bluuebunny/crossref_metadata_2025 huggingface dataset:
A high pressure matrix‐assisted laser desorption/ionization Fourier transform mass spectrometry ion source for thermal stabilization of labile biomolecules
Authors: O'Connor Peter B. , Costello Catherine E.
Published: August 2002

A high pressure matrix‐assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry (FTMS) ion source was designed and tested. With this design, pressure is pulsed to an estimated 1–10 mbar in the region of the MALDI sample during desorption with the result of significantly decreased fragmentation compared to similar systems operating with pressures of <0.1 mbar. The thermal stabilization of vibrationally excited ions under these conditions is shown with small peptides desorbed from the ‘hot’ matrix α‐cyano‐4‐hydroxycinnamic acid, and with the highly labile oxidized β‐chain of insulin. Fragile gangliosides with several sialic acid residues are desorbed under high pressure and remain intact without the typical losses of sialic acid, and a protein standard, ubiquitin (8565.64 Da), is desorbed with minimal dehydration. Under high pressure collisional cooling conditions, non‐covalent matrix adduction to the molecular ions becomes prominent, but with the trapped ions in an FT mass spectrometer, the ions can be mildly activated to detach the matrix adducts. The new source, additionally, generates significant levels of the multiply charged ions which are commonly seen in MALDI‐TOFMS, but are rarely observed in MALDI‐FTMS. This effect is more likely due to the elimination of a mass filtering effect in the previous FTMS ion source than to collisional cooling of the ions. Copyright © 2001 John Wiley & Sons, Ltd.
Mass‐directed fractionation and isolation of pharmaceutical compounds by packed‐column supercritical fluid chromatography/mass spectrometry
Authors: Wang Tao , Barber Michael , Hardt Ingo , Kassel Daniel B.
Published: August 2002

An automated packed‐column semi‐preparative supercritical fluid chromatography/mass spectrometry (SFC/MS) system incorporating mass‐directed fraction collection has been designed and implemented as an alternative to preparative HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmaceutical compounds. The system incorporates a single quadrupole mass spectrometer and a supercritical fluid chromatograph. Separations were achieved using a binary solvent system consisting of carbon dioxide and methanol. Purification of SFC‐separated compounds was achieved incorporating mass‐directed fraction collection, enabling selective isolation of the target molecular weight compound and eliminating the collection of undesired compounds (e.g., by‐products, excess starting materials, etc.). Cross contamination between fractions and recoveries of the system were investigated. Mass spectrometer ionization with basic mobile additives is discussed, and examples of preparative SFC/MS chiral separations are presented. Early experiences suggest SFC will be a powerful and complementary technique to HPLC for the purification of pharmaceutical compounds. Copyright © 2001 John Wiley & Sons, Ltd.
Hydroxyl radical probe of the surface of lysozyme by synchrotron radiolysis and mass spectrometry
Authors: Maleknia Simin D. , Kiselar Janna G. , Downard Kevin M.
Published: August 2002

A new approach is reported that combines synchrotron radiolysis and mass spectrometry to probe the surface of proteins. Hydroxyl radicals produced upon the radiolysis of protein solutions with synchrotron light for several milliseconds result in the reaction of amino acid side chains. This results in the formation of stable oxidation products where the level of oxidation at the reactive residues is influenced by the accessibility of their side chains to the bulk solvent. The aromatic and sulfur‐containing residues have been found to react preferentially in accord with previous peptide studies. The sites of oxidation have been determined by tandem mass spectrometry. The rate of oxidation at these reactive markers has been measured for each of the proteolytic peptides as a function of exposure time based on the relative proportion of modified and unmodified peptide ions detected by mass spectrometry. Oxidation rates have been found to correlate closely with a theoretical measure of the accessibility of residue side chains to the bulk solvent in the native protein structure. The synchrotron‐based approach is able to distinguish the relative accessibility of the tryptophan residue side chains of lysozyme at positions 62 and 123 from each other and all other tryptophan residues based on their rates of oxidation. Copyright © 2001 John Wiley & Sons, Ltd.
Influence of chain end groups on the matrix‐assisted laser desorption/ionization spectra of polymer blends
Authors: Alicata R. , Montaudo G. , Puglisi C. , Samperi F.
Published: August 2002

The positive ion matrix‐assisted laser desorption/ionization (MALDI) spectrum of an equimolar blend of Nylon 6 (Ny6) and hydroxyl‐terminated polybutyleneterephthalate (PBT) shows a surprisingly strong imbalance between the two components. Since the average molar masses and the polydispersions of the two polymers are comparable, it follows that the efficiency of MALDI is quite different for the two components of the blend. This finding prompted us to a more detailed study, and to synthesize Ny6 and PBT samples terminated with different end groups, in order to analyze their blends by MALDI. The negative ion MALDI spectra of the mixtures investigated show that PBT samples do not yield signals, so that only Ny6 peaks appear in these spectra. By comparing positive and negative ion MALDI spectra of mixtures of Ny6 terminated with various end groups, it was found that the peak intensity depends on the nature of the end groups. The results reported in the present study may help to clarify some fundamental aspects of the mechanisms of ion formation, when MALDI mass spectrometry is applied to macromolecules. End group ionization efficiency appears to be the most important parameter in determining the relative intensity of peaks in the MALDI spectra of the polymer blends investigated. End‐group‐dependent ionization is the key to the rationalization of the relative peak intensities in MALDI spectra of polymer mixtures. Copyright © 2002 John Wiley & Sons, Ltd.
Oxygen isotope corrections for online δ34S analysis
Authors: Fry Brian , Silva Steven R. , Kendall Carol , Anderson Richard K.
Published: August 2002

