bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient expression, purification and characterization of mouse salivary α‐amylase secreted from methylotrophic yeast, Pichia pastoris
Authors: Kato Shinya , Ishibashi Matsujiro , Tatsuda Daisuke , Tokunaga Hiroko , Tokunaga Masao
Published: September 2002

We constructed a secretion vector of mouse salivary α‐amylase, pPAM, using the AOX1 promoter‐terminator and the secretion signal of 128 kDa pGKL killer protein, for an alternative yeast, Pichia pastoris. Taking advantage of multicopy insertion of the expression cassette and optimized growth conditions, we succeeded in highly efficient extracellular production (∼240 µg/ml) of mouse α‐amylase in the 10 ml scale by conventional flask culture: this efficiency was about 90‐fold higher than that of Saccharomyces cerevisiae. Growth temperature of cells was critical for efficient production of α‐amylase. P. pastoris transformants secreted both core‐glycosylated and non‐glycosylated α‐amylase molecules with a glycosylated:non‐glycosylated ratio of about 20:80. Both glycosylated and non‐glycosylated α‐amylases were purified separately to apparent homogeneity. The signal sequence was correctly processed in both species, and the molecular masses of glycosylated and non‐glycosylated α‐amylase were determined to be 58 600 and 56 300, respectively, by mass spectrometry. We further studied the outer chain glycosylation of engineered mouse α‐amylase secreted by P. pastoris. Copyright © 2001 John Wiley & Sons, Ltd.
Alterations of the glucose metabolism in a triose phosphate isomerase‐negative Saccharomyces cerevisiae mutant
Authors: Compagno Concetta , Brambilla Luca , Capitanio Daniele , Boschi Francesco , Maria Ranzi Bianca , Porro Danilo
Published: September 2002

The absence of triose phosphate isomerase activity causes an accumulation of only one of the two trioses, dihydroxyacetone phosphate, and this produces a shift in the final product of glucose catabolism from ethanol to glycerol (Compagno et al., 1996). Alterations of glucose metabolism imposed by the deletion of the TPI1 gene in Saccharomyces cerevisiae were studied in batch and continuous cultures. The Δtpi1 null mutant was unable to grow on glucose as the sole carbon source. The addition of ethanol or acetate in media containing glucose, but also raffinose or galactose, relieved this effect in batch cultivation, suggesting that the Crabtree effect is not the primary cause for the mutant's impaired growth on glucose. The addition of an energy source like formic acid restored glucose utilization, suggesting that a NADH/energy shortage in the Δtpi1 mutant could be a cause of the impaired growth on glucose. The amount of glycerol production in the Δtpi1 mutant could represent a good indicator of the fraction of carbon source channelled through glycolysis. Data obtained in continuous cultures on mixed substrates indicated that different contributions of glycolysis and gluconeogenesis, as well as of the HMP pathway, to glucose utilization by the Δtpi1 mutant may occur in relation to the fraction of ethanol present in the media. Copyright © 2001 John Wiley & Sons, Ltd.
The morbidity, time course and predictive factors for persistent post‐thoracotomy pain
Authors: Gotoda Yumiko , Kambara Noriko , Sakai Toshiko , Kishi Yoshihiko , Kodama Ken , Koyama Tetsuo
Published: September 2002

