electrophysiology of murine Müller cells, and of their precursors, during postnatal development was investigated by using the whole‐cell patch‐clamp technique. Membrane potential, membrane capacitance, and expression of voltage‐gated Na+ currents increased during the first 3 postnatal weeks. During the same period, the membrane resistance decreased due to an upregulation of both inward and outward K+ currents. Glutamate transporter‐mediated currents increased during the first postnatal weeks, as well. In Müller (precursor) cells from rabbits, these transporter currents already achieved adult levels at postnatal day 6, the earliest stage studied. Together with the developmental time course of K+ currents, this indicates a delay in the maturation of murine Müller cells, as compared with cells from rabbit. GLIA 38:268–272, 2002. © 2002 Wiley‐Liss, Inc.
Markers for the functional availability of cobalamin/folate and their association with neuropsychiatric symptoms in the elderly
Authors: Hultberg Björn , Isaksson Anders , Nilsson Karin , Gustafson Lars
Published: August 2002

Cobalamin/folate deficiency is common in elderly subjects and may lead to psychiatric symptoms, but even more often it increases the severity of other organic and non‐organic mental diseases. This paper reviews the literature relevant for markers of cobalamin/folate status and their relation to neuropsychiatric symptoms in the elderly. Plasma homocysteine, a marker of cobalamin/folate status, is frequently increased in psychogeriatric patients. Among markers of cobalamin/folate status, plasma homocysteine shows the best association with neuropsychiatric dysfunction. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis and bioactivities of 1,3,2‐benzodiazaphosphorin‐2‐carboxamide 2‐oxides containing α‐aminophosphonate groups
Authors: Huang Junmin , Chen Ruyu
Published: August 2002

In order to search for novel antitumor and antiviral agents with high activity and low toxicity, a series of 1‐ethoxycarbonylmethyl‐3‐ethyl‐1,2,3,4‐tetrahydro‐4‐oxo‐1,3,2‐benzodiazaphosphorin‐2‐carboxamide 2‐oxides containing α‐aminophosphonate groups have been designed and synthesized by a convenient one‐pot procedure in good yields. The structures of products were confirmed by 1H NMR, 31P NMR, IR spectra, and elemental analyses. The bioassay results showed that some of them possess excellent anti–tobacco mosaic virus activities and exhibit higher inhibitory effects compared with that of the contrast drug 2,4‐dioxyhexahydro‐1,3,5‐triazine. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:97–101, 2001
Documenting the Landscape: Results of a National Study on Academic and Student Affairs Collaborations
Authors: Kezar Adrianna
Published: August 2002

Colleges and universities have different reasons for collaborative efforts, different problems with them, and different solutions.
How valuable are student exchange programs?
Authors: Sowa Patience A.
Published: August 2002

Student exchange programs have numerous merits, including promoting students' intellectual development and providing economic resources for the U.S. economy. But such programs are not without their liabilities.
Twenty years of health care economic analysis in Spain: are we doing well?
Authors: García‐Altés Anna
Published: August 2002

The rising demand for health care, together with the scarce available resources, has increased the use of economic analysis as a support tool for policy making. The objective of this study was to make a description of economic evaluation studies carried out in Spain and published during the last 20 years, and to assess their quality.

A systematic bibliographic search was made in the main biomedical databases. Full economic evaluation studies made in Spain comparing two or more health care alternatives were included. Statistical analyses included a descriptive analysis, the assessment of the association between pairs of variables, and a homogeneity analysis.

A total of 87 studies were included in the review. According to the methodology, the technique most frequently used was cost‐effectiveness analysis. In most cases, some weaknesses could be pointed out: absence of any objective directly linked to the decision‐making process, a non‐explicit perspective, no inclusion of indirect costs, or clinical and economical data not concurrently collected.

A continuing challenge for health care economic analysis in Spain is to follow methodological guidelines and reporting conventions, to improve the dissemination of research, as well as to use more sophisticated economic analysis techniques, and to publish in international journals. Copyright © 2001 John Wiley & Sons, Ltd.
The desirability of a condition versus the well being and worth of a person
Authors: Nord Erik
Published: August 2002

The desirability of a condition to people who are not in it themselves is only moderately correlated to the experienced well being of people with the condition and hardly correlated at all to the worth of those people. A single score for a health state, of the kind used in QALY calculations, cannot express all these three types of value. The history and current practice of health economics is highly problematic in this respect. Copyright © 2001 John Wiley & Sons, Ltd.
Apoptosis and its clinical impact
Authors: Gastman Brian R.
Published: August 2002

Background

Apoptosis or programmed cell death is an orderly cascade that can be regulated and ultimately results in the demise of the cell. Induction of apoptosis can occur by various chemical and biologic agents. Initiation of apoptosis leads to activation of effector molecules particularly caspases. These proteases cleave distinct protein substrates, resulting in the morphologic changes seen in apoptosis. This form of cell death is involved in almost every physiologic and pathogenic process in the body. For this reason the ability to control apoptosis has important therapeutic ramifications.