Elemental analyzers have been successfully coupled to stable‐isotope‐ratio mass spectrometers for online measurements of the δ34S isotopic composition of plants, animals and soils. We found that the online technology for automated δ34S isotopic determinations did not yield reproducible oxygen isotopic compositions in the SO2 produced, and as a result calculated δ34S values were often 1–3‰ too high versus their correct values, particularly for plant and animal samples with high C/S ratio. Here we provide empirical and analytical methods for correcting the S isotope values for oxygen isotope variations, and further detail a new SO2‐SiO2 buffering method that minimizes detrimental oxygen isotope variations in SO2. Published in 2002 by John Wiley & Sons, Ltd.
Hype or Hope: The Potential of Phytoremediation as an Emerging Green Technology
Authors: Schwitzguébel Jean‐Paul
Published: August 2002

Phytoremediation is defined as the use of green plants and their associated microorganisms, soil amendments,
and agronomic techniques to remove, contain, or render harmless environmental pollutants. At the present time,
phytoremediation is an emerging technology and there is still a significant need to pursue both fundamental and
applied research to fully exploit the metabolic and growth habits of higher plants. It is precisely the purpose
of the European COST Action 837 to stimulate the development and evaluate the potential of plant biotechnology
for the removal of organic pollutants and toxic metals from wastewater and contaminated sites. However, green
plants grow under nonsterile conditions and thus strongly interact with many microorganisms, like bacteria and
mycorrhizal fungi. In this context, an Inter‐COST Workshop on bioremediation was recently organized to
address the significance of soil microorganisms for plants, and the importance of their interactions, with
regard to their potential for phytoremediation. Based on the outcomes of this workshop, the potential use of
phytoremediation is presented in this article. © 2001 John Wiley & Sons, Inc.
Contrasting temperatures, waterflows, and light: seasonal habitat selection by young Atlantic salmon and brown trout in a boreonemoral river
Authors: Heggenes Jan , Gunnar Dokk John
Published: August 2002

Habitat use and habitat selection by young Atlantic salmon and brown trout were investigated by direct underwater observation. We sampled during winter and summer water temperatures (low: 3–7°C; high: 9–12°C) coinciding with low and high waterflows (12–20 and 60–80 m3s−1), and during day and night in winter, and on six selected stations in the river. Observations of 396 salmon and 120 trout indicated a distinct seasonal pattern in behaviours and habitat selection. Feeding was the dominant behaviour at high water temperatures during summer. In winter, there was a diurnal pattern in behaviour; both species sheltered in interstitial spaces in the substrate during daylight, but during night held positions on or close to the substrate in slower flowing stream areas. Coarse substrate providing cover was therefore an important habitat factor during daylight at low water temperatures, while slow‐flowing water was important during night. Although spatial niche overlap was considerable both in summer and winter, salmon and trout segregated with respect to meso‐ and microhabitat selection, and relatively more at low temperatures. Both species changed their use of mesohabitats towards more slow‐flowing glide/flat habitats in winter. Irrespective of season, trout preferred in general more slow‐flowing water than salmon did, but the difference was more pronounced in winter. Salmon used a wider range of water depths and in particular water velocities, than did trout. Both species were less tolerant of high water velocities at low water temperatures. The seasonal and diurnal pattern in habitat selection reported have important implications for habitat research and habitat‐hydraulic modelling. Copyright © 2001 John Wiley & Sons, Ltd.
An O(n2) bound for the relaxation time of a Markov chain on cladograms
Authors: Schweinsberg Jason
Published: August 2002

A cladogram is an unrooted tree with labeled leaves and unlabeled internal branchpoints of degree 3. Aldous has studied a Markov chain on the set of n‐leaf cladograms in which each transition consists of removing a random leaf and its incident edge from the tree and then reattaching the leaf to a random edge of the remaining tree. Using coupling methods, Aldous showed that the relaxation time (i.e., the inverse of the spectral gap) for this chain is O(n3). Here, we use a method based on distinguished paths to prove an O(n2) bound for the relaxation time, establishing a conjecture of Aldous. © 2002 John Wiley & Sons, Inc. Random Struct. Alg., 20, 59–70, 2002
Distributed behavior arbitration network: Autonomous behavior control architecture for humanoids
Authors: Shimizu Masaharu , Furuta Takayuki , Tomiyama Ken
Published: August 2002

A new concept of decentralized behavior control architecture for humanoids, termed the Distributed Behavior Arbitration Network, is proposed in this paper. First, policies for constructing the architecture are discussed and then the proposed architecture is designed according to these policies. In the proposed architecture, each competence of a humanoid is differentiated based on the behavior‐based framework and individual agents represent these differentiated competences. An agent consists of NetIBSI, which describes behavior patterns of the agent using state transition network, and the Conflict Resolution Strategy, which mediates with other agents. Autonomous distributed cooperation among agents becomes possible through these two components. The effect of the cooperation among multiple agents is to achieve various behavior patterns for humanoids. The proposed architecture was implemented in two types of humanoids constructed in our laboratory. It was able to realize fall avoidance behavior that required quick response and goal search behavior that required cooperation between two agents. The obtained results demonstrate that the proposed architecture is capable of generating complicated and intelligent behaviors for humanoids. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(6): 32–43, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.1130
Adhesion, lubrication and wear on the atomic scale
Authors: Adams James B. , Hector Louis G. , Siegel Donald J. , Yu Hualiang , Zhong Jun
Published: August 2002

