bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen receptors in the embryonic zebra finch hindbrain suggest a function for maternal androgens in perihatching survival
Authors: Godsave Susan F. , Lohmann Ragna , Vloet Rianka P.M. , Gahr Manfred
Published: October 2002

Bird embryos are exposed to maternal androgens deposited in the egg, but the role of these hormones in embryonic development and hatchling survival is unclear. To identify possible target organs, we used in situ hybridization to study the distribution of androgen receptor (AR) RNA in the developing zebra finch brain. The first brain expression domain of AR mRNA is in the hindbrain. From embryonic day 7 (E7) onward, when the hypoglossal motor nucleus (nXII) has just formed, there was AR mRNA expression in both its lingual (nXIIl) and its tracheosyringeal (nXIIts) parts, and this was the major site of hindbrain expression at all embryonic stages and in both sexes. From E8 onward, we also found AR mRNA in the supraspinal motor nucleus (nSSp), which innervates neck muscles. Furthermore, the syrinx, the target of the nXIIts, contained AR mRNA by E10, localized principally in the perichondria. Muscle was first evident in the syringeal region at E9, but no AR was detected in syringeal muscles until after hatching. The expression pattern of AR in the zebra finch embryo suggests that maternal androgens act via AR in the brainstem and syrinx to influence hatching as well as acoustic and visual components of food‐begging behavior. Maternal androgens seem unlikely to function in the development of sexual dimorphisms in the zebra finch nXIIts and syrinx, insofar as these are not evident until between 10 and 20 days posthatching. J. Comp. Neurol. 453:57–70, 2002. © 2002 Wiley‐Liss, Inc.
Boundary concentration phenomena for a singularly perturbed elliptic problem
Authors: Malchiodi Andrea , Montenegro Marcelo
Published: October 2002

We exhibit new concentration phenomena for the equation − ε2 Δu + u = up in a smooth bounded domain Ω ⊆ ℝ2 and with Neumann boundary conditions. The exponent p is greater than or equal to 2 and the parameter ε is converging to 0. For a suitable sequence εn → 0 we prove the existence of positive solutions un concentrating at the whole boundary of Ω or at some component. © 2002 Wiley Periodicals, Inc.
Simulating multiple inheritance in Java
Authors: Lyon Douglas
Published: October 2002

TheCentiJsystem automatically generates code that simulates multiple inheritance in Java. The generated code inputs a series of instances and outputs specifications that can be combined using multiple inheritance. The multiple inheritance of implementation is obtained by simple message forwarding. ThereflectionAPI of Java is used to reverse engineer the instances, and so the program can generate source code, but does not require source code on its input. Advantages ofCentiJinclude compile‐time type checking, speed of execution, automatic disambiguation (name space collision resolution) and ease of maintenance.

Simulation of multiple inheritance was previously available only to Java programmers who performed manual delegation or who made use of dynamic proxies. The technique has been applied at a major aerospace corporation. Copyright © 2002 John Wiley & Sons, Ltd.
Detection of in situ activation of transglutaminase during apoptosis: Correlation with the cell cycle phase by multiparameter flow and laser scanning cytometry
Authors: Grabarek Jerzy , Ardelt Barbara , Kunicki Jan , Darzynkiewicz Zbigniew
Published: October 2002

Background

One of the hallmarks of apoptosis is activation of tissue transglutaminase (Tgase; also called transglutaminase type 2 [TGase 2]). Its activation causes cross‐linking of cytoplasmic proteins, making them insoluble and presumably less immunogenic. Several biochemical and cytochemical methods to detect activity of TGase 2 exist, but none has been adapted for multiparameter flow or image cytometry.

Methods

Apoptosis of HL‐60 or U‐937 leukemic cells was induced by camptothecin, tumor necrosis factor α, hyperthermia, or the cytotoxic RNase onconase. Two different approaches to detect TGase 2 activation were developed: (a) the unfixed cells were treated with 4′,6′‐diamidino‐2‐phenylindole, and sulforhodamine 101 in solutions of nonionic detergents; (b) the TGase 2 substrate fluoresceinated polyamine cadaverine (F‐CDV) was administered into the cultures for several hours before cell harvesting. The cells were then fixed and their DNA counterstained with propidium. Cellular fluorescence was measured by flow or laser scanning cytometry.

Results

(a) Exposure of nonapoptotic cells to detergents caused their full lysis, resulting in preparation of isolated nuclei devoid of cytoplasm. Conversely, the cross‐linking of cytoplasmic protein by activated TGase 2 in apoptotic cells provided resistance to detergents: the nuclei or nuclear (chromatin) fragments of apoptotic cells remained attached to the cytoplasmic protein, embedded within the proteinaceous “shell.” Such cells were identified by their high protein content: intensity of fluorescence after staining with the protein fluorochrome sulforhodamine 101 was markedly higher than that of isolated nuclei. (b) Activation of TGase 2 was also detected by virtue of intense cell labeling with fluoresceinated polyamine cadaverine. Interestingly, in many cells apoptosis progressed without evidence of activation of TGase 2, suggesting that this event may not be a prerequisite for completion of apoptosis.