Results

This article reviews the history of the investigation of apoptosis and summarizes the most important pathways and regulatory molecules involved in this process. The major regulators of apoptosis, including the Bcl‐2, caspase, and inhibitor of apoptosis families, are examined. The two major apoptotic pathways, including the extrinsic/cell surface death receptor and the intrinsic/mitochondrial pathways, are discussed. A major emphasis is given to examining the relationship between apoptosis and certain disease processes. This review specifically focuses on the importance of apoptosis research in the development of new methods of management of cancer with an emphasis in head and neck oncology.

Conclusions

Apoptosis is a rapidly growing field. The understanding of the mechanisms and effector molecules controlling this form of cell death is evolving. On the basis of increasing knowledge of how programmed cell death is regulated and the improvements in designing and developing gene therapies and chemicals that are more accurate in targeting specific molecules, the control of apoptosis will become more important in the clinical setting. This possibility will open the door for new therapeutic endeavors in many areas of medicine and specifically in the area of oncology. © 2001 John Wiley & Sons, Inc. Head Neck 23: 409–425, 2001.
Surgical treatment of cervical node metastases from squamous carcinoma of the upper aerodigestive tract: Evaluation of the evidence for modifications of neck dissection
Authors: Buckley J. Graham , Feber Trish
Published: August 2002

Background

This review article examines the role of the different types of neck dissection in the treatment of squamous carcinoma metastases to the cervical nodes.

Methods

A critical evaluation of the literature on the pathologic basis, oncologic effectiveness, and functional outcome of neck dissection.

Results

Pathologic data show preferential metastasis to different lymph node levels, in N0− and N+‐staged disease, depending on the primary tumor site. Comparative studies on control of regional metastases suggest that modified radical is no less effective than radical neck dissection, but there is insufficient data to draw firm conclusions on the role of selective neck dissection. Selective and modified radical dissections result in less shoulder disability than radical neck dissection.

Conclusions

Modified radical neck dissection is supported by pathologic and clinical evidence in N1‐ and 2‐staged disease. There may be a role for selective dissection, but there is a need for more information on oncologic outcome. Prospective multicenter systematic data collection on the outcome of neck dissection is a pragmatic alternative to a trial. © 2001 John Wiley & Sons, Inc. Head Neck 23: 907–915, 2001.
A methodology for systemic‐structural analysis and design of manual‐based manufacturing operations
Authors: Bedny Gregory , Karwowski Waldemar , Kwon Young‐Guk
Published: August 2002

The main objective of this study was to develop a method for systemic‐structural analysis and design of manufacturing assembly operations based on the activity theory. The “activity” was defined as behavior distinctively specific to workers, associated with mobilizations and realization of conscious manufacturing goals. The fundamental units of analysis of activity are actions that are both motor and mental. Activity is considered as a complicated structure of actions that are logically ordered in space and time. Each action is comprised of different operations. The building blocks of motor actions are motions. The building blocks of cognitive actions are mental operations. Activity integrates not merely cognitive and behavioral components, but the energy components as well. The proposed methodology is illustrated using an example of two manufacturing assembly operations. © 2001 John Wiley and Sons, Inc.
Integrating learning and work: Problems and prospects
Authors: Ellström Per‐Erik
Published: August 2002

In spite of a widespread belief in the importance of integrating learning and work, little is known about
the conditions that promote such an integration. In order to both clarify the concept of learning and see how
to integrate learning and work, this article distinguishes between two major modes of learning: adaptive and
developmental learning, which the author breaks down into four levels. Using these conceptualizations as a
starting point, the article focuses on identifying and analyzing a number of factors that are assumed to be
critical for facilitating or constraining an integration of learning and work.
The Impact of Same‐Sex LMX Dyads on Performance Evaluations
Authors: Varma Arup , Stroh Linda K.
Published: August 2002

Numerous studies have found that supervisors rate women lower than men for similar levels of performance,
suggesting that for female employees, performance alone may not be able to guarantee fair ratings. What is not
clear is whether this disparity is a function of the gender composition of the supervisor–subordinate dyad
or simply a case of male supervisor rating behavior. Based on data from supervisor–subordinate dyads in four
organizations, we found that after controlling for performance, both male and female supervisors
exhibit a positive bias toward subordinates of the same sex and rate members of the same gender higher. ©
2001 John Wiley & Sons, Inc.
360 Feedback from Another Angle
Authors: Bracken David W. , Timmreck Carol W. , Fleenor John W. , Summers Lynn
Published: August 2002

