bluuebunny/crossref_metadata_2025 huggingface dataset:
R/qtl: QTL mapping in experimental crosses
Authors: Broman Karl W. , Wu Hao , Sen Śaunak , Churchill Gary A.
Published: April 2003

Summary: R/qtl is an extensible, interactive environment for mapping quantitative trait loci (QTLs) in experimental populations derived from inbred lines. It is implemented as an add-on package for the freely-available statistical software, R, and includes functions for estimating genetic maps, identifying genotyping errors, and performing single-QTL and two-dimensional, two-QTL genome scans by multiple methods, with the possible inclusion of covariates.

Availability: The package is freely available at http://www.biostat.jhsph.edu/~kbroman/qtl.

Contact: kbroman@jhsph.edu

* To whom correspondence should be addressed.

† Present address: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA.
The role of soil in the external corrosion of cast iron water mains in Toronto, Canada
Authors: Doyle Garry , Seica Michael V , Grabinsky Murray WF
Published: April 2003

External corrosion is a major factor contributing to the deterioration of cast iron water mains; it weakens the pipe wall, which increases the risk of failure. External corrosion is a function of the interaction between the pipeline and the soil that surrounds it. The aggressiveness of soil towards cast iron is affected by soil properties such as resistivity, pH, and the presence of sulphate reducing bacteria. Water main sections and accompanying soil samples were collected from locations across Toronto within the framework of a comprehensive research project over a 2 year period. After careful examination of the effect of each of the soil properties, it appears that soil resistivity has the largest effect on the observed maximum average pitting rate. Limitations to the practical application of the American Water Works Association soil corrosiveness scoring system are also presented. A preliminary spatial analysis of the data indicates that water mains in the district of Etobicoke have had a higher average rate of external corrosion than those in the district of Toronto. Microbiological corrosion could be an aggravating factor in the district of Etobicoke, since areas exhibiting increased levels of sulphide concentration were identified in soils that had originated from this district.Key words: water mains, external corrosion, soil properties, Toronto, cast iron, pipes.
Méthode de localisation des moraines de convergence dans une ancienne vallée glaciaire (Pyrénées, France) : conséquences sur les instabilités des moraines et reconstruction des glaciers au Würm
Authors: Fabre Richard , Texier Jean-Pierre , Clément Bernard , Lebourg Thomas
Published: April 2003

In this work, we show how it is possible to locate the thickest of till areas from the geological and geomorphological map-making of glacial formations in high mountain sites. This qualitative information is the result of a mapping methodology realized in two stages, and applied to an old glaciated Pyrenees valley, the Aspe valley. In the first stage, we show the need to draw the map of the undifferentiated glacial formations to establish the geomorphological Aspe valley map during the Würm (10 000 to 70 000 BC). This period of glaciation is correlated to the Northern Europe glacial Weichselien episode. The second stage consists in superimposing the topographic and geomorphological maps to determine the altimetric position of the lateral and convergence tills of the various glaciers. The method proposed makes it possible to obtain on a map, the position of the thickest convergence tills. The thickest of the convergence tills is verified in the field by different electrical surveys. Also, we observed that more than 50% of the landslides present in this valley are probably of Holocene age, but not reactivated at present. This can be explained by the strong variation of their mechanical characteristics compared with the slope of the side and the substratum. We show that the suggested map-making method can be applied, under certain conditions, to other glaciated valleys.Key words: Pyrenees, Würm (Weichselian age), glacial modelling, moraine, landslides.
Groundwater flow and solute transport in a laboratory-scale analogue of a decommissioned in-pit tailings management facility
Authors: West Anthony CF , Van Geel Paul J , Raven Kenneth G , Nguyen Thanh Son , Belfadhel Mahrez Ben , Flavelle Peter
Published: April 2003

A laboratory-scale analogue of an in-pit tailings management facility (TMF) was constructed using mortar sand, fluorescent-dye-containing ground silica, and filter gravel to represent fractured host rock, tailings, and a pervious surround, respectively. In a series of experiments, the performance of the analogue was observed through collection of hydraulic head, groundwater discharge, and solute concentration data. These data were found to be sufficient to validate numerical simulations of the experiments carried out using FRAC3DVS. The validation exercise indicated that adequate discretization of the tailings' periphery was critical to accurate simulation of early time solute release from the ground silica, while accurate simulation of groundwater flow and hydrodynamic dispersion adjacent to the ground silica was critical to accurate simulation of the down-gradient solute plumes. The validated model was used to predict how the analogue would have performed over its entire "contaminating lifespan." The results of the experiments and subsequent numerical modelling were used to support the argument that, assuming no dissolution of tailings solids, solute mass flux out of a decommissioned in-pit TMF would decrease asymptotically with time from a rate controlled by diffusion at the tailings' periphery towards a steady rate controlled by advection through their core.Key words: tailings, groundwater contamination, in-pit disposal, physical model, numerical model, advection-dispersion.
New consolidation equation for soilcement pile improved ground
Authors: Lorenzo Glen A , Bergado Dennes T
Published: April 2003