After thoracotomy, patients often suffer from a persistent pain syndrome called post‐thoracotomy pain. To elucidate morbidity, time course, and predictive factors for this syndrome, we analyzed follow‐up data for 85 post‐thoracotomy patients. We used a four‐point scale to assess pain: none, slight, moderate and severe. Of 85 patients, 50 reported pain (39 slight, 11 moderate) one day after surgery. A year after surgery, the patients were polled using a simple questionnaire received by the mail. Sixty patients reported persistent pain (34 slight, 14 moderate, 12 severe) a month after surgery, and 35 patients reported persistent pain (33 slight, two moderate) around the time of the poll (1 year after surgery). Although pain deterioration was observed in 40% (34/85) of patients during month 1 after surgery, pain alleviation was seen in 48% (41/85) of patients during months 2–12. Stepwise regression analysis revealed that female gender and pain at postoperative day 1 were predictive for persistent pain both 1 month and 1 year after thoracotomy. Among 35 patients with persistent pain 1 year after surgery, 24 cases reported paresthesia–dysesthesia, and 14 cases reported hypoesthesia. The present data thus suggests that persistent pain is common and often severe 1 month after surgery but is alleviated after 1 year. Clinical time course and symptoms indicate that nerve impairment rather than simple nociceptive impact may be involved in this syndrome.
ENSO as a forewarning tool of regional fire occurrence in northern Patagonia, Argentina
Authors: Kitzberger Thomas
Published: August 2002

Composite series of ENSO indices recorded over 36 months preceding major fire
years in four National Parks in northern Patagonia were compared with series
of these indices for individual years over the period 1950–1996 by means
of an additive temporal phase coherence index. Logistic regressions of the
dichotomous variable high vs low regional fire occurrence against the
coherence index gained highest significant classificatory power using an index
based on SST anomaly data between January of year –3 to August of year
–1. Thus, warnings of extreme fire seasons could be declared as early as
3 months before the full fire season starts (i.e. early September). A regional
fire season readiness index is proposed based on the periodicity of the
Southern Oscillation, strong links with climate at particular regions of the
globe, and empirically derived climatic controls on fine fuel buildup and
coarse fuel desiccation. This long-range alerting tool could help
decision-makers prepare preventative measures to mitigate the effects of
large, high intensity wildfire seasons. However, it should be used with
caution given that differences in timing in the onset of ENSO events and
instability in teleconnection patterns could change climatic sequences,
differentially affecting fire susceptibility.
Alcohol Seeking by Rats: Action or Habit?
Authors: Dickinson Anthony , Wood Nigel , Smith Janice W.
Published: September 2002

In two experiments, we examined the relative susceptibility to outcome devaluation of lever pressing by rats for either a 10% ethanol solution or food pellets. The rats were trained to press different levers for these two reinforcers using a sucrose-substitution procedure. An aversion was then conditioned from either the ethanol solution or the food pellets by pairing consumption with illness induced by lithium chloride. When instrumental performance was subsequently tested in extinction, the rats pressed less on the pellet lever if the pellets, rather than the ethanol, had been devalued by aversion conditioning. By contrast, performance on the ethanol lever was unaffected by whether the ethanol or pellets were devalued. Moreover, noncontingent presentations of the devalued reinforcer had no impact on test performance. The differential resistance to outcome devaluation suggests that, in contrast to food seeking, alcohol seeking is a stimulus-response habit rather than a goal-directed action mediated by a representation of the action-outcome contingency.
Non-destructive microstructural analysis with depth resolution: application to seashells
Authors: Zolotoyabko E. , Quintana J. P.
Published: September 2002

Energy-variable X-ray diffraction at a synchrotron beamline has been used to control the X-ray penetration depth and thus to study structural parameters in polycrystalline and textured materials with depth resolution. This approach was applied to the investigation of the depth evolution of microstructure in the nacre layer of bivalvia seashells. According to conventional X-ray diffraction and scanning electron microscopy, the nacre layer in the seashells ofAcanthocardia tuberculataunder investigation consists of large [001]-oriented lamellae packed nearly parallel to the inner shell surface. In this paper, attention is focused on the microstructural information that can be extracted from the shapes of diffraction profiles (line profile analysis) measured at X-ray energies that are varied by small steps. Depth dependences of the thickness of the lamellae and the average microstrain fluctuation are revealed.
Consumer response to the preferred brand out‐of‐stock situation
Authors: Verbeke Willem , Farris Paul , Thurik Roy
Published: September 2002