How do you know if a 360 process has been implemented successfully? What are the factors that influence its success? How can those factors be controlled by those responsible for its implementation? Despite its popularity, there has been little effort to build a comprehensive model that addresses these fundamental questions about 360 feedback. In a quest for such a model, we identify a host of key factors organized according to whether they exert their influence proximally or distally. We discuss how each factor contributes to successful implementation. After identifying how design features of a 360 process affect these key factors, we recommend how to enhance the probability of implementing 360 feedback successfully and sustaining the process over time. © 2001 John Wiley & Sons, Inc.
Heat transfer characteristics in a pulsating fluidized bed in relation to bubble characteristics
Authors: Nishimura Akira , Deguchi Seiichi , Matsuda Hitoki , Hasatani Masanobu , Mujumdar Arun S.
Published: August 2002

A pulsating fluidized bed is operated with two sequential durations designated as an on‐period with injecting fluidization gas and an off‐period without it. The heat transfer coefficient between a vertically immersed heater and bed in a pulsating fluidized bed is measured under various pulse cycles and fluidized particles. The obtained results are compared with those in a normal fluidized bed with continuous fluidization air injection. The relationship between heat transfer coefficients and bubble characteristics, evaluated using a digital video camera, has also been investigated. For certain fluidized particles and operating pulse cycles, the fluidization of particles and the increment of heat transfer coefficients can be obtained under a mean air velocity based on a pulse cycle duration smaller than the minimum fluidization air velocity in a normal fluidized bed. Under the pulse cycles where a static bed through the whole bed is formed in the off‐period duration, the improved heat transfer rate over that in a normal fluidized bed can be measured. This may be attributed to large bubble formation. As heat transfer in the pulsating fluidized bed is obstructed with increasing time to keep a static bed due to the excessive off‐period duration, it is indicated that there is an optimum off‐period duration based on the heat transfer rate. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(4): 307–319, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10038
Psychological profile of abstinent recreational Ecstasy (MDMA) users and significance of concomitant cannabis use
Authors: Daumann Joerg , Pelz Susanna , Becker Stefanie , Tuchtenhagen Frank , Gouzoulis‐Mayfrank Euphrosyne
Published: August 2002

The popular recreational drug Ecstasy (3,4‐methylenedioxymethamphetamine, or MDMA, and related congeners) is neurotoxic upon central serotonergic systems in animal studies. So far, the most convincing evidence for neurotoxicity‐related functional deficits in humans derives from neurocognitive studies demonstrating dose‐related memory problems in Ecstasy users. The aim of the current investigation was to study the relationship between the psychological profile of recreational Ecstasy users and the patterns of their drug use. Twenty‐eight abstinent recreational Ecstasy users with concomitant use of cannabis only and two equally sized, matched groups of cannabis users and non‐users were administered standardized self‐rating scales for the assessment of psychological problems which are thought to be related to central serotonergic function. Ecstasy users had elevated scores on subscales measuring impulsiveness, anxiety, sensation seeking, somatic complaints, obsessive‐compulsive behavior and psychoticism. Higher scores were associated with both heavier Ecstasy and heavier cannabis use. After controlling for cannabis use, most group differences in psychometric scores no longer achieved statistical significance. The present data are in line with other reports demonstrating a broad range of psychological problems in Ecstasy users. However, the concomitant use of other drugs, specifically cannabis, seems to be crucial in this respect. Therefore, compared with cognitive deficits, psychological problems appear to be less suitable functional indices of Ecstasy‐related neurotoxic damage of central serotonergic systems in humans. Copyright © 2001 John Wiley & Sons, Ltd.
Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies
Authors: Liechti Matthias E. , Vollenweider Franz X.
Published: August 2002

In preclinical studies, 3,4‐methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) has been shown to release serotonin (5‐HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5‐HT2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double‐blind placebo‐controlled within‐subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self‐confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA‐induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA‐induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier‐mediated 5‐HT release, while the more stimulant‐like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D2 receptor stimulation. The mild hallucinogen‐like perceptual effects of MDMA appear to be due to serotonergic 5‐HT2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd.
Scaling aspects of river flow routing
Authors: Arora Vivek , Seglenieks Frank , Kouwen Nick , Soulis Eric
Published: August 2002