Conclusions

Activation of TGase 2 can be detected simply by cell resistance to detergents or in situ reactivity with F‐CDV. Both methods allow one to correlate activation of TGase 2 with the cell cycle position. However, because activation of TGase 2 is not always detected during apoptosis, the lack of the activation cannot be considered a marker of nonapoptotic cells. Hence, an apoptotic index based solely on TGase 2 activation may underestimate incidence of apoptosis. Cytometry 49:83–89, 2002. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of a case of HIV‐associated anaplastic myeloma
Authors: Stewart John M.M. , Krishnamurthy Savitri
Published: October 2002

Plasma cell neoplasia occurs much less frequently than high‐grade B‐cell non‐Hodgkins lymphoma in HIV‐infected patients, but is nevertheless an AIDS‐associated malignancy. In this report, we describe the fine‐needle aspiration (FNA) findings of a mass in the left parotid region with plasmablastic features that occurred in a 41‐yr‐old HIV‐infected homosexual man whom we diagnosed as having anaplastic myeloma. The patient had normochromic, normocytic anemia with a hematocrit of 21%, a white blood count of 2.2 × 109/l with 76% neutrophils, and a CD4 count of 31%. He also had elevated levels of calcium (13.2 mg/dl), alkaline phosphatase (25,400 IU/l), blood urea nitrogen (2,600 mg/dl), and creatinine (2.5 mg/dl). Serum protein electrophoresis showed polyclonal hypergammaglobulinemia without any monoclonal component. A bone survey revealed multiple punched‐out lytic lesions. FNA smears showed large plasmacytoid cells with eccentrically placed nuclei, prominent nucleoli, and moderate amounts of basophilic cytoplasm. By immunocytochemical staining, tumor cells were negative for CD19, CD20, and leukocyte‐common antigen (LCA), but strongly positive for CD38 and kappa light chain.

Anaplastic myeloma and plasmablastic lymphoma were considered in the differential diagnosis. Although the cytomorphologic and immunophenotypic findings of our case overlapped with those of plasmablastic lymphoma, the pattern of bone involvement with punched‐out lytic lesions and absence of localization of the tumor to the mucosa of the oral cavity led us to a diagnosis of anaplastic myeloma. The patient initially received antiretroviral therapy followed by thalidomide and pulse dexamethasome therapy, but his response was poor. His HIV load increased, and his malignancy rapidly progressed with the development of multiple vertebral lesions, extraosseous extension, and eventually cord compression. He died of the disease less than 2 mo after presentation. Diagn. Cytopathol. 2002;27:218–222. © 2002 Wiley‐Liss, Inc.
Metals and oxidative homeostasis in Alzheimer's disease
Authors: Perry George , Cash Adam D. , Srinivas Ravi , Smith Mark A.
Published: October 2002

Oxidative damage to every class of biological macromolecule has been characterized in Alzheimer's disease. Abnormalities in iron and copper metabolism are also being implicated as playing a crucial role in neurodegenerative disease pathogenesis. Metal homeostasis as it pertains to alterations in brain function in neurodegenerative diseases is reviewed here with its relationship to oxidative stress. While there is documented evidence for alterations in transition metal homeostasis, redox‐activity, and localization, it is also important to realize that alterations in specific copper‐ and iron‐containing metalloenzymes also contribute to the neurodegenerative process. These changes offer the opportunity to identify pathways where modification of the disease process can offer new routes for clinical efficacy, from gene therapy to use of antioxidant and chelating drugs. Drug Dev. Res. 56:293–299, 2002. © 2002 Wiley‐Liss, Inc.
Regulated expression of α2B adrenoceptor during development
Authors: Wang Guey‐Shin , Chang Nan‐Chi , Wu Shinn‐Chih , Chang Alice Chien
Published: October 2002

There are three subtypes of α2 adrenoceptor, i.e., α2A, α2B, and α2C, mediating the specific effect of epinephrine and norepinephrine in various tissues by means of G protein–coupled signal transduction pathways. In an attempt to delineate the regulatory mechanism of the α2B receptor subtype (encoded by subtype gene Adra2b) expression in the central nervous system (CNS), we have established transgenic (Tg) mice lines in which the transgene (NN‐lacZ) was composed of the promoter region of Adra2b (NcoI fragment, 4.7 kb immediately upstream from receptor coding region) and a reporter gene lacZ (encoding β‐galactosidase). The selective expression of α2B in brain as indexed by β‐galactosidase, under the direction of this promoter region, may be traced in situ by using X‐gal staining. The expression pattern of Adra2b‐NN‐lacZ in CNS of Tg mice during development was examined. The temporal course of examination was from gestation day 9.5 (E9.5) to postnatal day 28 (P28). Significant X‐gal staining was detected in the dorsal root ganglion and cranial nerves V and VII at E12.5. By E18.5, expression was noted in the cerebral cortex, anterior olfactory nucleus, hypothalamus, brainstem, and cerebellar Purkinje cells, among others, and persisted through postnatal development. Adra2b‐NN–directed reporter expression was detected in the hippocampal dentate gyrus first at P4. The temporal course of expression up to P28 in this area is in accordance with the developmental profiles of granule neurons of dentate gyrus. From P7 on, transgene expression was detected in additional brain areas, including the septum and thalamus. The expression correlates well with the noradrenergic innervations as evidenced by colocalization by using tyrosine hydroxylase or dopamine‐β‐hydroxylase immunocytochemistry. © 2002 Wiley‐Liss, Inc.
Disruption of anterior segment development by TGF‐β1 overexpression in the eyes of transgenic mice
Authors: Flügel‐Koch Cassandra , Ohlmann Andreas , Piatigorsky Joram , Tamm Ernst R.
Published: October 2002