The goal of this study was to gauge brand loyalty. To do this, a brand loyalty acid test was used, which involved an out‐of‐stock (OOS) experiment where the complete product line of a brand was removed from several stores in order to estimate the OOS responses of consumers. Three types of OOS responses were identified: switching brands; switching stores to get one’s favorite brand; and postponing purchase of a specific brand. The present study revealed that the brand loyalty of the consumers participating in the OOS experiment was substantial, as a large percentage of them switched stores or postponed purchase. The study also showed that neither competitive conditions of the retailer nor assortment change had any effect on consumers’ OOS responses. The most potent variables that affected OOS responses were the way consumers organized their shopping trips: store loyals more than others switched stores by OOS; and consumers with a small purchase amount per shopping trip were less likely to switch stores and more likely to postpone purchase. There also was a slight tendency for the consumer to spend less in the store during the OOS period. This paper suggests the implications of these findings for retailers and manufacturers.
The impact of principal leadership behaviors on instructional practice and student engagement
Authors: Quinn David M.
Published: September 2002

For decades educators have espoused the importance of the principal as the instructional leader of the school. The purpose of this study was to identify the relationship between principal leadership behaviors and teacher instructional practice descriptors. This relationship was observed among schools participating in a systemic school improvement process. The study included eight elementary, eight middle, and eight high schools in the USA. Teachers in each school were surveyed on the principal’s instructional leadership abilities. Student and teacher engagement data were collected through school‐wide observations using the instructional practices inventory. Instructional leadership dimensions were found to correlate highly with instructional practice descriptors. This study confirms the significance of instructional leadership and provides specific insight into the nature of that leadership.
ON A GENERALIZED LORENZ CANONICAL FORM OF CHAOTIC SYSTEMS
Authors: ČELIKOVSKÝ SERGEJ , CHEN GUANRONG
Published: September 2002

This paper shows that a large class of systems, introduced in [Čelikovský & Vaněček, 1994; Vaněček & Čelikovský, 1996] as the so-called generalized Lorenz system, are state-equivalent to a special canonical form that covers a broader class of chaotic systems. This canonical form, called generalized Lorenz canonical form hereafter, generalizes the one introduced and analyzed in [Čelikovský & Vaněček, 1994; Vaněček & Čelikovský, 1996], and also covers the so-called Chen system, recently introduced in [Chen & Ueta, 1999; Ueta & Chen, 2000].

Thus, this new generalized Lorenz canonical form contains as special cases the original Lorenz system, the generalized Lorenz system, and the Chen system, so that a comparison of the structures between two essential types of chaotic systems becomes possible. The most important property of the new canonical form is the parametrization that has precisely a single scalar parameter useful for chaos tuning, which has promising potential in future engineering chaos design. Some other closely related topics are also studied and discussed in the paper.
CYCLING CHAOS IN ONE-DIMENSIONAL COUPLED ITERATED MAPS
Authors: PALACIOS ANTONIO
Published: September 2002

Cycling behavior involving steady-states and periodic solutions is known to be a generic feature of continuous dynamical systems with symmetry. Using Chua's circuit equations and Lorenz equations, Dellnitz et al. [1995] showed that "cycling chaos", in which solution trajectories cycle around symmetrically related chaotic sets, can also be found generically in coupled cell systems of differential equations with symmetry. In this work, we use numerical simulations to demonstrate that cycling chaos also occurs in discrete dynamical systems modeled by one-dimensional maps. Using the cubic map f (x, λ) = λx - x3 and the standard logistic map, we show that coupled iterated maps can exhibit cycles connecting fixed points with fixed points and periodic orbits with periodic orbits, where the period can be arbitrarily high. As in the case of coupled cell systems of differential equations, we show that cycling behavior can also be a feature of the global dynamics of coupled iterated maps, which exists independently of the internal dynamics of each map.
CELLULAR NEURAL NETWORKS: SPACE-DEPENDENT TEMPLATE, MOSAIC PATTERNS AND SPATIAL CHAOS
Authors: JUANG JONQ , SHIEH SHIH-FENG , TURYN LARRY
Published: September 2002