Scaling aspects of river flow routing are studied by comparing two flow routing schemes, one designed for use in coupled general circulation models (GCMs) and operated at large spatial scales (∼350 km), and the other designed for use in typical hydrological applications at small spatial scales (∼25 km). The same runoff data are used as input into the two routing schemes, and comparisons are made between mean annual, mean monthly and daily streamflow simulated at four locations within the Mackenzie River Basin. The results suggest that for the purpose of realistically modelling monthly streamflow at the mouth of the rivers in GCMs, flow routing at large spatial scales gives similar results. However, the amplitude of the annual streamflow cycle is slightly but characteristically larger, when routing is performed at large spatial scales. Flow routing at large spatial scales also results in overestimation of high flows, while low flows are underestimated. Copyright © 2001 John Wiley & Sons, Ltd.
Reedbed evapotranspiration rates in England
Authors: Fermor P. M. , Hedges P. D. , Gilbert J. C. , Gowing D. J. G.
Published: August 2002

Measurements of evapotranspiration from contrasting stands of Phragmites australis [ET(Reed)] were obtained over several years at three sites within England between 1994 and 1998. A comparison with published ET(Reed) values showed the UK rates to be considerably lower than those measured in continental Europe. From the ET(Reed) data monthly crop coefficients [Kc(Reed)] have been developed, which when used with Reference Crop Evapotranspiration will enable reedbed water use to be determined. Due to the differences in study site characteristics, values for Kc varied widely, and it was not considered appropriate to combine results to produce a single set of monthly mean values. However, suggestions are made regarding the application of the Kc(Reed) values to wetland design. Copyright © 2001 John Wiley & Sons, Ltd.
Refinement of predictive reaeration equations for a typical Indian river
Authors: Jha Ramakar , Ojha C. S. P. , Bhatia K. K. S.
Published: August 2002

Dissolved oxygen mass balance has been computed for different reaches of River Kali in western Uttar Pradesh (India) to obtain the reaeration coefficient (K2). A total of 270 field data sets have been collected during the period from March 1999 to February 2000. Eleven most popular predictive equations, used for reaeration prediction and utilizing mean stream velocity, bed slope, flow depth, friction velocity and Froude number, have been tested for their applicability in the River Kali using data generated during field survey. The K2 values computed from these predictive equations have been compared with the K2 values observed from dissolved oxygen balance measurements in the field. The performance of predictive equations have been evaluated using error estimation, namely standard error (SE), normal mean error (NME), mean multiplicative error (MME) and correlation statistics. The equations developed by Smoot and by Cadwallader and McDonnell showed comparatively better results. Moreover, a refined predictive equation has been developed using a least‐squares algorithm for the River Kali that minimizes error estimates and improves correlation between observed and computed reaeration coefficients. Copyright © 2001 John Wiley & Sons, Ltd.
Hydrological impacts of forest conversion to agriculture in a large river basin in northeast Thailand
Authors: Wilk J. , Andersson L. , Plermkamon V.
Published: August 2002

Small‐scale experiments have demonstrated that forest clearance leads to an increase in water yield, but it is unclear if this result holds for larger river basins (>1000 km2). No widespread changes in rainfall totals and patterns were found in the 12 100 km2 Nam Pong catchment in northeast Thailand between 1957 and 1995, despite a reduction in the area classified as forest from 80% to 27% in the last three decades. Neither were any detectable changes found in any other water balance terms nor in the dynamics of the recession at the end of the rainy season. When a hydrological model calibrated against data from the period before the deforestation was applied for the last years of the study period (1987–1995), runoff generation was however underestimated by approximately 15%, indicating increased runoff generation after the deforestation. However, this was mainly due to the hydrological response during one single year in the first period, when the Q/P ratio was very low. When excluding this year, neither analysis based on the hydrological model could reveal any significant change of the water balance due to the deforestation. More detailed land‐use analysis revealed that shade trees were left on agricultural plots as well as a number of abandoned areas where secondary growth can be expected, which is believed to account for the results. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of rainfall and salt‐wedge movement on phytoplankton succession in the Swan–Canning Estuary, Western Australia
Authors: Twomey L. , John J.
Published: August 2002

Annual data sets, from 1980–81 and 1994–95, provide evidence that inter‐annual differences in the seasonal succession of phytoplankton in the Swan River Estuary can be attributed to rainfall and salt‐wedge movement. The distribution and succession of phytoplankton are influenced by seasonal variation of rainfall and its subsequent effect on the spatial distribution of salinity. The longer duration of rainfall in 1980–81 compared with 1994–95 effectively restricted the movement of the salt‐water wedge, thereby delaying the progression of marine phytoplankton into the estuary. There was little difference in the phytoplankton composition and biomass in the lower estuary, while the upper estuary appeared to have more blooms of dinoflagellates in the summer and autumn of 1994–95 compared with 1980–81.