Previous experiments showed that transgenic mice expressing a secreted self‐activating transforming growth factor (TGF) ‐β1 did not show a phenotype in the lens and cornea until postnatal day 21, when anterior subcapsular cataracts, sporadic thickening of the corneal stroma, and thinning of the corneal epithelium were noted (Srinivasan et al., 1998). To examine the effects of higher concentrations of TGF‐β1 on the lens and cornea, we constructed transgenic mice harboring the strong, lens‐specific chicken βB1‐crystallin promoter driving an activated porcine TGF‐β1 gene. In contrast to the earlier study, the transgenic mice had microphthalmic eyes with closed eyelids. Already at embryonic day (E) 13.5, the future cornea of the transgenic mice was threefold thicker than that of wild‐type littermates due to increased proliferation of corneal stromal mesenchyme cells. Staining of fibronectin and thrombospondin‐1 was increased in periocular mesenchyme. At E17.5, the thickened transgenic corneal stroma was vascularized and densely populated by abundant star‐shaped, neural cell adhesion molecule–positive cells of mesenchymal appearance surrounded by irregular swirls of collagen and extracellular matrix. The corneal endothelium, anterior chamber, and stroma of iris/ciliary body did not develop, and the transgenic cornea was opaque. Fibronectin, perlecan, and thrombospondin‐1 were elevated, whereas type VI collagen decreased in the transgenic corneal stroma. Stromal mesenchyme cells expressed α‐smooth muscle actin as did lens epithelial cells and cells of the retinal pigmented epithelium. By E17.5, lens fiber cells underwent apoptotic cell death that was followed by apoptosis of the entire anterior lens epithelium between E18.5 and birth. Posteriorly, the vitreous humor was essentially absent; however, the retina appeared relatively normal. Thus, excess TGF‐β1, a mitogen for embryonic corneal mesenchyme, severely disrupts corneal and lens differentiation. Our findings profoundly contrast with the mild eye phenotype observed with presumably lower levels of ectopic TGF‐β and illustrate the complexity of TGF‐β utilization and the importance of dose when assessing the effects of this growth factor. © 2002 Wiley‐Liss, Inc.
Malsegregation as a possible mechanism of aneuploidy induction by metal salts in MRC‐5 human cells
Authors: Seoane A.I. , Güerci A.M. , Dulout F.N.
Published: October 2002

Many aneugenic compounds are known to affect one or more components of the mitotic apparatus leading to an erroneous migration of chromosomes. Malsegregation occurs when a chromosome (or a chromatid) fails to migrate and remains at the metaphase plate. Nondisjunction implies the lack of dissociation between sister chromatids and the migration of both together to the same pole. The aim of the present study was to provide evidence that the aneugenic effect of some metal salts is the consequence of malsegregation at anaphase and that it is not caused by nondisjunction mechanisms. The frequencies of lagging chromosomes at anaphase‐telophase of mitosis, hypoploid metaphases, and kinetochore‐positive micronuclei induced by cadmium chloride, potassium dichromate, and cacodilic acid (dimethylarsinic acid) in MRC‐5 human cells were compared. The data indicate that all the tested compounds are able to induce aneuploidy in MRC‐5 human cells. Positive, statistically significant correlations were found when kinetochore‐positive micronuclei, hypoploidy, and lagging chromosome frequencies were compared. The results suggest that malsegregation is the main mechanism involved in the induction of aneuploidy by metal salts in MRC‐5 cells. Environ. Mol. Mutagen. 40:200–206, 2002. © 2002 Wiley‐Liss, Inc.
Analysis of particulate matter air pollution using Markov random field models of spatial dependence
Authors: Kaiser Mark S. , Daniels Michael J. , Furakawa Kyoji , Dixon Philip
Published: October 2002

Researchers are beginning to realize the need to take spatial structure into account when modeling data on air pollutants. We develop several models for particulate matter in an urban region that allow spatial dependence to be represented in different manners over a time period of one year. The models are based on a Markov random field approach, and a conceptualization of observed data as arising from two random processes, a conditionally independent observation process and a spatially dependent latent pollution process. Optimal predictors are developed for both of these processes, and predictions of the observation process are used for model assessment. Copyright © 2002 John Wiley & Sons, Ltd.
Modelling three‐dimensional non‐linear seismic performance of elevated bridges with emphasis on pounding of girders
Authors: Zhu Ping , Abe Masato , Fujino Yozo
Published: October 2002

Unseating of bridge girders/decks during earthquakes is very harmful to the safety and serviceability of bridges. Evidence from recent severe earthquakes indicates that in addition to damage along longitudinal direction, lateral displacement and rotation of bridge girders caused by pounding to adjacent girders can also lead to unseating. To simulate this effect, 3D modelling of the dynamic performance of whole bridge structures, including pounding, is needed strongly. This paper presents a 3D model that is practically suitable to precisely analyse pounding between bridge girders. Experiments have been conducted to verify the proposed pounding model. The 3D non‐linear modelling of steel elevated bridges is also discussed. A general‐purpose dynamic analysis program for bridges, namely dynamic analysis of bridge systems (DABS) has been developed. Seismic analyses on a chosen three‐span steel bridge are conducted for several cases including pounding as a case study. The applicability of the proposed pounding model is illustrated by the computations. The effects of poundings on the response of bridge girders are discussed and the computation results are given. Copyright © 2002 John Wiley & Sons, Ltd.
Upscaling: a review
Authors: Farmer C. L.
Published: October 2002