During the consolidation process of a soilcement pile unit cell, the excess pore pressure of the pile cannot be assumed to be zero at any given time. However, the higher coefficient of consolidation and coefficient of permeability of the soilcement pile relative to that of the surrounding clay allows its excess pore-water pressure to dissipate quickly. This subsequently creates a hydraulic gradient with the adjacent surrounding clay and allows the pore water from the latter to flow radially. While the consolidation process of the soilcement pile controls the radial drainage of the pore water into the surrounding clay, the entrance of the pore water from the surrounding clay also subsequently alters the consolidation process of the pile. A new governing equation that describes the interdependent consolidation of the pile and its surrounding clay in a typical unit cell of soilcement pile improved ground has been derived. Solutions to this governing equation corresponding to two extreme compatibility conditions of load transfer device, namely, equal stress and equal strain conditions, are presented. Moreover, the procedure to estimate the consolidation of this improved ground when it is loaded through a partially rigid load transfer device is also discussed. Finally, design charts are generated and one case history is analyzed to verify the use of this new governing consolidation equation.Key words: soilcement pile, consolidation, compressibility, ground improvement, unit cell.
An anisotropic elastoplastic model for soft clays
Authors: Wheeler Simon J , Näätänen Anu , Karstunen Minna , Lojander Matti
Published: April 2003

An anisotropic elastoplastic model for soft clays is presented. Experimental data from multistage drained triaxial stress path tests on Otaniemi clay from Finland provide support for the proposed shape of the yield curve and for the proposed relationship describing the change of yield curve inclination with plastic straining. Procedures are proposed for determining the initial inclination of the yield curve and the values of the two additional soil constants within the model. Comparisons of model simulations with experimental data demonstrate significant improvements in the performance of the new model over the Modified Cam Clay model. The remaining discrepancies are mainly attributable to the important role of destructuration in the sensitive Otaniemi clay.Key words: anisotropy, constitutive relations, elastoplasticity, laboratory tests, rotational hardening, soft clays.
Effect of seepage forces on tunnel face stability
Authors: Lee In-Mo , Nam Seok-Woo , Ahn Jae-Hun
Published: April 2003

In this study, two factors are simultaneously considered for assessing tunnel face stability. The first is the effective stress acting on the tunnel face calculated by upper bound solution, and the other is the seepage force calculated by numerical analysis under the condition of steady-state groundwater flow. The seepage forces calculated by numerical analysis are compared with the results of a model test. The upper bound solution taking into consideration the seepage force acting on the tunnel face, shows that the minimum support pressure for the face stability is equal to the sum of the effective support pressure that is obtained from the upper bound solution based on effective stress and the seepage pressure acting on the tunnel face. It was found that the average seepage pressure acting on the tunnel face is proportional to the hydrostatic pressure at the same elevation, and the magnitude is about 22% of the hydrostatic pressure for the drainage type tunnel and about 28% for the waterproof type tunnel. The seepage forces obtained from the results of a model test showed similar trends as those calculated by numerical analysis.Key words: face stability, upper bound solution, seepage force, model test.
A limit equilibrium solution for bearing capacity of strip foundations on sand
Authors: Silvestri Vincenzo
Published: April 2003

A limit equilibrium analysis is used in this paper to obtain the bearing capacity of a strip foundation on sand. Bearing capacity factors Nq and Nγ are determined for a practical range of friction angles, using a minimization procedure. The dilatancy angle Ψ of the sand coupled with the apparent friction angle ϕ allows the use of a modified friction angle ϕ*, which is in turn employed in the analysis. Comparisons with previous published data indicate that the proposed analysis gives adequate results. It is also shown that consideration of a dilatancy angle Ψ < ϕ leads to a bearing capacity value that is lower than that obtained for the case with Ψ = ϕ.Key words: limit equilibrium, bearing capacity, sand, dilatancy, strip footing, Nq and Nγ factors.
ON THE GEOMETRY OF THE CHARACTERISTIC CLASS OF A STAR PRODUCT ON A SYMPLECTIC MANIFOLD
Authors: BIELIAVSKY PIERRE , BONNEAU PHILIPPE
Published: April 2003

The characteristic class of a star product on a symplectic manifold appears as the class of a deformation of a given symplectic connection, as described by Fedosov. In contrast, one usually thinks of the characteristic class of a star product as the class of a deformation of the Poisson structure (as in Kontsevich's work). In this paper, we present, in the symplectic framework, a natural procedure for constructing a star product by directly quantizing a deformation of the symplectic structure. Basically, in Fedosov's recursive formula for the star product with zero characteristic class, we replace the symplectic structure by one of its formal deformations in the parameter ℏ. We then show that every equivalence class of star products contains such an element. Moreover, within a given class, equivalences between such star products are realized by formal one-parameter families of diffeomorphisms, as produced by Moser's argument.
ODOR MIXTURES AND CHEMOSENSORY ADAPTATION IN GAS SENSOR ARRAYS
Authors: GUTIERREZ-OSUNA RICARDO , POWAR NILESH U.
Published: April 2003