The intensity and duration of rainfall appeared to affect the availability of soluble nutrients. Although there was no significant difference in phytoplankton biomass between the two periods, it was likely that the high phytoplankton biomass in the upper estuary in 1994–95 was due to availability of more soluble nutrients from internal recycling processes at the sediment/water interface. Copyright © 2001 John Wiley & Sons, Ltd.
Constraining soil hydraulic parameter and output uncertainty of the distributed hydrological MIKE SHE model using the GLUE framework
Authors: Christiaens K. , Feyen J.
Published: August 2002

Both calibration and uncertainty assessment are mandatory steps in today's modelling process. The former considers both the inputs (input variables and parameters) as well as model results. An exploratory investigation of the applicable parameter space results in a wide spectrum of values for a specific model output. By retaining only those model realizations that mimic reality in a sufficient way, inputs and associated response can be constrained, thereby quantifying the uncertainty involved. The generalized likelihood uncertainty estimation (GLUE) framework provides a structured methodology for this purpose.

The study presented focuses on the applicability of the GLUE framework within the context of the distributed hydrological model MIKE SHE. Even though all significant processes involved are incorporated within the model, the problems of calibration and uncertainty assessment cannot be avoided. This has resulted in a quest for well‐delineated effective parameters crucial for sound mechanistic model application. Being a complex model, the number of possible realizations using MIKE SHE is fairly small due to computing time, and an in‐depth exploratory approach is impossible. On the other hand, several output variables are available aside from the hydrological river response, like water content in the soil profile or ground water level, which can be used for retaining realistic parameter sets.

This study presents some preliminary results on the applicability of the GLUE–MIKE SHE framework and associated constrained preliminary parameter and output uncertainty values. Focus was given to the influence of soil hydraulic parameters on the hydrological behaviour of a small study basin. The soil hydraulic parameters were predicted using various pedo‐transfer‐function approaches and moisture retention measurements in the laboratory, and these distributions were then confronted with ranges of the constrained effective parameters. For the latter, the restrictions that were imposed based on behavioural acceptance were substantial. All the traditional methods show significant uncertainty, due to heterogeneity and model error, which cannot be disregarded. The first results suggest a reasonable match among effective parameters and laboratory measurements. The use of pedo‐transfer‐function distributions as effective parameters, however, may provide unacceptable results, even with liberal criteria. Copyright © 2002 John Wiley & Sons, Ltd.
Vascular endothelial growth factor and prognosis in patients with node‐negative breast cancer
Authors: De Paola Franca , Granato Anna Maria , Scarpi Emanuela , Monti Franco , Medri Laura , Bianchi Simonetta , Amadori Dino , Volpi Annalisa
Published: August 2002

Vascular endothelial growth factor (VEGF) has emerged as one of the most important angiogenic growth factors from experimental in vitro and in vivo studies. In the present study, we investigated the relationship between VEGF expression and microvessel density (MVD) and defined their prognostic relevance on a series of 242 patients with node‐negative breast cancer, using immunohistochemical methods. In parallel, estrogen and progesterone receptors were quantitatively assessed using the dextran‐charcoal technique and cell proliferation was evaluated as S‐phase cell fraction according to 3H‐thymidine‐labeling index (TLI). The percentage of VEGF‐expressing cells varied from 0–95% in the different tumors and was unrelated to menopausal status, tumor size or steroid receptor status. Conversely, a significant inverse relation was observed with patient age or tumor cell proliferation, albeit with very poor correlation coefficients. A significant relation was observed between VEGF expression and MVD (rs = 0.55, p < 0.001). Clinical outcome analyzed as a function of high and low VEGF expression showed slight differences in terms of both disease‐free survival (DFS) and overall survival (OS) that never reached statistical significance. Moreover, the trend was paradoxically in favor of patients with highly VEGF‐expressing tumors. Finally, DFS and OS curves, when analyzed as a function of VEGF expression or MVD, were superimposable. In conclusion, our study did not highlight a prognostic relevance of VEGF expression in patients with node‐negative breast cancer, as already observed for MVD. © 2001 Wiley‐Liss, Inc.
Analysis of the antibody repertoire of astrocytoma patients against antigens expressed by gliomas
Authors: Schmits Rudolf , Cochlovius Björn , Treitz Gerhard , Regitz Evi , Ketter Ralf , Preuss Klaus‐Dieter , Romeike Bernd F.M. , Pfreundschuh Michael
Published: August 2002