This paper reviews three important aspects of tribology (adhesion, lubrication and wear) on the atomic scale with a focus on our work on aluminum surfaces. Adhesion is critical to the success of many applications but there is no simple analytical model available to predict adhesion between different materials, so we discuss the use of electronic structure methods to investigate adhesion between Al and various ceramics to determine the factors that control adhesion. Lubricants used to control friction usually include ‘boundary additives’ to bind the lubricant more strongly to the surface, so that higher stresses can be employed and wear can be reduced. Little is known about how boundary additives bond to Al surfaces, so we used electronic structure methods to investigate that phenomenon. Regarding wear, we review the literature on molecular dynamics simulations to investigate nanoindentation and wear. We discuss our molecular dynamics simulations of nanoindentation and asperity–asperity shear and the effect of temperature, loading rate, interaction strength and geometry. Copyright © 2001 John Wiley & Sons, Ltd.
Selection models and pattern‐mixture models to analyse longitudinal quality of life data subject to drop‐out
Authors: Michiels Bart , Molenberghs Geert , Bijnens Luc , Vangeneugden Tony , Thijs Herbert
Published: August 2002

Longitudinally observed quality of life data with large amounts of drop‐out are analysed. First we used the selection modelling framework, frequently used with incomplete studies. An alternative method consists of using pattern‐mixture models. These are also straightforward to implement, but result in a different set of parameters for the measurement and drop‐out mechanisms. Since selection models and pattern‐mixture models are based upon different factorizations of the joint distribution of measurement and drop‐out mechanisms, comparing both models concerning, for example, treatment effect, is a useful form of a sensitivity analysis. Copyright © 2002 John Wiley & Sons, Ltd.
Investigating causes of heterogeneity in systematic reviews
Authors: Glasziou P. P. , Sanders S. L.
Published: August 2002

What causes heterogeneity in systematic reviews of controlled trials? First, it may be an artefact of the summary measures used, of study design features such as duration of follow‐up or the reliability of outcome measures. Second, it may be due to real variation in the treatment effect and hence provides the opportunity to identify factors that may modify the impact of treatment. These factors may include features of the population such as: severity of illness, age and gender; intervention factors such as dose, timing or duration of treatment; and comparator factors such as the control group treatment or the co‐interventions in both groups. The ideal way to study causes of true variation is within rather than between studies. In most situations however, we will have to make do with a study level investigation and hence need to be careful about adjusting for potential confounding by artefactual factors such as study design features. Such investigation of artefactual and true causes of heterogeneity form essential steps in moving from a combined effect estimate to application to particular populations and individuals. Copyright © 2002 John Wiley & Sons, Ltd.
Power and sample size requirements for two‐part models
Authors: Lachenbruch Peter A.
Published: August 2002

Two‐part models assume the data has a probability mass at zero and a continuous response for values greater than 0. We construct tests based on the proportion of zeros and the difference among the positive values of a response giving rise to a two degree of freedom χ2 test. This note gives the non‐centrality parameter and finds the power for the test. The power is compared to the simulation results in a recent paper. We derive sample size calculations. We note that some modifications of this procedure may provide better tests if the non‐zero responses are discrete. Published in 2001 by John Wiley & Sons, Ltd.
Two goodness‐of‐fit tests for logistic regression models with continuous covariates
Authors: Pulkstenis Erik , Robinson Timothy J.
Published: August 2002

Assessing goodness‐of‐fit in logistic regression models can be problematic, in that commonly used deviance or Pearson chi‐square statistics do not have approximate chi‐square distributions, under the null hypothesis of no lack of fit, when continuous covariates are modelled. We present two easy to implement test statistics similar to the deviance and Pearson chi‐square tests that are appropriate when continuous covariates are present. The methodology uses an approach similar to that incorporated by the Hosmer and Lemeshow goodness‐of‐fit test in that observations are classified into distinct groups according to fitted probabilities, allowing sufficient cell sizes for chi‐square testing. The major difference is that the proposed tests perform this grouping within the cross‐classification of all categorical covariates in the model and, in some situations, allow for a more powerful assessment of where model predicted and observed counts may differ. A variety of simulations are performed comparing the proposed tests to the Hosmer–Lemeshow test. Copyright © 2002 John Wiley & Sons, Ltd.
Residual‐based tree‐structured survival analysis
Authors: Keleş Sündüz , Segal Mark R.
Published: August 2002

Extensions of various non‐parametric regression techniques (for example, additive models, trees, MARS) have been devised for right censored survival data. These approaches directly handle the difficulties posed by censoring. However, it is possible to bypass these difficulties by utilizing standard non‐parametric regression procedures applied with (say) martingale residuals as outcome. Analytic correspondences between the direct and residual‐based approaches have been established for additive models while more qualitative comparisons have been provided for MARS. Here we develop such correspondences for tree‐structured regression. In particular, we provide an analytic relationship between logrank and martingale residual sum‐of‐squares split functions that explains the widely observed similarity of the resultant trees. Further investigation is provided by simulation and an illustrative example using time to AIDS with data deriving from a Western Australian HIV cohort study. Copyright © 2002 John Wiley & Sons, Ltd.
Eleutherococcus senticosus reduces cardiovascular stress response in healthy subjects: a randomized, placebo‐controlled trial
Authors: Facchinetti F. , Neri I. , Tarabusi M.
Published: August 2002