Inspired by the process of olfactory adaptation in biological olfactory systems, this article presents two algorithms that allow a chemical sensor array to reduce its sensitivity to odors previously detected in the environment. The first algorithm is based on a committee machine of linear discriminant functions that operate on multiple subsets of the overall sensory input. Adaptation occurs by depressing the voting strength of discriminant functions that display higher sensitivity to previously detected odors. The second algorithm is based on a topology-preserving linear projection derived from Fisher's class separability criteria. In this case, the process of adaptation is implemented through a reformulation of the between-to-within-class scatter eigenvalue problem. The proposed algorithms are validated on two datasets of binary and ternary mixtures of organic solvents using an array of temperature-modulated metal-oxide chemoresistors.
AGENT-BASED COMMUNICATION FOR DISTRIBUTED WORKFLOW MANAGEMENT USING JINI TECHNOLOGIES
Authors: BRIAN BLAKE M.
Published: April 2003

Agent communication has developed widely over the past decade for various types of multiple agent environments. Originally, most of this research surrounded simulation systems and inference systems. Subsequently, agents are expected to adapt to, dynamically create, and understand evolving conversation policies. This concept of agent communication is not completely necessary in some domains. One such domain is that of distributed workflow management with implications into Electronic Commerce. In this domain, agents are "middle-agents" that represent the distributed components that implement each individual workflow step. By representing the component-based services of each step, multiple distributed agents can essentially manage a workflow or supply chain that spans several online businesses (B2B). The WARP (Workflow-Automation through Agent-Based Reflective Processes) architecture is a multi-agent architecture developed to support distributed workflow management environments where distributed components are used to implement each of the workflow steps This paper describes an object-oriented workflow ontology for this distributed workflow management domain. There is also a software engineering process for integrating new component-based services into this ontology. Furthermore, the interaction protocol and supporting implementation based on the Knowledge Query and Manipulation Language (KQML) are presented. This agent communication architecture is implemented using Sun MicroSystems' Java and Jini technologies.
IGDA. 2: Interviewing the patient
Authors:   IGDA Workgroup, WPA
Published: April 2003

An appropriate setting for the psychiatric interview should be selected or arranged within the circumstances available. It should be as comfortable as possible for both patient and interviewer, protect privacy, and minimise external distractions.
Is academic psychiatry for sale?
Authors: Healy David , Thase Michael E.
Published: April 2003

The influence of the pharmaceutical industry on academic medicine is pervasive. Almost 90% of authors published in the Journal of the American Medical Associatio. have received research funding from, or acted as a consultant for, a drug company. Rising to this challenge, editors of medical journals have agreed strict rules on reporting sponsorship and conflicts of interest. Academic psychiatry is not exempt from the influence of industry. The relationship between drug companies and academic psychiatry is currently very close. But is this a problem? On the one hand, links with the pharmaceutical industry may be considered to compromise the independence of researchers and possibly discredit their published work. On the other hand the relationship may be seen as productive and mutually beneficial – particularly in an era of limited funds for research. These issues are discussed in this month's debate by Dr David Healy, Director of the North Wales Psychiatric Service, who is a well-known commentator on the pharmaceutical industry, and Dr Michael Thase, Professor of Psychiatry at the University of Pittsburgh School of Medicine and the author of a meta-analysis on the effectiveness of venlafaxine published in this Journal in 2001.
Stability of Cefepime Hydrochloride in AutoDose Infusion System Bags
Authors: Trissel Lawrence A , Xu Quanyun A
Published: April 2003

OBJECTIVE:

To evaluate the physical and chemical stability of cefepime (as the hydrochloride) 1 g/100 mL and 4 g/100 mL admixed in NaCl 0.9% injection and packaged in AutoDose Infusion System bags.

DESIGN:

Triplicate test samples of cefepime hydrochloride in NaCl 0.9% injection were packaged in ethylene vinyl acetate plastic containers, AutoDose bags, designed for use in the AutoDose Infusion System. Samples were stored protected from light and evaluated at appropriate intervals for up to 7 days at room temperature of approximately 23 °C and 30 days under refrigeration at 4 °C. Physical stability was assessed using turbidimetric and particulate measurement, as well as visual inspection. Chemical stability was assessed by HPLC.

RESULTS:

All of the admixtures were initially clear and light yellow when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially but increased over time, eventually becoming a yellow or orange precipitate. The higher concentration precipitated earlier; refrigeration slowed precipitation for both test concentrations. HPLC analysis found that the 1-g/100 mL concentration maintained adequate stability for 2 days at 23 °C and up to 30 days at 4 °C. The 4-g/100 mL concentration maintained adequate stability for 1 day at room temperature and 7 days under refrigeration; however, unacceptable drug loss and precipitation developed after those time points.

CONCLUSIONS:

Cefepime hydrochloride exhibited physical and chemical stability consistent with previous stability studies. The AutoDose Infusion System bags were not found to affect adversely the physical and chemical stability of this drug.
Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction
Authors: Sipe Brooke E , Jones Ronald J , Bokhart Gordon H
Published: April 2003

OBJECTIVE:

To report rhabdomyolysis (RML) causing third-degree atrioventricular block secondary to a possible interaction between atorvastatin, esomeprazole, and clarithromycin.