Porous media have properties with heterogeneities on several length scales. It is possible to build digital models of such properties. However these can be so detailed that a computing machine of the same power as that used to build the property model is not able to solve the fluid flow equations using standard discretisation methods—storage is needed for workspace, and the discrete equations have to be solved in a reasonable time. This paper reviews averaging techniques, devised to simulate large scale features of solutions without necessarily solving all the fine scale equations. Copyright © 2002 John Wiley & Sons, Ltd.
Implicit fluid–structure coupling for simulation of cardiovascular problems
Authors: Penrose J. M. T. , Staples C. J.
Published: October 2002

A three‐dimensional (3‐D) transient solid–fluid coupling system has been developed in order to study cardiovascular systems and devices. The system utilized two commercial implicit solvers, which exchanged boundary parameters from separate meshes over a common interface. Facility was made for the spatial interpolation of these exchange parameters so that the solid and fluid domain meshes need not have similar density or topology. Stability algorithms were added to the iterative coupling process, as were algorithms to smooth or entirely remesh the fluid domain interior subject to the deformations imposed at the solid–fluid interface. Several application scenarios were undertaken, whereby simulation results could be compared to either analytical or detailed experimental data. It was hoped they would also offer further insight into the operation of a number of clinical devices. The results of these comparisons show that the simulation of complex cardiac systems, with non‐linear solid–fluid interactions, can now be achieved with sufficient accuracy to be of significant benefit to manufacturers. Copyright © 2002 John Wiley & Sons, Ltd.
Reciprocal translocations in breast tumor cell lines: Cloning of a t(3;20) that targets the FHIT gene
Authors: Popovici Cornel , Basset Céline , Bertucci François , Orsetti Béatrice , Adélaide José , Mozziconacci Marie‐Joëlle , Conte Nathalie , Murati Anne , Ginestier Christophe , Charafe‐Jauffret Emmanuelle , Ethier Stephen P. , Lafage‐Pochitaloff Marina , Theillet Charles , Birnbaum Daniel , Chaffanet Max
Published: October 2002

All molecular alterations that lead to breast cancer are not precisely known. We are evaluating the frequency and consequences of reciprocal translocations in breast cancer. We surveyed 15 mammary cell lines by multicolor fluorescence in situ hybridization (M‐FISH). We identified nine apparently reciprocal translocations. Using mBanding FISH and FISH with selected YAC clones, we identified the breakpoints for four of them, and cloned the t(3;20)(p14;p11) found in the BrCa‐MZ‐02 cell line. We found that the breakpoint targets the potential tumor‐suppressor gene FHIT (fragile histidine triad) in the FRA3B region; it is accompanied by homozygous deletion of exon 5 of the gene and absence of functional FHIT and fusion transcripts, which leads to the loss of FHIT protein expression. Additional experiments using comparative genomic hybridization provided further information on the genomic context in which the t(3;20)(p14;p11) reciprocal translocation was found. © 2002 Wiley‐Liss, Inc.
Domiciliary clinics I: effects on non‐attendance
Authors: Anderson D. N. , Aquilina C.
Published: October 2002

Objective

To compare the rate of non‐attendance for new referrals to a hospital based clinic versus home assessment.

Setting

Two old age psychiatry services in an urban area.

Method

A four year prospective study comparing rates of non‐attendance for new referrals to a hospital based clinic versus assessment at home in two parallel old age psychiatry services.

Results

The rate of non‐attendance for new referrals seen at home was considerably lower (1.7%) than the hospital based clinic (21.2%).

Conclusions

Assessing new outpatient referrals to old age psychiatry services at home reduces non‐attendance. This improves efficient use of medical time in a small geographical catchment area but may not apply to rural or larger areas. Copyright © 2002 John Wiley & Sons, Ltd.
Superbugs II: how should economic evaluation be conducted for interventions which aim to contain antimicrobial resistance?
Authors: Coast Joanna , Smith Richard , Karcher Anne‐Marie , Wilton Paula , Millar Michael
Published: October 2002

To date, there has been little examination of the problems associated with conducting economic evaluation for interventions designed to contain antimicrobial resistance. There are two quite different types of intervention aimed at containing antimicrobial resistance: interventions which are designed to avoid the emergence of resistant organisms; and interventions that are designed to avoid the transmission of resistance organisms. Four aspects of economic evaluation where the ease of assessment might be expected to differ across evaluations for these different types of intervention are examined: problems associated with the identification of diffuse impacts, problems associated with comparing current and future impacts, problems associated with uncertainty, and problems associated with difficulties in measurement and valuation. The paper suggests that it may be much easier to conduct rigorous economic evaluations for interventions designed to avoid transmission of resistance, than for those intended to avoid emergence. Unfortunately, the transmission policies, which are likely to be the easiest to evaluate, are not likely to produce an optimal long‐term outcome given the apparent irreversability of much resistance and the potentially severe harms which could be imposed as a result. Given the desirability of avoiding a scenario where, in the evidence‐based medicine culture, the most rigorously evaluated policies are followed even though they may be less important, there is the need to consider carefully what, and how, economic evaluation should be conducted in the area of antimicrobial resistance. It is suggested that research should focus on the use of modelling as a means of evaluating optimal policy responses and on trying to resolve some of the difficulties associated with measurement and valuation. Copyright © 2002 John Wiley & Sons, Ltd.
Feasibility of supraomohyoid neck dissection in N1 and N2a oral cancer patients
Authors: Kowalski Luiz P. , Carvalho André L.
Published: October 2002