The number of studies devoted to the scientific evaluation of phytotherapy is rapidly increasing since Western patients seem more oriented towards so‐called ‘alternative medicine’. Bearing such arguments in mind we decided to address attention to Eleutherococcus senticosus, a root of the Ginseng family known for thousands of years in China as a remedy for psychological distress. Forty‐five paid, healthy volunteers (20 males, 25 females) were recruited. Entry criteria were: good health, age 18–30 years, student and a Symptoms Rating Test score <10. At screening evaluation subjects were randomized to receive orally either placebo (Pl group) or Eleutherococcus senticosus (Es group) for 30 days, in a double‐blind design. Subjects were submitted to a stressful cognitive task, the Stroop Colour–Word test (Stroop CW), both before and after treatment. Stroop CW increased heart rate (HR) and systolic BP in every subject. In females there was a greater response than in males in terms of both systolic and diastolic BP. For both genders, the HR response to Stroop CW was reduced by Es treatment while no changes were found after Pl. In females, systolic BP was also reduced in Es group while it remained unchanged in Pl group. This study demonstrated that treatment with Eleutherococcus senticosus is able to reduce cardiovascular responses to stress in healthy young volunteers, while placebo was ineffective. Eleutherococcus senticosus is confirmed to be helpful for stress adaptation. Copyright © 2002 John Wiley & Sons, Ltd.
Health, performance and emotional intelligence: an exploratory study of retail managers
Authors: Slaski Mark , Cartwright Susan
Published: August 2002

Contemporary theories place emotions and self‐regulation at the centre of a dynamic process of stress. Emotional Intelligence (EQ) is the ability to perceive, understand and reflectively manage one's own emotions and those of others. This study, which was situated within the management population (n = 224) of a large retail organization, investigates the relationship between a measure of EQ, subjective stress, distress, general health, morale, quality of working life and management performance. Significant correlations in the expected direction were found, indicating that managers who scored higher in EQ suffered less subjective stress, experienced better health and well‐being, and demonstrated better management performance. Copyright © 2002 John Wiley & Sons, Ltd.
The quest for competence in systemic research and practice
Authors: Ulrich Werner
Published: August 2002

How can we develop competence in research and professional practice? This essay tries to answer the question from the perspective of critical systems thinking, that is, through an approach that aims to promote reflective research and practice. The paper originated in discussions on the nature of research, with research students and professionals from different fields—among these the domains of business and public management, operational research and management science, social planning and evaluation research, public health, poverty research, social work and social policy, environmental research, city and regional planning, adult education and civic studies. With its publication the author hopes to encourage a wide readership of research students, researchers and professionals in these and other fields of practice who wish to clarify their personal notion of competence. The essay addresses them in a direct and personal way. Copyright © 2001 John Wiley & Sons, Ltd.
Antiapoptotic and cytotoxic properties of delta opioid peptide [D‐Ala2,D‐Leu5]enkephalin in PC12 cells
Authors: Hayashi Teruo , Tsao Li‐I , Su Tsung‐Ping
Published: August 2002

The delta opioid peptide [D‐Ala2,D‐Leu5]enkephalin (DADLE) has been shown to promote organ survival and to protect against methamphetamine‐induced neurodegeneration. However, the cellular mechanisms of these actions of DADLE are not totally clear. We examined the action of DADLE in serum‐deprived pheochromocytoma cells (PC12) and found that DADLE protected against cell death in those cells. However, the dose–response curves of the protective effects of DADLE are U‐shaped as judged by three biochemical or morphological assays: the LDH release, the DNA laddering, and the apoptotic nuclei. It was found that femtomolar to picomolar concentrations of DADLE are antiapoptotic, whereas micormolar concentrations of DADLE are cytotoxic in PC12 cells. The protective effect of DADLE could be attenuated by a selective delta2 opioid antagonist and the cytotoxic action of DADLE was reduced by a selective mu opioid receptor antagonist. The treatment of cells with PD98059, a selective inhibitor of ERK kinase (MEK), or the transfection of cells with a dominant interfering form of MEK (MEK‐KA97) blocked both the protective effect of DADLE and the ERK phosphorylation induced by DADLE. Cytotoxic concentrations of DADLE, on the other hand, caused an increase of Fas‐ligand (FasL) in PC12 cells that was attenuated by a selective mu antagonist. Our results suggest, therefore, that endogenous opioid peptides may, at low concentrations, promote cell survival via the MEK‐ERK pathway perhaps through delta2 opioid receptors, whereas they may kill cells at high concentrations via the activation of FasL through an as‐yet unknown mechanism involving mu opioid receptors. Synapse 43:86–94, 2002. © 2001 Wiley‐Liss, Inc.
Evidence for activation of histamine H3 autoreceptors during handling stress in the prefrontal cortex of the rat
Authors: Westerink Ben H.C. , Cremers Thomas I.F.H. , De Vries Jan B. , Liefers Hans , Tran Nan , De Boer Peter
Published: August 2002