The molecular characterization of antigens preferentially or exclusively expressed by astrocytomas and recognized by the autologous immune system are a prerequisite for the development of specific vaccines. To identify such antigens, we screened 5 cDNA expression libraries derived from astrocytomas and other gliomas for reactivity with high‐titered IgG antibodies in the sera of astrocytoma patients using SEREX, the serologic identification of antigens by recombinant cDNA expression cloning. Autologous and allogeneic SEREX analysis of >5 × 106 clones with the sera of 18 astrocytoma patients revealed 10 antigens: the differentiation antigen glial fibrillary acidic protein (GFAP), Bax‐inhibitor 1 (which was overexpressed in all glioma samples tested), 3 other molecules involved in the regulation of gene expression and proliferation (the nm23‐H2‐encoded nucleoside diphosphate kinase B, the Ran binding protein‐2 and a DNA binding protein encoded by the son gene), SP40,40 (a complement inhibitory molecule), the chaperonin TCP‐1, calnexin and 2 new gene products. No immune responses were detected against the “shared tumor” or “cancer testis antigens” that are regularly expressed in gliomas. Antibody responses in astrocytoma patients against antigens expressed by gliomas were rare and, with the exception of Bax‐inhibitor 1 and the product of the son gene, were also found in apparently healthy controls. We conclude that although astrocytomas express a broad spectrum of antigens, they elicit antibody responses only rarely, most likely because of their intrinsic immunosuppressive effects. © 2001 Wiley‐Liss, Inc.
Intracellular targeting therapy of cisplatin‐encapsulated transferrin‐polyethylene glycol liposome on peritoneal dissemination of gastric cancer
Authors: Iinuma Hisae , Maruyama Kazuo , Okinaga Kota , Sasaki Katsunori , Sekine Toshiyuki , Ishida Osamu , Ogiwara Naoko , Johkura Kohei , Yonemura Yutaka
Published: August 2002

Peritoneal dissemination in gastric cancer is a common fatal clinical condition with few effective therapies available. We studied the therapeutic effect of a tumor‐targeting drug delivery system that uses cisplatin‐encapsulated and Tf‐conjugated PEG liposomes (Tf‐PEG liposomes) in nude mice with peritoneal dissemination of human gastric cancer cells. Small unilamellar Tf‐PEG, PEG or DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by reverse‐phase evaporation followed by extrusion. Electron microscopic studies revealed that Tf‐PEG liposomes were internalized into tumor cells by receptor‐mediated endocytosis. To examine the biodistribution of each liposome and cisplatin level, nude mice were inoculated i.p. with 107 MKN45P human gastric tumor cells. On the fourth day after tumor inoculation, 3H‐CHE‐labeled and cisplatin‐encapsulated Tf‐PEG, PEG or bare liposome were inoculated i.p. The Tf‐PEG liposome–administered group maintained high liposome and cisplatin levels in ascites and showed a prolonged residence time in the peripheral circulation. Uptake of Tf‐PEG liposomes into the liver and spleen was significantly lower than that of bare liposomes. Uptake of Tf‐PEG liposomes in disseminated tumor cells of ascites and the greater omentum was significantly higher than that of PEG or bare liposomes and a significant increase in cisplatin levels was observed in these tumor cells. Mice receiving Tf‐PEG liposomes 1 and 4 days after the day of tumor inoculation showed significantly higher survival rates compared with those receiving PEG liposomes without Tf, bare liposomes or free cisplatin solution. These results suggest that cisplatin‐encapsulated Tf‐PEG liposomes may be useful as a new intracellular targeting carrier for treatment of gastric cancer with peritoneal dissemination. © 2002 Wiley‐Liss, Inc.
Expression of p53 and its homologues in primary and recurrent squamous cell carcinomas of the head and neck
Authors: Weber Anette , Bellmann Ulf , Bootz Friedrich , Wittekind Christian , Tannapfel Andrea
Published: August 2002