Background

The use of selective neck dissection in a positive neck is still controversial. The object of this study was to ascertain the possibility of doing this procedure in oral cavity carcinoma with a single clinically metastatic lymph node smaller than 6 cm (N1 and N2a).

Patients and Methods

From 1970 to 1994, we analyzed 164 oral cavity cancer patients with clinically N1 or N2a stage cancer submitted to radical neck dissection.

Results

The histologic findings did not confirm a metastatic lymph node in 69 (42.1%) cases (pN0) and showed multiple lymph nodes in 19 (11.6%) cases. Moreover, just one patient (0.6%) had a metastatic lymph node at level IV (one case with multiple lymph nodes) and none at level V.

Conclusions

Because we did not find a single metastatic lymph node at levels IV and V and there was a high incidence of pN0 (57.4%) in patients with clinical N1 stage at level I, these patients could be candidates for a supraomohyoid neck dissection (extended or not to level IV) instead of radical neck dissection. © 2002 Wiley Periodicals, Inc.
An analysis framework for applying virtual environment technology to manufacturing tasks
Authors: Chung Kyung H. , Shewchuk John P. , Williges Robert C.
Published: October 2002

An empirical approach for improving the applicability of a virtual environment (VE) technology to manufacturing tasks is presented and discussed by considering the technological and economical perspectives. The three‐step analysis framework, which consists of evaluating overall feasibility, assessing potential benefits, and conducting cost/benefits analysis, was developed to support researchers in choosing an appropriate VE method and in designing a cost‐effective VE application. The usefulness and limitation of the framework were reviewed with a case study in which VE technology was used to improve the performance of dimensional inspection tasks as a means of providing the initial validation of the analysis framework. © 2002 Wiley Periodicals, Inc.
Cultivating problem‐solving skills through problem‐based approaches to professional development
Authors: Lohman Margaret C.
Published: October 2002

An extensive literature review was conducted of four problem‐based approaches to professional

development: (1) case study, (2) goal‐based scenario, (3)

problem‐based learning, and (4) action learning. The review comparatively analyzed the training

designs of these four approaches and found key differences in the nature of their case problems and training

strategies. Specifically, the analysis found that case problems are ill structured in action learning and

problem‐based learning, are moderately structured in a goal‐based scenario, and are fairly well

structured in the case study approach. In addition, it was found that prototypical problems are used to a much

greater extent in the problem‐based learning and goal‐based scenario approaches than they are in

the other two approaches. Furthermore, the analysis found that the case study approach uses the most

expert‐oriented training strategy, the goal‐based scenario approach uses a more

learner‐oriented strategy than the case study approach, and the problem‐based learning and action

learning approaches use strongly learner‐oriented strategies. These design differences suggest that the

case study and goal‐based scenario approaches are more likely to result in single‐loop learning and

to foster the ability to solve well‐structured problems, whereas the problem‐based learning and

action learning approaches are more likely to lead to double‐loop learning and to promote the ability to

solve ill‐structured problems. Implications of these findings for the design and research of

problem‐based approaches to professional development are discussed.
Relationships between accountability, job satisfaction, and trust
Authors: Thoms Peg , Dose Jennifer J. , Scott Kimberly S.
Published: October 2002

With the trend toward self‐management comes increasing accountability of individuals to their coworkers

and organizations. There is an implicit assumption that workers like self‐management and the accompanying

accountability, despite little supporting empirical evidence. This study examines the idea that workers'

perceptions of their level of accountability are related to their job satisfaction. A significant correlation was

found between job satisfaction and perceived accountability to coworkers and perceived accountability to management.

In addition, we found that accountability to both coworkers and management was positively related to trust in

supervisors and managers. However, only two aspects of accountability—manager and coworker

awareness—seem to explain the variance in job satisfaction and trust. Practical applications of the findings

are explained.
Effect of snowpack removal on energy balance, melt and runoff in a small supraglacial catchment
Authors: Willis Ian C. , Arnold Neil S. , Brock Ben W.
Published: October 2002