On‐line microdialysis of histamine in 10‐min samples of the prefrontal cortex of the conscious rat is described. The HPLC‐fluorescent assay for histamine in dialysates has been significantly simplified by using only one postcolumn reagent line instead of the three reagent lines described in earlier methods. The method is selective, sensitive (detection limit: 2–3 fmol on column), and linear over a large concentration range. Basal values of histamine decreased to about 50% of basal levels during infusion of tetrodotoxin (5 × 10‐6 M). Handling rats for 15 min increased histamine in dialysates to about 300% of basal levels. When tetrodotoxin (10‐6 M) was applied during handling the increase in histamine release was strongly (about 80%) suppressed. The handling‐induced increase in histamine was used as a paradigm to investigate the functional activity of histamine H3 autoreceptors during mild stress or arousal. An H3 receptor specific agonist (α‐methylhistamine; 10‐5 M) and antagonist (thioperamide; 10‐5 M) were infused into the frontal cortex via the microdialysis probe. The effect of handling on histamine release was potentiated during infusion of thioperamide and fully suppressed during infusion of α‐methylhistamine. These results clearly illustrate the efficacy of the H3 autoreceptor in modulating stimulated histamine release during natural stimulatory conditions. Synapse 43:238–243, 2002. © 2002 Wiley‐Liss, Inc.
In vivo binding properties of [carbonyl‐11C]WAY‐100635: Effect of endogenous serotonin
Authors: Maeda Jun , Suhara Tetsuya , Ogawa Masanao , Okauchi Takashi , Kawabe Kouichi , Zhang Ming‐Rong , Semba Jun'Ichi , Suzuki Kazutoshi
Published: August 2002

[Carbonyl‐11C]WAY‐100635 has been reported to be a useful ligand for the investigation of 5‐HT1A receptor imaging in vivo. However, the cellular distribution and the influence of endogenous serotonin (5‐HT) on in vivo binding have not been fully examined. In this study, we investigated the effect of 5,7‐dihydroxytryptamine‐produced destruction of 5‐HT neurons, reserpine‐induced 5‐HT depletion, and fenfluramine‐induced 5‐HT increase on [carbonyl‐11C]WAY‐100635 binding in vivo. There was no significant change in the uptake of [carbonyl‐11C]WAY‐100635 in the slice of 5‐HT denervated rat brain except in the raphe nucleus, where 5‐HT cell bodies exist. There was no obvious effect of enhanced 5‐HT release by fenfluramine or decreased release by reserpine on [carbonyl‐11C]WAY‐100635 binding in the dissected brain region. No significant effect was observed in the time course of [carbonyl‐11C]WAY‐100635 in the hippocampus and frontal cortex measured by PET. These results indicated that the in vivo binding of [carbonyl‐11C]WAY‐100635 in the hippocampus and cerebral cortex mainly reflects postsynaptic 5‐HT1A receptor binding, and that this binding is not sensitive to endogenous 5‐HT. Synapse 40:122–129, 2001. © 2001 Wiley‐Liss, Inc.
Differential behavioral responses to cocaine are associated with dynamics of mesolimbic dopamine proteins in Lewis and Fischer 344 rats
Authors: Haile Colin N. , Hiroi Noboru , Nestler Eric J. , Kosten Therese A.
Published: August 2002

Differential behavioral and biochemical responses to drugs of abuse may reflect genetic makeup as suggested by studies of inbred Lewis (LEW) and Fischer 344 (F344) rats. We investigated locomotor activity, stereotypy signs, and levels of specific proteins in the nucleus accumbens (NAc) and ventral tegmental area (VTA) in these strains at baseline and following chronic administration of cocaine (30 mg/kg/day for 14 days). Using Western blot analysis, we replicated our previous findings of baseline strain differences and found lower levels of ΔFosB immunoreactivity in NAc of F344 vs. LEW rats. F344 rats showed greater baseline locomotor activity, sniffing, and grooming compared to LEW rats. Chronic cocaine increased ΔFosB levels in NAc in both strains, whereas adaptations in other proteins were induced in F344 rats only. These included reduced levels of tyrosine hydroxylase (TH) in NAc and increased TH and glial fibrillary acidic protein (GFAP) immunoreactivity in VTA. Chronic cocaine led to greater increases in overall stereotypy in F344 vs. LEW rats and decreased exploratory behaviors in LEW rats. Opposing effects by strain were seen in locomotor activity. Whereas F344 rats showed higher initial activity levels that decreased with cocaine exposure (tolerance), LEW rats showed increased activity over days (sensitization) with no strain differences seen at 14 days. Further, conditioned locomotor activation to vehicle injections was greater in F344 vs. LEW rats. These results suggest that behavioral responsiveness to chronic cocaine exposure may reflect dynamics of mesolimbic dopamine protein levels and demonstrate the role of genetic background in responsiveness to cocaine. Synapse 41:179–190, 2001. © 2001 Wiley‐Liss, Inc.
Morphine acutely and persistently attenuates nonvesicular GABA release in rat nucleus accumbens
Authors: Schoffelmeer Anton N.M. , Wardeh George , Vanderschuren Louk J.M.J.
Published: August 2002