CASE SUMMARY:

A 51-year-old white woman presented to the emergency department with severe weakness, near syncope, shortness of breath, and chest pain. On admission, her electrocardiogram demonstrated bradycardia (40 beats/min) and third-degree heart block. A creatine kinase (CK) level was >7000 U/L. Her medication history was significant for long-term use of atorvastatin (>1 y), a 6-week history of esomeprazole use, and three 500-mg doses of clarithromycin just prior to admission. Her symptoms of weakness, shortness of breath, and chest pain coincided with starting the esomeprazole. During her hospitalization, the woman required pacemaker placement and her CK continued to rise to >40 000 U/L. Screening for other causes of RML, such as thyrotoxicosis, infection, and immune or hepatic diseases, was negative. She gradually improved over a 26-day hospitalization.

DISCUSSION:

This is a case of RML resulting in third-degree atrioventricular blockade. An objective causality assessment of the adverse reaction via the Naranjo probability scale revealed a probable association with atorvastatin and a possible association with esomeprazole and clarithromycin. The pharmacokinetic profiles of these agents suggest that a possible contribution to this reaction was P-glycoprotein (PGP) inhibition by esomeprazole altering atorvastatin's normally significant first-pass clearance.

CONCLUSIONS:

PGP drug interactions with atorvastatin and other hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may be associated with unreported risks for RML. Further investigation into PGP impact on HMG-CoA appears warranted.
Communication of BRCA1 and BRCA2 results to at‐risk relatives: A cancer risk assessment program's experience
Authors: Costalas Josephine Wagner , Itzen Mark , Malick John , Babb James S. , Bove Betsy , Godwin Andrew K. , Daly Mary B.
Published: April 2003

We describe results from a survey designed to assess patterns of communication within families shortly after an individual receives results of BRCA1 and BRCA2 mutation carrier status. Shortly after disclosure of BRCA1 and BRCA2 genetic test results, the proband was contacted by phone to administer the post disclosure survey. Questions asked included whether they had shared their results with their siblings or adult children, if there were difficulties in communicating the test results, and if there was any distress associated with the sharing of results. A total of 162 women who have received results from BRCA1 and BRCA2 genetic testing participated in the survey. The probands shared their results more often with their female than their male relatives (P < 0.001). Probands who had tested positive for a mutation in the BRCA1 or BRCA2 gene shared their results more often with their relatives than did probands who were not carriers (P = 0.002). Probands reported more often that their siblings rather than their adult children had difficulties understanding the results (P = 0.001). The probands who were carriers more often reported having difficulties explaining their results to their relatives (P < 0.001) and their relatives were upset on hearing the result more often than were the relatives of probands who were not carriers (P < 0.001). The probands who were carriers reported more often that they were upset explaining their results to their relatives than did the probands who were not carriers (P < 0.001). Individuals are disclosing their test results to their relatives. Probands who are BRCA1‐ or BRCA2‐positive are more likely to experience difficulty and distress with the communication of their test results to family members. © 2002 Wiley‐Liss, Inc.
Duty to warn at‐risk relatives for genetic disease: Genetic counselors' clinical experience
Authors: Dugan R. Beth , Wiesner Georgia L. , Juengst Eric T. , O'Riordan Maryann , Matthews Anne L. , Robin Nathaniel H.
Published: April 2003

When a patient refuses to inform relatives of their risk for genetic disease, the genetic healthcare professional is faced with conflicting ethical obligations. On one side of the issue is the obligation to respect and protect patients' right to privacy. On the other side is the obligation to prevent harm and promote the welfare of the family members, which suggests a responsibility to warn at‐risk relatives, even without the patient's consent. In an effort to examine the actual clinical impact of this issue, we conducted a pilot study that explored genetic counselors' experience with this conflict. A survey was developed and made available to members of the National Society of Genetic Counselors. Questions were either multiple‐choice responses or open‐ended. Almost half of respondents (119/259; 46%) had had a patient refuse to notify an at‐risk relative. The most commonly cited reasons for refusal were estranged family relationships, altering family dynamics, insurance discrimination, and employment discrimination, respectively. Of these 119 counselors, 24 (21%) reported that they seriously considered warning the at‐risk relatives without patient consent, and one actually did disclose. Three factors consistently made the counselors less likely to disclose: their patient's potential emotional reaction, the relationship between the relative and patient, and the chance that the relative could be aware of the disease by another means. These results suggest that while the conflict is often encountered in clinical practice, it is rare that the situation remains unresolved to the extent that genetic counselors actually consider warning at‐risk relatives. However, when the situation was encountered, the counselors in this study reported a lower rate of disclosure without consent than would have been anticipated based on previous studies that used hypothetical situations. It may be that counselors do not recognize a duty to warn at‐risk relatives as integral to their role and professional obligations. © 2003 Wiley‐Liss, Inc.
Cover Picture: Cocrystallization with Acetylene: Molecular Complexes with Acetone and Dimethyl Sulfoxide (Angew. Chem. Int. Ed. 17/2003)
Authors: Boese Roland , Kirchner Michael T. , Billups W. Edward , Norman Lewis R.
Published: April 2003

By in situ crystallization under pressure in a capillary, two different phases of acetylene complexes were grown simultaneously. The crystals gave the superimposed diffraction patterns shown in the background. From the reflections of the 1:1 phase (red) two cell parameters can be determined directly. In the reflections of the 1:2 phase (white) another reciprocal lattice is visible on viewing the picture from the side. For more information see the article by R. Boese et al. on page 1961 ff.
The effects of shore‐based diamond‐diving on intertidal and subtidal biological communities and rock lobsters in southern Namibia
Authors: Pulfrich Andrea , Parkins Colleen A. , Branch George M.
Published: April 2003

Divers mine shallow‐water diamonds on the west coasts of South Africa and Namibia. In the process they cut kelp, suck up gravel that is sorted on the shore and then deposited intertidally, and uncover and overturn subtidal boulders.