Modelling melt and runoff from snow‐ and ice‐covered catchments is important for water resource and hazard management and for the scientific study of glacier hydrology, dynamics and hydrochemistry. In this paper, a distributed, physically based model is used to determine the effects of the up‐glacier retreat of the snowline on spatial and temporal patterns of melt and water routing across a small (0·11 km2) supraglacial catchment on Haut Glacier d'Arolla, Switzerland. The melt model uses energy‐balance theory and accounts for the effects of slope angle, slope aspect and shading on the net radiation fluxes, and the effects of atmospheric stability on the turbulent fluxes. The water routing model uses simplified snow and open‐channel hydrology theory and accounts for the delaying effects of vertical and horizontal water flow through snow and across ice. The performance of the melt model is tested against hourly measurements of ablation in the catchment. Calculated and measured ablation rates show a high correlation (r2 = 0·74) but some minor systematic discrepancies in the short term (hours). These probably result from the freezing of surface water at night, the melting of the frozen layer in the morning, and subsurface melting during the afternoon. The performance of the coupled melt/routing model is tested against hourly discharge variations measured in the supraglacial stream at the catchment outlet. Calculated and measured runoff variations show a high correlation (r2 = 0·62). Five periods of anomalously high measured discharge that were not predicted by the model were associated with moulin overflow events. The radiation and turbulent fluxes contribute c. 86% and c. 14% of the total melt energy respectively. These proportions do not change significantly as the surface turns from snow to ice, because increases in the outgoing shortwave radiation flux (owing to lower albedo) happen to be accompanied by decreases in the incoming shortwave radiation flux (owing to lower solar incidence angles) and increases in the turbulent fluxes (owing to higher air temperatures and vapour pressures). Model sensitivity experiments reveal that the net effect of snow pack removal is to increase daily mean discharges by c. 50%, increase daily maximum discharges by >300%, decrease daily minimum discharges by c. 100%, increase daily discharge amplitudes by >1000%, and decrease the lag between peak melt rates and peak discharges from c. 3 h to c. 50 min. These changes have important implications for the development of subglacial drainage systems. Copyright © 2002 John Wiley & Sons, Ltd.
A new interpretation of kinematic stormflow generation
Authors: Williams A. G. , Dowd J. F , Meyles E. W.
Published: October 2002

The paper reviews a number of possible fast and slow hydrological flow mechanisms to account for rapid runoff generation within a catchment. A new interpretation of the kinematic wave process is proposed which develops some of these concepts to explain rapid subsurface flow from a watershed. Evidence for the process is provided by the results from a laboratory soil core experiment and an investigation of the hydrology of a Dartmoor hillslope. A tension response was monitored in the soil core in which pressure waves were propagated downwards and expelled water from the base. The transmission of the wave down the core was considerably faster than the movement of a chloride tracer. The concept of this kinematic wave process and associated water flux was then extended to the Dartmoor watershed. Raindrops reaching the wet soil surface caused pressure waves to travel laterally downslope. During large rainstorms, the hillslope became hydrologically highly connected and the pressure waves forced existing water from seepage faces into the saturated area adjacent to the stream, contributing substantially to the stream discharge. A kinematic contributing area was defined, as determined by both rainfall–runoff ratios and geostatistical analyses of hillslope soil moisture contents, which extended over at least 65% of the catchment area. This kinematic wave theory is consistent with results of translatory flow and macropore flow models, and stable isotope field studies of ‘old/new’ water. Copyright © 2002 John Wiley & Sons, Ltd.
Establishment and characterisation of a human clear cell sarcoma model in nude mice
Authors: Crnalic Sead , Panagopoulos Ioannis , Boquist Lennart , Mandahl Nils , Stenling Roger , Löfvenberg Richard
Published: October 2002

We have established a new experimental model of human clear cell sarcoma, UM‐CCS1, using serial subcutaneous transplantation of intact tumour tissue in nude mice. The heterotransplanted nude mouse tumours retained characteristic morphological features of the primary clear cell sarcoma. Immunohistochemical analysis showed the retained expression patterns of S‐100 protein, melanoma‐associated antigen HMB‐45 and vimentin in the xenografts as compared to the primary tumour. DNA index showed low variations both between the xenografts in the same passage and between the serial passages. Cytogenetic analysis of the primary tumour and the xenografts showed the unbalanced translocation der(6)t(6;12)(p23;q13). Based on the combined genetic data a reasonable interpretation of our findings is that there was a complex chromosomal rearrangement resulting in a cytogenetically cryptic EWS‐ATF1 fusion gene. Analysis of cell kinetics using in vivo incorporation of iododeoxyuridine and flow cytometry showed generally short potential doubling time (Tpot) of the xenografts. Volume doubling time showed low variations without correlation with Tpot. The retained phenotypic and genotypic characteristics of the primary tumour and the morphological and structural stability over time makes the model suitable for studies on the tumour biology and treatment of clear cell sarcoma. © 2002 Wiley‐Liss, Inc.
Automated diagnosis of pigmented skin lesions
Authors: Rubegni Pietro , Cevenini Gabriele , Burroni Marco , Perotti Roberto , Dell'Eva Giordana , Sbano Paolo , Miracco Clelia , Luzi Pietro , Tosi Piero , Barbini Paolo , Andreassi Lucio
Published: October 2002