Withdrawal from repeated exposure to morphine causes a long‐lasting increase in the reactivity of nucleus accumbens nerve terminals towards excitation. The resulting increase in action potential‐induced exocytotic release of neurotransmitters, associated with behavioral sensitization, is thought to contribute to its addictive properties. We recently showed that activation of N‐methyl‐D‐aspartate (NMDA) as well as dopamine (DA) D1 receptors in rat striatum causes tetrodotoxin‐insensitive transporter‐dependent GABA release. Since sustained changes in extracellular GABA levels may play a role in drug‐induced neuronal hyperresponsiveness, we examined the acute and long‐lasting effect of morphine on this nonvesicular GABA release in rat nucleus accumbens slices. The present study shows that morphine, through activation of μ‐opioid receptors, reduces nonvesicular NMDA‐induced [3H]GABA release in superfused nucleus accumbens slices. Moreover, prior repeated morphine treatment of rats (10 mg/kg, sc, 14 days) caused a reduction in NMDA‐stimulated [3H]GABA release in vitro until at least 3 weeks after morphine withdrawal. This persistent neuroadaptive effect was not observed studying dopamine D1 receptor‐mediated [3H]GABA release in nucleus accumbens slices. Moreover, this phenomenon appeared to be absent in slices of the caudate putamen. Interestingly, even a single exposure of rats to morphine (>2 mg/kg) caused a long‐lasting inhibition of NMDA‐induced release of GABA in nucleus accumbens slices. These data suggest that a reduction in nonvesicular GABA release within the nucleus accumbens, by enhancing the excitability of input and output neurons of this brain region, may contribute to the acute and persistently enhanced exocytotic release of neurotransmitters from nucleus accumbens neurons in morphine‐exposed rats. Synapse 42:87–94, 2001. © 2001 Wiley‐Liss, Inc.
Theoretical framework for the continuous early validation (CEaVa) method
Authors: Larsen Robert F. , Buede Dennis M.
Published: August 2002

Systems being developed today make extensive and complex use of advanced technology. Many, if not most, of these systems are being produced but are not used or useful on delivery because the wrong problem was solved. A major cause for this shortfall in system development is due to changes in the operational environment of the intended system while the development process is ongoing. Significant sections of the literature discuss the need to get stakeholders involved earlier in the development process to correct this problem. However, no one has developed a detailed framework that accomplishes this intent. This paper defines a method involving a four‐step sequence that validates the entire system design process early and continuously to ensure that the right problem is being solved. The method is called Continuous Early Validation (CEaVa). It is a method that increases the likelihood of producing the correct system. The method develops visibility of potential disconnects among stakeholders' needs, original written requirements, organizational policy, and derived requirements. The CEaVa method validates the external and internal consistency of the problem statement. Additionally, CEaVa facilitates consensus on trade offs and priorities, resolving the potential disconnects with decision analytical reasoning for trade‐off analysis. The CEaVa method improves the development process and ultimately the system itself by increasing the likelihood of building the right system within budget and schedule. © 2002 Wiley Periodicals, Inc. Syst Eng 5: 223–241, 2002
5‐Aza‐2′‐deoxycytidine‐induced cytotoxicity and limb reduction defects in the mouse
Authors: Rosen Mitchell B. , Chernoff Neil
Published: August 2002

Background

5‐Aza‐2′‐deoxycytidine (dAZA), causes hindlimb phocomelia in CD‐1 mice. Studies in our laboratory have examined the hypothesis that compound‐ induced changes in gene expression may uniquely affect hindlimb pattern formation. The present study tests the hypothesis that dAZA causes limb dysplasia by inducing cytotoxicity among rapidly proliferating cells in the limb bud mesenchyme.

Methods

Pregnant CD‐1 mice were given a teratogenic dose of dAZA (i.p.) at different times on GD 10 and fetuses evaluated for skeletal development in both sets of limbs by standard methods. Using general histology and BrdU immunohistochemistry, limb mesenchymal cell death and cell proliferation were then assessed in embryos at various times post dosing, shortly after initial limb bud outgrowth. The effect of dAZA on early limb chondrogenesis was also studied using Northern analysis of scleraxis and Alcian blue staining of whole mount limb buds.

Results

Compound related hindlimb defects were not restricted to a specific set of skeletal elements but consisted of a range of temporally related limb anomalies. Modest defects of the radius were observed as well. These results are consistent with a general insult to the limb mesenchyme. Mesenchymal cell death and reduced cell proliferation were also observed in both sets of limbs. The timing and location of these effects indicate a role for cytotoxicity in the etiology of dAZA induced limb defects. These effects also agree with the greater teratogenicity of dAZA in the hindlimb because they were more pronounced in that limb. The expression of scleraxis, a marker of early chondrogenesis, was reduced 12 hr after dAZA exposure, a time coincident with maximal cell death, as was the subsequent emergence of Alcian blue stained long bone anlagen.

Conclusions

These findings support the hypothesis that cytotoxic changes in the limb bud mesenchyme during early limb outgrowth can induce the proximal limb truncations characteristic of phocomelia after dAZA administration. Teratology 65:180–190, 2002. © 2002 Wiley‐Liss, Inc.
Epidemiology of Down syndrome (Trisomy 21), Hawaii, 1986–97
Authors: Forrester Mathias B. , Merz Ruth D.
Published: August 2002

Background

The live birth prevalence of Down syndrome is approximately 10 per 10,000 live births in the United States. Down syndrome prevalence has been reported to change over time and to vary by selected demographic factors.