The impacts of these divers on intertidal and subtidal reefs, and on the population structure of the commercially important rock lobster Jasus lalandii, were monitored for 5 years near Lüderitz in southern Namibia. Sampling was undertaken at unmined reference (control) sites and at sites mined at various times in the past. Percentage cover and densities of benthic organisms were recorded, and the abundance, length‐frequencies and sex ratios of rock lobsters determined.

High natural variability in benthic community structure made it difficult to distinguish mining impacts even a short time after mining had ceased. Nevertheless, mining reduced the species diversity and abundance of both intertidal and subtidal communities. Recovery did, however, occur within 2 years. During, or immediately after mining, the intertidal community became characterized by the near disappearance of grazers, proliferation of fast‐growing, opportunistic foliose algae and decreased cover of filter‐feeders. Subsequently, grazers increased, curtailing the algae. In contrast, mining reduced subtidal algal cover. Kelp was cut to facilitate mining, foliose algae were removed and smothered as rocks were overturned, and reef‐building filter‐feeders diminished.

The abundance and population structure of rock lobsters appeared to be largely determined by environmental conditions and habitat suitability. Their abundance and catch per unit effort were more often higher at reference sites and recently mined sites than at sites mined > 5 years previously. Sex ratios and mean sizes of rock lobsters were not statistically affected by mining. Mining does alter the biological and physical characteristics of the habitat, and in the process, it may temporarily increase the availability of suitable rock‐lobster habitats. No negative impacts of shore‐based diamond‐diving on rock lobsters were detected.

Copyright © 2002 John Wiley & Sons, Ltd.
Environmental changes in man‐made coastal dune pools since 1850 as indicated by sedimentary and epiphytic diatom assemblages (Belgium)
Authors: Denys Luc
Published: April 2003

Diatom assemblages of man‐made coastal dune wetlands between Blankenberge and Heist (Belgium), dating from 1852 to 1929 and sampled from herbarium specimens of macrophytes, were compared with more recent samples collected in the remaining calcareous dune marshes and pools in this area.

Overall, nutrient conditions inferred from the reference assemblages were fairly eutrophic for phosphorus. Only a minority of the historical assemblages pointed to presumably nitrogen‐limited conditions.

Significant alterations in general assemblage composition were observed, including a marked decline of epiphytic species, and a decrease in the compositional variation in sediment diatom assemblages. These changes can be attributed mainly to an increased availability of nutrients and degradable organic matter since the mid 1970s. No changes in the salinity range seem to have occurred, suggesting fairly stable hydrological conditions.

Possible causes for eutrophication include increased atmospheric deposition of nutrients, but also more site‐related phenomena such as guanotrophication, angling and, perhaps, effects of nature management on soil–nutrient cycling. Their relative importance needs to be established and further monitoring is necessary.

Measures are required to reduce nutrient levels of both permanently and periodically inundated sites and to promote small‐scale habitat differentiation. Due to physical constraints, the latter will be possible only by mimicking the processes that act upon more natural dune systems in management practice.

Copyright © 2003 John Wiley & Sons, Ltd.
Mice with neonatally induced inactivation of the vascular cell adhesion molecule‐1 fail to control the parasite in Toxoplasma encephalitis
Authors: Deckert Martina , Lütjen Sonja , Leuker Christoph E. , Kwok Lai‐Yu , Strack Andreas , Müller Werner , Wagner Norbert , Schlüter Dirk
Published: April 2003

Under various inflammatory conditions, cell adhesion molecules are up‐regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)‐1 in Toxoplasma encephalitis (TE) was addressed using VCAMflox/flox MxCre mice. Neonatal inactivation of the VCAM‐1 gene resulted in a lack of induction of VCAM‐1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM‐1 on choroid plexus epithelial cells and the ependymawas unaffected; in these animals, resistance to T. gondii was abolished, and VCAMflox/flox MxCre mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti‐T. gondii‐specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T. gondii‐specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM‐1‐mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM‐1‐mediated homing across cerebral blood vessels.
Proteoglycans are potent modulators of the biological responses of eosinophils to chemokines
Authors: Culley Fiona J. , Fadlon Emma J. , Kirchem Antje , Williams Timothy J. , Jose Peter J. , Pease James E.
Published: April 2003