Since advanced melanoma remains practically incurable, early detection is an important step toward a reduction in mortality. High expectations are entertained for a technique known as dermoscopy or epiluminescence light microscopy; however, evaluation of pigmented skin lesions by this method is often extremely complex and subjective. To obviate the problem of qualitative interpretation, methods based on mathematical analysis of pigmented skin lesions, such as digital dermoscopy analysis, have been developed. In the present study, we used a digital dermoscopy analyzer (DBDermo‐Mips system) to evaluate a series of 588 excised, clinically atypical, flat pigmented skin lesions (371 benign, 217 malignant). The analyzer evaluated 48 parameters grouped into 4 categories (geometries, colors, textures and islands of color), which were used to train an artificial neural network. To evaluate the diagnostic performance of the neural network and to check it during the training process, we used the error area over the receiver operating characteristic curve. The discriminating power of the digital dermoscopy analyzer plus artificial neural network was compared with histologic diagnosis. A feature selection procedure indicated that as few as 13 of the variables were sufficient to discriminate the 2 groups of lesions, and this also ensured high generalization power. The artificial neural network designed with these variables enabled a diagnostic accuracy of about 94%. In conclusion, the good diagnostic performance and high speed in reading and analyzing lesions (real time) of our method constitute an important step in the direction of automated diagnosis of pigmented skin lesions. © 2002 Wiley‐Liss, Inc.
Upregulation of matrix metalloproteinase‐9 in murine 5T33 multiple myeloma cells by interaction with bone marrow endothelial cells
Authors: Van Valckenborgh Els , Bakkus Marleen , Munaut Carine , Noël Agnes , St. Pierre Yves , Asosingh Kewal , Van Riet Ivan , Van Camp Ben , Vanderkerken Karen
Published: October 2002

MM is a B‐cell malignancy mainly characterized by monoclonal expansion of plasma cells in the BM, presence of paraprotein in serum and occurrence of osteolytic bone lesions. MMPs are a family of proteolytic enzymes that can contribute to cancer growth, invasion, angiogenesis, bone degradation and other processes important in the pathogenesis of MM. We investigated MMP‐9 production in the 5T33MM murine model. Expression of MMP‐9 protein in supernatant and cell extracts was analyzed by gelatin zymography. The in vitro, stroma‐independent variant 5T33MMvt showed no protein expression of MMP‐9 in contrast to in vivo growing MM cells, 5T33MMvv. However, when 5T33MMvt cells were injected into naive mice and isolated after tumor take (5T33MMvt‐vv), they secreted a significant amount of MMP‐9. These results were confirmed by specific staining of cytospins with an anti‐MMP‐9 antibody. The MMP‐9 production by 5T33MMvt‐vv cells disappeared when the cells were recultured in vitro. These data demonstrated that upregulation of MMP‐9 occurs in vivo and that this process is dependent on the microenvironment. Cocultures of 5T33MMvt cells with STR10 BMECs induced MMP‐9 in MM cells, as determined by both gelatin zymography and flow‐cytometric analysis. In conclusion, our results demonstrate that MMP‐9 production by MM cells is upregulated in vivo by the interaction of MM cells with BMECs. © 2002 Wiley‐Liss, Inc.
Proteasome inhibitors reconstitute the presentation of cytotoxic T‐cell epitopes in Epstein‐Barr virus–associated tumors
Authors: Gavioli Riccardo , Vertuani Simona , Masucci Maria G.
Published: October 2002

EBV‐infected cells and EBV‐associated tumors may evade CTL recognition by defective antigen processing, resulting in poor presentation of CTL epitopes. Since the proteasome is the major source of MHC class I–presented peptides, we analyzed the effect of proteasome inhibitors on the expression of surface HLA class I and the generation of EBV‐derived CTL epitopes presented by the HLA‐A2 and HLA‐A11 alleles. Treatment with covalent and reversible inhibitors of the proteasome partially reduced the total and allele‐specific expression of surface HLA class I in EBV‐carrying LCLs. HLA‐A2 expression was also decreased by treatment with leupeptin and bestatin, while HLA‐A11 expression was affected by treatment with phenanthroline. Despite their general inhibitory effect on HLA class I expression, all proteasome inhibitors tested enhanced the presentation of 2 subdominant HLA‐A2 epitopes from EBV LMP1 and LMP2, while the presentation of the immunodominant HLA‐A11‐restricted epitope from EBNA4 was inhibited by MG132 and lactacystin and increased by ZL3VS. Treatment with ZL3VS restored the presentation of endogenously expressed EBNA4 in 1 HLA‐A11‐positive BL cell line. These findings suggest that specific inhibitors of the proteasome may be used to increase the antigenicity of virus‐infected and malignant cells that are per se inefficient at generating particular CTL target epitopes. © 2002 Wiley‐Liss, Inc.
The kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: A prospective study
Authors: Grob Jean Jacques , Richard Marie Aleth , Gouvernet Johany , Avril Marie Françoise , Delaunay Michèle , Wolkenstein Pierre , Souteyrand Pierre , Bonerandi Jean Jacques , Machet Laurent , Guillaume Jean Claude , Chevrant‐Breton Jacqueline , Vilmer Catherine , Aubin François , Guillot Bernard , Beylot‐Barry Marie , Lok Catherine , Raison‐Peyron Nadia , Chemaly Philippe ,   Groupe de Cancérologie Cutanée, Société Francaise de Dermatologie, France
Published: October 2002