The tumour‐suppressor protein p53 belongs to a family that includes 2 structurally related proteins, p63 and p73. Because of their structural homology, it has been hypothesized that both homologues serve as “spare mechanisms” in p53 mutations to regulate the cell cycle by inducing apoptosis. We investigated the mutational and protein expression status of p53 in correlation to its homologues, p73 and p63, in primary and recurrent squamous cell carcinomas of the head and neck (HNSCC) and corresponding nonneoplastic mucosa. Expression and mutation of p53 and its homologues p63 (including the 2 major isotypes TAp63 and ΔNp63) and p73 was examined by direct DNA sequencing and immunohistochemistry in 29 primary and 39 recurrent (secondary) HNSCCs after microdissection. Our results were correlated with pathohistologic stage and grade. p53 mutations were detected in 32/68 (47%) carcinomas of 17 patients, with a discordant mutation pattern of primary and consecutive tumours in all cases. Positive immunostaining for p63 was found in 55/68 (81%) carcinomas of 29 patients. Immunohistochemistry revealed p73 protein expression in 32/68 (47%) tumours. In normal mucosa, p63 and p73 were expressed in 40/68 (59%) and 12/68 (18%) cases, respectively. We failed to detect specific mutations of p73 or p63 in primary and recurrent carcinoma of the head and neck. p73 and p63 were rarely mutated in HNSCC, but both were expressed in a subset of tumours. The lack of correlation between p73/p63 and p53 protein expression suggests that neither p73 nor p63 can replace p53 when it is mutated. © 2002 Wiley‐Liss, Inc.
Detailed low‐dose study of 1,1‐b™IS(p‐chlorophenyl)‐2,2,2‐ trichloroethane carcinogenesis suggests the possibility of a hormetic effect
Authors: Sukata Tokuo , Uwagawa Satoshi , Ozaki Keisuke , Ogawa Motome , Nishikawa Takayuki , Iwai Syuji , Kinoshita Anna , Wanibuchi Hideki , Imaoka Susumu , Funae Yoshihiko , Okuno Yasuyoshi , Fukushima Shoji
Published: August 2002

To obtain information on the effects of nongenotoxic carcinogens at low doses for human cancer risk assessment, the carcinogenic potential of the organochlorine insecticide, 1,1‐bis(p‐chlorophenyl)‐2,2,2‐trichloroethane (DDT), in the liver was assessed in F344 rats. In experiment 1, 240 male animals, 21 days old, were administered 0, 0.5, 1.0, 2.0, 5.0, 20, 100 and 500 ppm DDT in the diet for 16 weeks. Experiment 2 was conducted to elucidate the carcinogenic potential of DDT at lower levels using 180 rats given doses of 0, 0.005, 0.01, 0.1, 0.2 and 0.5 ppm. The livers of all animals were immunohistochemically examined for expression of glutathione S‐transferase placental form (GST‐P), putative preneoplastic lesions. Quantitative values for GST‐P‐positive foci in the liver were increased dose‐dependently in rats given 20 ppm DDT and above with statistical significance as compared with the concurrent control value. In contrast, doses of 0.005 and 0.01 ppm were associated with a tendency for decrease below the control value, although not significantly. Western blotting analysis show that cytochrome P‐450 3A2 (CYP3A2) protein expression tended to decrease at 0.005 and 0.01 ppm, a good correlation being observed with the change in the number of GST‐P‐positive foci. These findings suggest that a DDT hepatocarcinogenicity may show nonlinear response, that is, hormetic response at low doses. Furthermore, since CYP3A2 protein expression appears to be important for the effects of phenobarbital and the α‐isomer of benzene hexachloride, mRNAs for IL‐1 receptor type 1 (IL‐1R1) and TNF‐α receptor type 1 (TNFR1) whose ligands have roles not only in downregulating CYP3A2 expression but also in inducing antiproliferative effect or apoptosis in hepatocyte were examined. Increase was observed at low doses of DDT. Oxidative stress in liver DNA, assessed in terms of 8‐hydroxydeoxyguanosine as a marker, was also decreased. These findings suggest that the possible hormetic effect that was observed in our detailed low‐dose study of DDT carcinogenesis, although not statistically significant, may be linked to levels of oxidative stress and proinflammatory cytokines. © 2002 Wiley‐Liss, Inc.
Dietary risk factors for upper aerodigestive tract cancers
Authors: Kasum Christine M. , Jacobs David R. , Nicodemus Kristin , Folsom Aaron R.
Published: August 2002