Methods

Data from a population‐based birth defects registry in Hawaii involving 363 Down syndrome cases delivered during 1986–97 were used to calculate overall prevalence and to investigate secular trends and differences by selected demographic factors.

Results

The total (live birth, fetal death, and elective termination) prevalence was 14.74 per 10,000 live births and fetal deaths. The unadjusted live birth prevalence was 8.67 per 10,000 live births. The adjusted live birth (live births and proportion of elective terminations expected to have resulted in live births) prevalence was 12.59 per 10,000 live births. No significant secular trends were observed for either total prevalence (P = 0.688) or adjusted live birth prevalence (P = 0.604). The total Down syndrome prevalence per 10,000 live births was highest for Far East Asians (22.01), followed by whites (17.06), Filipinos (15.94), and Pacific Islanders (9.21). Prevalence per 10,000 births was higher in metropolitan Honolulu (18.57) than in the rest of Hawaii (14.15). After adjusting for maternal age, however, the differences within the demographic groups were not statistically significant.

Conclusions

The live birth prevalence of Down syndrome in Hawaii during 1986–97 was lower than reported in the literature. Prevalence did not change significantly over time. Any differences in prevalence by maternal race/ethnicity and place of residence appeared to result from differences in maternal age distribution. Teratology 65:207–212, 2002. © 2002 Wiley‐Liss, Inc.
Continued occurrence of Accutane®‐exposed pregnancies
Authors: Honein M.A. , Paulozzi L.J. , Erickson J.D.
Published: August 2002

Background

Accutane® a teratogenic prescription drug licensed to treat severe, recalcitrant nodular acne. First‐trimester pregnancy exposure can cause major birth defects. The manufacturer began a Pregnancy Prevention Program (PPP) in 1988; however, exposed pregnancies continue to occur. In 1996, the manufacturer began a direct‐to‐consumer advertising campaign, raising concerns of more exposed pregnancies.

Methods

We examined trends in Accutane use by reproductive‐aged women. We also interviewed a series of 14 women in California who had recent Accutane‐exposed pregnancies to identify opportunities for prevention.

Results

The estimated number of Accutane prescriptions for reproductive‐aged women has more than doubled in the past 10 years; it is the most widely used teratogenic drug in the United States, with approximately 2.5 per 1,000 reproductive‐aged women exposed to Accutane in 1999. One‐half of the women interviewed reported seeing an advertisement for prescription acne treatment before taking Accutane. Eight of the 14 women used no contraception at the time of the exposed pregnancy; 13 of the 14 women did not use two forms of contraception. Four of the 14 women did not have pregnancy tests before starting Accutane. None reported seeing all PPP components, and four saw only the information on the pill packet. These 14 pregnancies resulted in four live infants who had no apparent birth defects, one live‐born infant with multiple defects, four spontaneous abortions, and five induced abortions.

Conclusions

The increase in Accutane use observed among females may be exacerbated by advertising. Physicians and patients must use more caution with teratogenic prescription drugs. Teratology 64:142–147, 2001. Published 2001 Wiley‐Liss, Inc.
The soul of scholarship
Authors: Mallard Kina S.
Published: August 2002

Higher education in the twenty‐first century calls for a paradigm shift in scholarship—a new approach that encourages academicians to consider not only the current practice and product of research at their institutions but also the well‐being of the practitioner—in short, to explore the soul of scholarship.
Occurrence of 20S RNA and 23S RNA replicons in industrial yeast strains and their variation under nutritional stress conditions
Authors: López Victoria , Gil Rosario , Vicente Carbonell José , Navarro Alfonso
Published: August 2002

We have characterized industrial yeast strains used in the brewing, baking, and winemaking industries for the presence or absence of cytoplasmic single‐stranded 20S and 23S RNAs. Furthermore, the variation of intracellular concentrations of these replicons in brewing and laboratory strains under nutritional stress conditions was determined. Our results show a correlation between the relative abundance of these replicons and exposure of yeast to nutritionally stressful conditions, indicating that these RNAs could be employed as molecular probes to evaluate the exposure of 20S+ and/or 23S+ yeast strains to stress situations during industrial manipulation. During this study, several 20S−23S+ Saccharomyces cerevisiae strains were isolated and identified. This is the first time that a yeast strain containing only 23S RNA has been reported, demonstrating that 20S RNA is not required for 23S RNA replication. Copyright © 2002 John Wiley & Sons, Ltd.
A versatile enzyme immunoassay for the determination of progestogens in feces and serum
Authors: Graham Laura , Schwarzenberger Franz , Möstl Erich , Galama Wieke , Savage Anne
Published: August 2002

The ability of zoos to monitor the reproductive status of their animals can vastly improve the effectiveness of husbandry/management practices, and noninvasive methods such as fecal steroid analysis are the easiest to apply in a zoo setting. Furthermore, enzyme immunoassay (EIA) is preferred to radioimmunoassay (RIA) as the method of quantifying hormones because EIAs do not involve the use, storage, and disposal of radioactive materials. However, progesterone is excreted in the feces as predominantly unconjugated metabolites (progestogens) and, until recently, antibodies able to cross‐react with a variety of progestogens were used primarily in RIAs. An EIA using a broad‐spectrum progestogen antibody is described and applied to serum and/or fecal samples from female African elephants, black rhinoceros, white rhinoceros, okapi, and hippopotami. The clear progestogen profiles generated in these species suggest that the described EIA would be as versatile as the RIA using the same antibody and could be a practical and economical alternative to RIAs for monitoring gonadal function via progestogen analysis in zoo species. Zoo Biol 20:227–236, 2001. © 2001 Wiley‐Liss, Inc.
Intraoperative Transfusion: Is It a Real Prognostic Factor of Periampullary Cancer Following Pancreatoduodenectomy?
Authors: Park Sang‐Jae , Kim Sun‐Whe , Jang Jin‐Young , Lee Kuhn‐Uk , Park Yong‐Hyun
Published: August 2002