Primary melanoma (MM) could be a good model to test an intuitive concept: a cancer that is growing fast in its early phase is likely to have a high aggressiveness. Since MMs are visible tumors, many patients can provide information to indirectly assess the kinetics of their lesion. A prospective study was designed to assess if the kinetics of the visible growth of a primary MM, as described by the patient, could be a noninvasive prognostic marker. The ratio of MM thickness to delay between MM appearance and MM removal was used as a surrogate value for the kinetics of the MM growth. To assess the delay between MM appearance and removal, 362 patients with self‐detected invasive MM fulfilled a detailed questionnaire, which provided 2 types of estimations of this delay and thus 2 melanoma kinetics indexes (MKI and MKI*). After a median follow‐up of 4 years, univariate and multivariate analyses assessed whether relapse‐free survival was linked to MKI or MKI*. MKI was significantly predictive of relapse‐free survival (HR = 1.84 [1.51–2.25]) and relapse at 1 year (RR = 2.93 [1.84–4.69]), independently from Breslow thickness. MKI was retained in multivariate prognostic models, just after thickness and before other usual markers. MKI* was also a significant independent risk marker, although less predictive. In this model, the initial growth kinetics of a cancer reflects its aggressiveness and a high index predicts a short‐term relapse. The “subjective” data obtained from patients about their MM history, although usually neglected, can thus provide a better prognostic marker than many “objective” tests. © 2002 Wiley‐Liss, Inc.
A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false‐negative mammography
Authors: Tilanus‐Linthorst Madeleine , Verhoog Leon , Obdeijn Inge‐Marie , Bartels Karina , Menke‐Pluymers Marian , Eggermont Alexander , Klijn Jan , Meijers‐Heijboer Hanne , van der Kwast Theo , Brekelmans Cecile
Published: October 2002

Female BRCA1/2 mutation carriers develop in up to 50% breast cancer (BC) before age 50 years. We investigated whether the specific histologic features of BRCA1/2‐associated breast cancer influence imaging. We correlated the mammographic results with the histology of 34 BC in BRCA1/2 mutation carriers and 34 sporadic cancers in patients, matched for age and year of diagnosis. Mammography was significantly more frequently false‐negative in carriers than controls (62% vs. 29% p = 0.01), despite comparable tumor size (mean ⊘ 1.51 vs. 1.75) and breast density (high 41% vs. 53%). The image in carriers was significantly less as spiculated mass (6 vs. 18 p = 0.01). Cancers of BRCA1/2 mutation carriers had frequently higher mitotic counts (p < 0.0001) and prominent pushing margins around the tumor (p = 0.08) (p = 0.05 for 32 BRCA1). We also observed that prominent “pushing margins” correlated significantly with a false‐negative mammography (p = 0.005) and with a mammographic image of a smooth, not a spiculated, mass (p = 0.01). False‐negative mammography correlated independently with: BRCA1/2 mutation (p = 0.02), prominent pushing margins (p = 0.03) and high breast density (p = 0.01). MRI was carried out in 12 carriers, had 100% sensitivity and detected 5 cancers, still occult at physical examination and mammography. A BRCA1/2 mutation and high breast density at mammography contribute independently to false‐negative mammography results. In mutation carriers any mammographic mass must be regarded with suspicion. Pushing margins of the tumor partly explain these results. For early BC detection in mutation carriers additional methods like MRI may be needed. This may not be necessary in other young women with breast symptoms. © 2002 Wiley‐Liss, Inc.
Populations of the industrial world — a convergent demographic community?
Authors: Coleman D. A.
Published: October 2002

Europe's populations have emerged from a long period of demographic transition. The old demographic anciens regimes no longer exist. The end‐point of demographic transition is often assumed to be convergence to a new stable post‐transitional regime. Convergence in demographic characteristics among all European countries might be expected to follow their acquisition of common economic and social structures. Remaining differences would then merely reflect different positions on the same trajectory to a common statistical destination. However, socio‐economic convergence remains incomplete and cannot be assumed to bring uniform demographic responses in its wake. This paper measures demographic convergence in industrial societies to see if they are acquiring a common pattern. Despite some clear upper limits to demographic variables, for example fertility, in proportional terms international demographic variation remains high and is declining only slowly, if at all. Either the expectation of convergence is wrong, or we are looking for it too soon. Copyright © 2002 John Wiley & Sons, Ltd.
Absorption, disposition and metabolism of di‐isononyl phthalate (DINP) in F‐344 rats
Authors: McKee R. H. , El‐Hawari M. , Stoltz M. , Pallas F. , Lington A. W.
Published: October 2002

Di‐isononyl phthalate (DINP; CAS no. 68515‐48‐0) is a general‐purpose plasticizer for polyvinyl chloride. It produced liver and kidney effects when given to rodents at high oral doses, but there were no target organ effects in primates treated under similar conditions. To assist in understanding the basis for these species differences, the pharmacokinetic properties of DINP were evaluated in rodents following both oral and dermal administration. These studies demonstrated that the pharmacokinetic properties of DINP are similar to those of other high‐molecular‐weight phthalates. When orally administered to rodents, DINP is rapidly metabolized in the gastrointestinal tract to the corresponding monoester, absorbed and excreted, primarily in the urine. Shortly after administration, DINP is found primarily in liver and kidneys, but it does not persist or accumulate in any organ or tissue. It is very poorly absorbed from the skin, but once absorbed it behaves in the same way as the orally administered material. The results of these rodent studies contrast with data from studies involving humans or other primates, which indicate low absorption at low oral doses and much more limited total absorption at high doses. It appears that many, if not all, of the effects of DINP in rodent studies are associated with internal doses that would be difficult, if not impossible, to achieve in humans under any circumstances. Thus, the results of rodent studies may not be very useful in assessing the potential risks to humans from high‐molecular‐weight phthalates. Copyright © 2002 John Wiley & Sons, Ltd.