We consider a Cellular Neural Network (CNN) with a bias term in the integer lattice tenpoint ℤ2 on the plane tenpoint ℤ2. We impose a space-dependent coupling (template) appropriate for CNN in the hexagonal lattice on tenpoint ℤ2. Stable mosaic patterns of such CNN are completely characterized. The spatial entropy of a tenpoint (p1, p2)-translation invariant set is proved to be well-defined and exists. Using such a theorem, we are also able to address the complexities of resulting mosaic patterns.
SYNCHRONIZATION OF SWITCH DYNAMICAL SYSTEMS
Authors: DANCA MARIUS-F.
Published: September 2002

The well known synchronization method of Fujisaka and Yamada is adapted to a particular class of piecewise continuous dynamical systems. We give sufficient conditions for the underlying initial value problems, in order to define dynamical systems. For this purpose the Filippov regularization is used, the discontinuous initial value problem being switched into a differential inclusion. A generalized derivative for the considered class of functions is introduced.
Automatic Labeling of Semantic Roles
Authors: Gildea Daniel , Jurafsky Daniel
Published: September 2002

We present a system for identifying the semantic relationships, or semantic roles, filled by constituents of a sentence within a semantic frame. Given an input sentence and a target word and frame, the system labels constituents with either abstract semantic roles, such as Agent or Patient, or more domain-specific semantic roles, such as Speaker, Message, and Topic.

The system is based on statistical classifiers trained on roughly 50,000 sentences that were hand-annotated with semantic roles by the FrameNet semantic labeling project. We then parsed each training sentence into a syntactic tree and extracted various lexical and syntactic features, including the phrase type of each constituent, its grammatical function, and its position in the sentence. These features were combined with knowledge of the predicate verb, noun, or adjective, as well as information such as the prior probabilities of various combinations of semantic roles. We used various lexical clustering algorithms to generalize across possible fillers of roles. Test sentences were parsed, were annotated with these features, and were then passed through the classifiers.

Our system achieves 82% accuracy in identifying the semantic role of presegmented constituents. At the more difficult task of simultaneously segmenting constituents and identifying their semantic role, the system achieved 65% precision and 61% recall.

Our study also allowed us to compare the usefulness of different features and feature combination methods in the semantic role labeling task. We also explore the integration of role labeling with statistical syntactic parsing and attempt to generalize to predicates unseen in the training data.
Levodopa pharmacokinetic‐pharmacodynamic modeling and 6‐[18F]levodopa positron emission tomography in patients with Parkinson's disease
Authors: Dietz M. , Harder S. , Graff J. , Künig G. , Vontobel P. , Leenders K.L. , Baas H.
Published: August 2002

Objective

Parameters of a pharmacokinetic‐pharmacodynamic (PK‐PD) model of levodopa have been claimed to reflect the magnitude of the dopaminergic deficit in patients with Parkinson's disease. The aim of this study was to correlate such parameters with positron emission tomography (PET) with levodopa tagged with 6‐fluorine 18, an established imaging method for striatal dopaminergic neurons.

Methods

Twenty‐three patients in different disease stages (Hoehm and Yahr stage 2.5–5 [Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;4:427–42]; median duration, 12 years) were studied. PK‐PD modeling followed a single oral dose of levodopa/benserazide. The sum score of the Columbia Rating Scale (CURSΣ) was used for clinical assessments. A nonparametric effect compartment approach assuming a sigmoidal Emax model was applied to the PK‐PD analysis of plasma levodopa concentrations and corresponding CURSΣ. Thereafter 6‐[18F]levodopa PET was performed, and the influx rate constants (kc) for the putamen and the caudatus region were correlated with the median effective concentration (EC50) and the equilibrium half‐life (Teq) of the PK‐PD model.

Results

(1) A significant correlation was observed between PK‐PD parameters or with kc putamen as the dependent variable and the duration of the disease as the independent variable, which explains 33% of the variability of the EC50, 42% of the variability of Teq, and 36% of the variability of kc. (2) Significant correlations were observed between kc and either EC50 or Teq, yielding the closest correlation for the putamen region (r = −0.47, P < .05; and r = 0.55, P < .01; respectively).