The purpose of this study was to clarify the prognostic significance of transfusion following pancreatoduodenectomy for periampullary cancers. We analyzed 357
periampullary cancers from 1985 to 1997 (ampullary cancer 130 cases,
distal bile duct cancer 141 cases, pancreatic head cancer 86 cases). A total of 215 (60%) of the 357 patients have received intraoperative transfusion. The 5‐year survival rate of 130 ampullary cancer patients was 59%; altogether, 76 patients (58%) underwent intraoperative transfusion. The 5‐year survival rate of patients without intraoperative transfusion was 79%, whereas that of patients with a transfusion was 47% (p = 0.029). Following multivariate analysis, intraoperative transfusion was found to be an independent poor prognostic factor for those with ampullary cancer
(relative risk 2.174). Among those with common bile duct cancer, the overall 5‐year survival rate was 33%, and the 5‐year survival rates for patients with (n = 87) or without
(n = 54) transfusion were 25% and 38%, respectively,
which did not reach statistical significance (p =
0.0717). For those with pancreatic head cancer, the overall 5‐year survival rate was 16%, and there was no survival difference between transfused (n = 52) and untransfused
(n = 34) patients. In the present study the reason was not clear, although intraoperative transfusion was an independent significant prognostic factor for ampullary cancer. Careful dissection to minimize intraoperative bleeding is mandatory during pancreatoduodenectomy for ampullary cancer.
Future of Thyroid Surgery and Training Surgeons to Meet the Expectations of 2000 and Beyond
Authors: Harness Jay K. , van Heerden Jon A. , Lennquist Sten , Rothmund Matthias , Barraclough Bruce H. , Goode A.W. , Rosen Irving B. , Fujimoto Yoshihide , Proye Charles
Published: August 2002

What is the future of thyroid surgery in the new millennium? How can surgeons keep abreast of advances in thyroid endocrinology, genetics, surgical therapy, and other aspects of thyroid disease management? How should surgeons be trained to become highly competent in thyroid disease and to perform safe, effective thyroid operative procedures? Nine internationally recognized endocrine surgeons were asked to express their views on these and related subjects. They noted that advances in molecular biology, pathology, and genetics of thyroid disease should allow more tailored surgical approaches during the twenty‐first century. Current training of general surgical residents in thyroid and other types of endocrine surgery is highly variable, which may contribute to increased complication rates and number of second operations. The leadership for addressing these deficiencies and promoting a more organized approach to thyroid disease management should come from national endocrine surgery associations and their leaders. It is incumbent upon endocrine surgeons to maintain their central role in the management of many aspects of thyroid disease. Organizing teams of specialists into thyroid centers (centers of excellence) can (1) increase efficiency; (2) increase quality of care; (3) decrease costs; (4) encourage a more individualized approach to surgery; (5) lower complication rates; and (6) foster innovation in technology and disease management. Two years of additional fellowship training in thyroid and endocrine surgery is now being advocated by increasing numbers of national endocrine surgical associations as the best way to prepare surgeons for society's needs for highly skilled, competent thyroid surgeons of the future.
Curative Resection of Microgastrinomas Based on the Intraoperative Secretin Test
Authors: Kato Masayuki , Imamura Masayuki , Hosotani Ryo , Shimada Yutaka , Doi Ryuichiro , Itami Atsushi , Komoto Izumi , Kosaka Tadako , Konishi Junji
Published: August 2002

The intravenous secretin injection test (secretin test) has been used for the differential diagnosis of gastrinoma. In this study we report that the intraoperative secretin test (IOS test) is also useful for determining the extent of curability in patients with Zollinger‐Ellison syndrome (ZES). Twelve patients with ZES underwent surgical exploration and the IOS test. The results of the IOS test were obtained by rapid radioimmunoassay of the serum gastrin level (IRG) within 60 minutes. The test was diagnosed as negative when the maximum increase of serum IRG was less than 80 pg/ml and also less than 20% of the basal serum IRG level. Three of the twelve patients underwent pancreatoduodenectomy (PD), and two patients underwent distal pancreatectomy. Extirpation of duodenal tumors with dissection of regional lymph nodes was performed in seven patients. In two of the seven patients the IOS test remained positive after extirpation of the duodenal tumors and the dissection of regional lymph nodes. In one patient PD was performed on the basis of the positive results, and the IOS test became negative after PD. In the other patient, two tiny metastatic liver tumors were identified and were resected, but the IOS test did not become negative. We closed the abdomen in 11 patients when we obtained negative results from the IOS test. The results of the IOS test were almost identical to the data obtained by the standard assay postoperatively. The serum IRG levels of all but one patient fell to the normal level, and the secretin test became negative postoperatively. The IOS test is thus useful and indispensable for curative resection of microgastrinomas in patients with ZES.