Chemokines play critical roles in governing the recruitment and activation of eosinophils at sites of allergic inflammation, particularly the asthmatic lung. However, we know little of how chemokine function is regulated post‐translationally. Proteoglycans, consisting of a core protein and glycosaminoglycan (GAG) side chains, are cell surface molecules and components of the extracellularmatrix that are able to bind chemokines, whilst heparin is a GAG with therapeutic value in asthma. We examined whether soluble GAG could alter the actions of chemokines in assays of eosinophil activation. Heparin inhibited intracellular calcium flux, respiratory burst and chemotactic responses of eosinophils to CCL11, but not to the chemoattractant C5a, and inhibited binding of CCL11 to CCR3. Heparin also inhibited eosinophil stimulation by CCL11, CCL24, CCL7, CCL13 and CCL5 to differing degrees, which broadly correlated with their relative affinities for heparin. Heparan sulfate and dermatan sulfate, but not chondroitin sulfate, also inhibited the actions of CCL11 and CCL13 in assays of cellular shape change and chemotaxis. Following treatment with the sulfation inhibitor chlorate or proteoglycanases, no inhibition of CCL11‐induced activity was observed using either eosinophils or a CCR3‐expressing transfectant cell line. This suggests that cell surface proteoglycans are not necessary for signaling via CCR3. However, the GAG context in which chemokines are expressed is likely to represent an important level of regulation of allergic inflammation.
Comparison of FcϵRI‐ and FcγRI‐mediated degranulation and TNF‐α synthesis in human mast cells: selective utilization of phosphatidylinositol‐3‐kinase for FcγRI‐induced degranulation
Authors: Okayama Yoshimichi , Tkaczyk Christine , Metcalfe Dean D. , Gilfillan Alasdair M.
Published: April 2003

We have demonstrated that CD34+ IFN‐γ‐treated human mast cells (HuMC) express functional FcγRI and that aggregation of these receptors leads to mediator release. As the signaling pathways linking FcγRI aggregation to mediator release are unknown, we examined FcγRI‐dependent activation of specific signal transduction molecules and determined the relative involvement of these events in HuMC degranulation and TNF‐α production following both FcγRI and FcϵRI aggregation. FcγRI aggregation resulted in the phosphorylation/activation of srckinases and p72syk and subsequent tyrosine phosphorylation of multiple substrates. Inhibitor studies revealed that these responses were required for degranulation and TNF‐α synthesis. Both FcγRI and FcϵRI aggregation also activated the MAP kinases ERK 1/2, JNK and p38 and this was necessary for TNF‐α synthesis, but not degranulation for both receptors. Thus, signalingevents in HuMC following aggregation of FcγRI were generally similar to those observed following FcϵRI aggregation. The one exception was that, although phosphatidylinositol‐3‐kinase was activated after both FcϵRI and FcγRI aggregation, only the FcγRI appeared to require this molecule for degranulation.
Tumor rejection by gene transfer of the MHC class II transactivator in murine mammary adenocarcinoma cells
Authors: Meazza Raffaella , Comes Alberto , Orengo Anna M. , Ferrini Silvano , Accolla Roberto S.
Published: April 2003

The murine mammary adenocarcinoma cell line TS/A is a highly malignant MHC class II‐negative tumor. We show that transfection of TS/A cells with the MHC class II transactivator CIITA renders them MHC class II‐positive and highly immunogenic in vivo. These cells were fully rejected by 51% of syngeneic recipients and had a significantly lower growth rate in the remaining 49% of animals. This directly correlated to the amount of MHC class II molecules expressed in the transfected tumor. Tumor rejecting animals were protected against rechallenge with the parental TS/A tumor. The rejection required CD4+ and CD8+ T cells. CD4+ T cells were fundamental in the priming phase of the antitumor response. CTL‐specific for a peptide of the envelope gp70 of an endogenous ecotropic retrovirus were identified and explained the specificity of the effector mechanism of rejection against the TS/A and the antigenically related C26 carcinoma cells but not against the unrelated gp70‐negative syngeneic fibrosarcoma F1F cells. This is the first example of successful tumor vaccination by genetic transfer of CIITA. These results open the way to a possible use of CIITA for increasing both the inducing and the effector phase of the antitumor immune response.
A role for antibodies in the generation of memory antifungal immunity
Authors: Montagnoli Claudia , Bozza Silvia , Bacci Angela , Gaziano Roberta , Mosci Paolo , Morschhäuser Joachim , Pitzurra Lucia , Kopf Manfred , Cutler Jim , Romani Luigina
Published: April 2003

Protective immunity to Candida albicans and Aspergillus fumigatus is mediated by antigen‐specific Th1 cells. To define the role of B cells and antibodies in the generation ofantifungal immune resistance, B cell‐deficient (μMT) mice were assessed for immune resistance to primary and secondary infections with both fungi. The results showed that, although passive administration of antibodies increased the fungal clearance, the innate and Th1‐mediated resistance to the primary and secondary infections were both heightened in μMT mice with candidiasis and aspergillosis. However, although capable of efficiently restricting the fungal growth, μMT mice did not survive the re‐infection with C. albicans, and this was concurrent with the failure to generate IL‐10‐producing dendritic cells and regulatory CD4+CD25+ T cells. Antifungal opsonizing antibodies restored IL‐10 production by dendritic cells from μMT mice, a finding suggesting that the availability of opsonizing antibodies may condition the nature of the dendritic cell interaction with fungi, possibly impacting on the development of long‐lasting antifungal immunity.
Catalytic Aziridination of Styrene with Copper Complexes of Substituted 3,7‐Diazabicyclo[3.3.1]nonanones
Authors: Comba Peter , Merz Michael , Pritzkow Hans
Published: April 2003