Conclusions

Our findings show that key parameters of a PK‐PD model of levodopa were in fairly close agreement with imaging of dopaminergic neurons by 6‐[18F]levodopa PET. However, although PK‐PD modeling of levodopa has been proven as a useful investigation of approaches aimed to restore dopaminergic deficits or to monitor disease progression, this modeling cannot serve as a pathomorphologic surrogate for the loss of striatal dopaminergic neurons.

Clinical Pharmacology & Therapeutics (2001) 70, 33–41; doi: 10.1067/mcp.2001.116328
Prioritization of medical problems to improve adherence
Authors: Paul Simon
Published: August 2002

Clinical Pharmacology & Therapeutics (2002) 71, 211–213; doi: 10.1067/mcp.2002.122201
Cloak-and-Dagger Theory: Manifestations of the Mundane in the Space of Eight Peter Eisenman Houses
Authors: Major Mark David , Sarris Nicholas
Published: August 2002

In this paper we examine what appear to be the ‘rules’ of geometrical composition underlying the design of plan in eight well-known houses by Peter Eisenman. The effect of these compositional rules, tied to the design process of ‘decomposition’ described by Eisenman, in the generation of spatial layout in these houses is then analysed by using space syntax analysis. In particular, the effects of this design process in structuring the relationships, if any, between everyday living and ‘private’ household functions, that is, bedrooms, and the interface between inhabitants and visitors are examined. This is done in order to understand better the relationship, if any, between Eisenman's stated aims in his own theoretical writings about the design of these houses and the architectural object itself.
Self-Organized Settlements
Authors: Daffertshofer Andreas , Haken Hermann , Portugali Juval
Published: August 2002

In the present study we address the question of how persons or families occupy specific locations according to an attractiveness function between persons and flats. We suggest a mathematically formulated model in order to find optimal distributions of persons over flats. The model maximizes the global attractiveness of the ensemble and accounts for various conflicting situations. Its solutions show that, depending on initial conditions, both optimal as well as suboptimal configurations can be reached. An interpretation of the approach in terms of mental maps is offered.
On Binocular Alternation
Authors: Alais David , O'Shea Robert P , Mesana-Alais Corinne , Wilson Ian G
Published: August 2002

Diaz-Caneja (1928) made some prescient observations about binocular rivalry. Being in French, however, his paper remained largely unknown to the broader research community. His findings are similar to those reported very recently by contemporary researchers who had independently observed similar phenomena. Using concentric circles and parallel lines as stimuli, Diaz-Caneja presented half of each form to opposite eyes to provoke binocular rivalry. He observed periods in the ensuing binocular alternations in which rivalry occurred between the good Gestalt forms, despite the fact that they were distributed between the eyes. He proposed that each half of a good form generates synchronised oscillations in the visual system, and that this synchronisation enables the dichoptically viewed halves of the one form to be perceived as a whole.
Electrosynthesis Cell for X-Ray Absorption Fine Structure Measurement: Reduction of Air-Sensitive Iron-Sulfur Compounds
Authors: Bondin Mark I. , Foran Garry , Best Stephen P.
Published: August 2002

The design of a small-volume continuous-flow electrosynthesis cell, and its associated X-ray absorption fine structure (XAFS) cell, are reported. The extent of electrosynthesis of the solution used for collection of the XAFS data may be monitored, in line, by infrared (IR) or ultraviolet–visible (UV–vis) spectroscopy. The operation of the cell is demonstrated by the reduction of Fe2S2(CO)6 to the related dimer dianion, [Fe4S4(CO)12]2-. While the immediate coordination environment about the iron is similar for the two compounds, dimer formation results in an additional Fe–S interaction at 3.62 Å, which contributes to significant changes in the XAFS data in the region 10–12 Å-1. Analysis of the XAFS for the reduced species gave a full structural model which yielded a calculated multiple scattering (MS) XAFS pattern in good agreement with the data. Inclusion of the longer range Fe–Fe interactions (> 5 Å) did not give convergent fits within this formalism. These experiments demonstrate that ex situ electrosynthetic approaches provide an effective means of generating reactive species in a form suitable for XAFS examination.
On the distribution of gymnosperm genera, their areas of endemism and cladistic biogeography
Authors: Contreras-Medina Raúl , Vega Isolda Luna
Published: August 2002