We examined the association between whole‐grain intake and incident upper aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer‐free women. We also studied established risk factors for upper aerodigestive cancers, including fruit and vegetable intake, smoking and alcohol intake. A mailed questionnaire at baseline in 1986 included a food‐frequency questionnaire and assessment of other cancer risk factors. During the 14‐year follow‐up period, 169 women developed cancer of the upper aerodigestive tract. For all upper aerodigestive cancers together, significant inverse associations were observed for the highest compared to the lowest tertile of whole grains [relative risk (RR) = 0.53, 95% confidence interval (CI) 0.34–0.81] and yellow/orange vegetables (RR = 0.58, 95% CI 0.39–0.87). In addition, those in the highest compared to lowest tertile of fiber intake from whole grain were less likely to develop upper aerodigestive tract cancer (RR = 0.56, 95% CI 0.37–0.84); fiber intake from refined grain was not significantly associated with upper aerodigestive tract cancer. Findings were generally similar for oropharyngeal (n = 53), laryngeal (n = 21), nasopharyngeal/salivary (n = 18), esophageal (n = 21) and gastric (n = 56) cancers, though numbers of cases were too small for statistical testing within individual cancers. These findings confirm previous observations that high intake of fruits and vegetables and that intake of whole grains and the fiber derived from them may reduce risk of upper aerodigestive tract cancers. © 2002 Wiley‐Liss, Inc.
An artificial neural network considerably improves the diagnostic power of percent free prostate‐specific antigen in prostate cancer diagnosis: Results of a 5‐year investigation
Authors: Stephan Carsten , Jung Klaus , Cammann Henning , Vogel Birgit , Brux Brigitte , Kristiansen Glen , Rudolph Birgit , Hauptmann Steffen , Lein Michael , Schnorr Dietmar , Sinha Pranav , Loening Stefan A.
Published: August 2002

Our study was performed to evaluate the diagnostic usefulness of %fPSA alone and combined with an ANN at different PSA concentration ranges, including the low range 2–4 ng/ml, to improve the risk assessment of prostate cancer. A total of 928 men with prostate cancer and BPH without any pretreatment of the prostate in the PSA range 2–20 ng/ml were enrolled in the study between 1996 and 2001. An ANN with input data of PSA, %fPSA, patient's age, prostate volume and DRE status was developed to calculate the individual's risk before performing a prostate biopsy within the different PSA ranges 2–4, 4.1–10 and 10.1–20 ng/ml. ROC analysis and cut‐off calculations were used to estimate the diagnostic improvement of %fPSA and ANN in comparison to PSA. At the 90% sensitivity level, %fPSA and ANN performed better than PSA in all ranges, enhancing the specificity by 15–28% and 32–44%, respectively. For the low PSA range 2–4 ng/mL, we recommend a first‐time biopsy at an ANN specificity level of 90%. For PSA 4–10 ng/mL, we recommend a first‐time biopsy based on the ANN at the 90% sensitivity level. Use of an ANN enhances the %fPSA performance to further reduce the number of unnecessary biopsies within the PSA range 2–10 ng/ml. © 2002 Wiley‐Liss, Inc.
Transformation by inorganic arsenic compounds of normal Syrian hamster embryo cells into a neoplastic state in which they become anchorage‐independent and cause tumors in newborn hamsters
Authors: Takahashi Masayuki , Barrett J. Carl , Tsutsui Takeki
Published: August 2002

Arsenic is a known human carcinogen, but little evidence exists for its carcinogenicity in animals. In order to investigate the ability of inorganic arsenics to transform normal cells into a neoplastic state, mass cultures of normal, diploid Syrian hamster embryo (SHE) cells exposed to various concentrations of sodium arsenite or sodium arsenate for 48 hr were continually passaged and tested for neoplastic transformation, as determined by anchorage‐independent growth in semisolid agar and tumorigenicity in newborn hamsters. Twenty‐one of 22 (96%) untreated, control cultures senesced by 20 passages. While 1 culture escaped senescence, it did not acquire the ability to either grow in semisolid agar or form tumors in animals. Ten of 14 (71%) cultures exposed to sodium arsenite or sodium arsenate escaped senescence. Nine of the 10 (90%) arsenic‐treated immortal cultures acquired the anchorage‐independent phenotype. Five of 5 anchorage‐independent cultures examined were tumorigenic. Two of 3 morphologically transformed colonies induced by sodium arsenate also acquired the ability to grow in semisolid agar when isolated. Amplification of the c‐myc or c‐Ha‐ras oncogene was detected in 3 of 5 and 4 of 5 tumorigenic cell lines, respectively. Both c‐myc and c‐Ha‐ras were amplified even in a preneoplastic, anchorage‐dependent cell line, but neither was amplified in 6 of 9 anchorage‐independent cell lines. Overexpression of c‐myc and c‐Ha‐ras mRNA was observed in most of the neoplastically transformed cell lines but not in the preneoplastic cell line. Experiments using the methylation‐sensitive restriction endonuclease isoschizomers HpaII and MspI revealed hypomethylation of c‐myc and c‐Ha‐ras in the 5′‐CCGG sequence of arsenic‐exposed cell lines but not in the parental SHE cells or a spontaneously transformed cell line. Thus, inorganic arsenics induce neoplastic transformation of normal, diploid mammalian cells. Overexpression of oncogenes by DNA hypomethylation may participate in the arsenic‐induced neoplastic transformation of mammalian cells. Published 2002 Wiley‐Liss, Inc.