The copper(II) complexes of five bispidine‐type ligands {3,7‐diazabicyclo[3.3.1]nonanone; three tetradentate ligands with 2‐pyridyl (L1), 6‐methyl‐2‐pyridyl (L2) or 2‐imidazolyl‐3‐methyl (L3) substituents in 2,4‐positions; two pentadentate derivatives of L1 with an additional 2‐methylpyridine substituent at N3 (L4) or N7 (L5)} have, with one co‐ligand (Cl−), a ligand‐enforced square pyramidal (L1,2,3) or octahedral (L4,5) geometry. The main structural properties of three of the five [Cu(L)(Cl)]+ complexes (L1,2,3) are very similar, with Cu−N3 < Cu−N7 and Cu−Cl ≈︁ 2.25 Å (trans to N3); with L2 Cu−N3 ≈︁ Cu−N7 and Cu−Cl = 2.22 Å (trans to N7); with L5 Cu−N3 < Cu−N7 and Cu−Cl = 2.72 Å (trans to N7). These structural patterns lead to considerable differences in ligand field and electrochemical properties (range of E° of approx. 500mV), and the reactivities of the copper(II) complexes as aziridination catalysts (styrene, PhINTs, CH3CN) are strikingly different. While the complex with L2 is very efficient, the activities of those with L1 and L3 are reduced to approx. 50% and 30%, respectively, and those with L4 and L5 are inactive. The fact that the maximum TON (maximum turnover number) of CuIIL2 (19) is much smaller than the maximum TON of CuIL2 (47) suggests that in the active form the catalysts are in the CuI oxidation state, and that the differences in reduction potentials are of major importance for catalysis. The result that CuL4,5 have no activity in the CuII state and only a small activity in the reduced form indicates that, apart from the reduction potentials, steric effects might also be of importance. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Growth Process, Stability of GaP Nanocrystals and Formation of Ga3P Nanocrystals under Solvothermal Conditions in Benzene
Authors: Gao Shanmin , Lu Jun , Zhao Yan , Chen Nan , Xie Yi
Published: April 2003

The growth process, stability of GaP nanocrystals and the formation of Ga3P nanocrystals under solvothermal conditions were investigated. At moderate reaction times and temperature, the growth process is mainly in accordance with the Ostwald ripening mechanism, which is the dissolving of the smaller GaP crystallites and growth into larger ones. However, GaP nanocrystallites become unstable under increasing reaction temperatures or prolonged reaction times. EDAX and XRD were used to identify the new Ga3P phase. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Influence of Incorporated Lipophilic Particles on Ion Fluxes Through Polymeric Ion‐Selective Membranes
Authors: Vigassy Tamás , Gyurcsányi Robert E. , Pretsch Ernö
Published: April 2003

The incorporation of lipophilic particles into the sensing membrane of ion‐selective electrodes (ISEs) can strongly influence the uptake of ions from the sample. The apparent super‐Nernstian response of ISEs caused by a strong flux of primary ions from the sample to the inner solution can be suppressed completely. This opens up new possibilities of improving the ruggedness of trace‐level measurements.
Potentiometric Study of Urease Kinetics over pH 5.36–8.21
Authors: Krajewska Barbara , Chudy Michal , Drozdek Marek , Brzózka Zbigniew
Published: April 2003

To meet the demand for a convenient method of urease assay we present the potentiometric measurement of urease activity with use of an ammonium ion‐selective electrode. The membrane of the electrode was plasticized poly(vinyl chloride) containing physically immobilized nonactine as an NH4+‐sensitive ionophore and a lipophilic salt as an anionic additive. The calibration in buffers covering pH 5.36–9.97 showed that the electrode had a Nernstian response at pH <9.17 down to about 0.06 mM NH4+ and that for each buffer the detection limit grew with an increase in pH, concentration and the presence of Na2EDTA. The response time of the electrode was 15 s. In the study of urease kinetics performed with use of the electrode over pH 5.36–8.21 we have shown that the Michaelis constant of the enzyme does not significantly change with pH and that the maximum reaction rate‐pH profile, unlike those hitherto reported, has two maxima located at a short distance of 0.7 pH unit (7.2 and 6.5). Such a profile may pave the way for a new interpretation of the acid‐base mechanism of urease action. The potentiometric method presented can be helpful in screening for urease inhibitors, the substances of importance in therapies of diseases induced by ureolytic bacteria and in agriculture for proper nitrogen management in soil.
Determination of Labile Chromium in Water Samples by Catalytic Adsorptive Stripping Voltammetry in On‐Line System
Authors: Grabarczyk Malgorzata , Korolczuk Mieczyslaw
Published: April 2003