A distributional analysis of 81 gymnosperm genera was undertaken. On the basis
of the congruence in the distribution of these genera, nine areas of endemism
were recognised. Many of these areas also represent areas of endemism for
other plant and animal taxa. South-western China and New Caledonia are
particularly interesting from the viewpoint of gymnosperm diversity and
endemism. The suggested areas of endemism agree in part with some floristic
regions previously proposed. The congruence between the areas of endemism
suggested and postulated Pleistocene refuges and panbiogeographic nodes is
discussed. A cladistic biogeographic analysis was carried out and a general
area cladogram obtained by strict consensus shows two major components, one
Gondwanic and the other almost Laurasian. This cladogram was compared with
previous studies and the similarities and differences among relationship areas
are discussed.
Historical taxonomy and a resolution of the Stylidium graminifolium complex (Stylidiaceae) in Tasmania
Authors: Jackson W. D. , Wiltshire R. J. E.
Published: August 2002

The troubled taxonomic history of
Stylidium graminifolium Sw. ex Willd. (syn.
Candollea serrulata Labill.) is reviewed. The entity
formerly known as S. graminifolium forms a complex
consisting of three species.
Stylidium graminifolium sens. str. is lectotypified on
the basis of plants collected by Banks and Solander from Botany Bay NSW in
1770. This narrow-linear-leaved species is diploid (2n
= 30) and is distributed widely on infertile soils in south-eastern
continental Australia and Tasmania. Stylidium armeria
Labill., on the basis of plants collected from southern Tasmania in the late
1790s, is a tetraploid (2n = 60), with leaves
about two to three or four times wider than in
S. graminifolium and more spathulate in shape. It has a
strictly littoral habitat along the rough water coasts of Tasmania from
Macquarie Heads to Tasman Peninsula, probably extending to the coasts of
south-eastern Australia. Stylidium melastachys R.Br., on
the basis of plants collected from the Kent Group in Bass Strait in 1803, is
synonymous with S. armeria. A third species,
S. dilatatum W.D.Jackson and R.J.E.Wiltshire, is
described as new. It is morphologically similar to
S. graminifolium but has linear leaves about two to
three times as wide as S. graminifolium and is a
tetraploid (2n = 60). It is widely distributed in
Tasmania and in the cooler subalpine areas of south-eastern Australia but is
confined to more fertile soils than the soils in which
S. graminifolium is found.
Heat content variation of interior Pacific Northwest conifer foliage
Authors: Williamson Nathan M. , Agee James K.
Published: August 2002

Heat content with and without ash was measured for foliage of three interior
Pacific Northwest conifers (Pinus ponderosa,
Pseudotsuga menziesii, and
Abies grandis/concolor) in five locations in Oregon
and Washington. Heat content with ash did not vary by species
(20.47–20.59 MJ kg–1), but ash content did
vary, so that heat content without ash varied by species. Heat content also
varied by location but, due to confounding with season, these differences
should be viewed with caution. Foliar heat content values averaged about
10% higher than those used for surface fuels in standard fire behavior
fuel models. If heat content is included in future models of crown fire
behavior, errors in using heat contents that are too low may have a larger
impact than most errors in estimating foliar moisture content, but sources of
error might be overwhelmed by other errors in estimating crown fire energy
balance.
Metabolic ecology of cockatoos in the south-west of Western Australia
Authors: Cooper C. E. , Withers P. C. , Mawson P. R. , Bradshaw S. D. , Prince J. , Roberston H.
Published: August 2002