A sensitive and selective on‐line voltammetric procedure for determination of traces of labile chromium is presented. The pulsed potential accumulation was proposed for the minimization of interferences of surface active substances and foreign ions. The calibration plot was linear from 7×10−10 mol L−1 to 3×10−8 mol L−1 for an accumulation time of 60 s. The relative standard deviation was 4.7% (n=5) for a chromium concentration of 1.5×10−8 mol L−1. The detection limit estimated from (3 σ) for an accumulation time of 60 s was about 2×10−10 mol L−1. The method was applied for the determination of labile chromium in tap and river water samples.
The Electrooxidation of Halogeno‐Anilines at Microelectrodes in Acetonitrile Solution
Authors: Pusztai Szabolcs , Dankházi Tibor , Farsang George
Published: April 2003

The electrochemical oxidation of 4‐chloro‐, 2,4‐dichloro‐, 2,4,6‐trichloro‐anilines and 4‐bromo‐, 2,4‐dibromo‐, 2,4,6‐tribromo‐anilines and 4‐iodo‐aniline were investigated in unbuffered acetonitrile solution. The main reaction at the electrooxidation of these compounds is the dimerization which is accompanied by release of the p‐substituent halide and formation of protons. To complete the so far achieved results by the apparent electron exchange number (napp) determination in the voltammetric time scale have been attempted. These measurements were carried out with the aim, to have a clearer picture on the napp influencing role of the following complicating factors: The rejected halogenides in MeCN solvent at lower potential values as the substrates can be oxidized to the corresponding halogens, and these halogens except the iodine substitute the substrate which takes place even in the voltammetric time scale by increasing the napp value characteristic for the dimerization only. The measurable napp values are influenced by the protons produced at the oxidation as well, in the opposite direction. The explanation for the latter is, that the solvent is aprotic, therefore the differently basic primary amino groups of the diffusing substrate molecules binding partly the protons and in this way voltammetrically inactive substrate species are formed. This reaction is a typical equilibrium type and this inactivation effect decrease the measurable napp value. This effect depends on the quality and number of halogene substituent at a given substrate because these affect the protonation constant of the substrate. Therefore the protonation constants of the substrates had to be determined. In the knowledge of these quantitative data the explanation of the trends in the napp values measured in the voltammetric time scale is attempted. The mechanistic study of the dimerization reaction of these substrates is in progress in our laboratory.
Micellar electrokinetic chromatography estimation of size and composition of procyanidins after thiolysis with cysteine
Authors: Herrero‐Martínez José M. , Ràfols Clara , Rosés Martí , Bosch Elisabeth , Lozano Carles , Torres Josep L.
Published: April 2003

This paper describes the characterization of procyanidin mixtures by acid depolymerization in the presence of cysteine (thiolysis with cysteine) and micellar electrokinetic chromatography (MEKC). Reversed‐phase liquid chromatography (RP‐HPLC) and MEKC were investigated for the separation of the major components of the depolymerized mixtures (catechins and their cysteinyl derivatives). The solutes could only be effectively separated using MEKC. Two background electrolytes (BGEs) are recommended: (i) 50 mM phosphate at pH 7, containing 40 mM sodium cholate (SC) and 10 mM sodium dodecyl sulfate (SDS); (ii) a BGE with the same composition but containing only 50 mM SDS. The MEKC procedures here reported, are cheap, reliable and fast, and their potential in the determination of the size and composition in procyanidin mixtures has been shown. The proposed MEKC methods were validated by comparison with our intralaboratory reference RP‐HPLC method using cysteamine as thiol donor.
Application of capillary zone electrophoresis in the separation and determination of the principal gum opium alkaloids
Authors: Reddy Mudiam Mohanakrishna , Suresh Velayudhan , Jayashanker Gurumurthy , Rao Beedu Sashidhar , Sarin Rajendra Kumar
Published: April 2003

We describe the use of capillary zone electrophoresis (CZE) for the qualitative and quantitative determination of major alkaloids (i.e., thebaine, codeine, morphine, papavarine and narcotine) in gum opium involving the analysis of alkaloids without derivatization or purification. Three extractions with 2.5% w/v aqueous acetic acid quantitatively extracted major alkaloids. The separation was carried out by CZE using a 7:3 mixture of methanol and sodium acetate (100 mM, pH 3.1) at a potential of 15 kV, with UV detection at 224 nm. Spiking of pure reference alkaloid standards in the opium extract was used for peak identification. The influences of buffer composition, pH and voltage on the separation of alkaloids were studied. The detection limit of each alkaloid dissolved in methanol was found to be 850 ng/mL (morphine), 450 ng/mL (thebaine), 500 ng/mL (codeine), 550 ng/mL (papaverine), and 500 ng/mL (narcotine) at an injection pressure of 300 mbar (injection volume, 4 nL) with a signal‐to‐noise ratio of 3:1. The external standard method was used for the quantification of alkaloids. The calibration plot was based on linear regression analysis. The relative standard deviation (RSD) for peak area and migration time was in the range of 1.03–3.56% and 0.34–0.69%, respectively. Percentage compositions (g%) of opium alkaloids in five gum opium samples were found to be in the range of 14.45–15.95 (morphine), 2.0–3.45 (codeine), 1.32–2.73 (thebaine), 0.92–2.37 (papavarine), and 3.85–5.77 (narcotine). The method developed is suitable for the routine analysis of major gum opium alkaloids in samples of forensic importance.