This study examined the metabolic ecology of six cockatoo taxa endemic to the
south-west of Western Australia. As the availability of food is one factor
that may influence the abundance and distribution of these cockatoos, we
document here their baseline energy requirements and feeding patterns.
Evaporative waterloss was also measured as this may correlate with the aridity
of the species’ environment.
Basal metabolic rate was significantly lower at 0.62 ± 0.13 mL
O2 g–1
h–1 for the inland red-tailed black cockatoo than
1.11 ± 0.16 mL O2 g–1
h–1 for the forest red-tailed black cockatoo, but
there was no significant difference in metabolic rate between the two
white-tailed black cockatoos (0.86 ± 0.18 for Carnaby’s and 0.81
± 0.11 mL O2 g–1
h–1 for Baudin’s) or the two corellas (0.95
± 0.12 for Butler’s and 0.70 ± 0.04 mL
O2 g–1
h–1 for Muir’s). There were no significant
differences between the two white-tailed black cockatoos, and between the two
corellas, with respect to evaporative water loss. The inland red-tailed black
cockatoo had a significantly lower rate of evaporative water loss (0.44
± 0.07 mg g–1
h–1) than the forest red-tailed black cockatoo
(0.70 ± 0.06 mg g–1
h–1), which is presumably an adaptation to its
more arid habitat.
The total energy content of assorted native and introduced food items that
form significant proportions of the diets for these cockatoos varied from only
0.17 kJ for a 9-mg Emex australis seed to 63.9 kJ for a
3-g Banksia attenuata nut. The energy content of each
food item and the estimated daily energy requirements of the cockatoos enabled
the calculation of the numbers of nuts/cones/seeds required by each
species for a day, which ranged from 11 B. attenuata
nuts for a Carnaby’s cockatoo to 3592
Persoonia longifolia seeds for a forest red-tailed black
cockatoo.
DELTA DISTANCE AND VASSILIEV INVARIANTS OF KNOTS
Authors: YAMADA HARUMI
Published: August 2002

It is shown by Y. Ohyama, K. Taniyama and S. Yamada that for any natural number n and any knot K, there are infinitely many unknotting number one knots, whose Vassiliev invariants of order less than or equal to n coincide with those of K. We analyze it for delta unknotting number, and obtain the following. For any natural number n and any oriented knots K and M with a2(K)≠a2(M) there are infinitely many knots Jm such that the delta distance between Jm and M coincide with |a2(K)-a2(M)| and whose Vassiliev invariants of order less than or equal to n coincide with those of K. Here a2(K) is the second coefficient of the Conway polynomial of K.
CREATING HIGHLY RELIABLE MANUFACTURING SYSTEMS: AN INTEGRATED APPROACH
Authors: AZADEH M. ALI
Published: August 2002

The causes of complex manufacturing systems' failures are preliminarily analyzed. The techniques of creating highly reliable manufacturing systems are then discussed. It has been shown that modern safety and quality analysis conducted from early design phase to operation and maintenance will enhance the reliability of complex manufacturing systems. In addition, optimization between human operators and machines reduces confusion and increases the reliability of such systems. Employing teamwork in all aspects of the organizational systems will enhance the productivity of complex systems. Moreover, there should also exist a unique and systemic mechanism which integrates the performance of the organizational systems with those of technical (engineering) and nontechnical (people) subsystems.
OSTEOID OSTEOMA OF THE LUNATE — A CASE REPORT
Authors: Ayekoloye C. , Kumar A. , Lang D. M.
Published: August 2002

We report a rare case of an osteoid osteoma of the lunate bone in a young lady who presented to us with chronic wrist pain. She was treated by excision and cancellous bone grafting of the lesion with complete resolution of symptoms.
Pharmacogenetics, pharmacogenomics, and pharmacobiology
Authors: Kalow Werner
Published: August 2002

Clinical Pharmacology & Therapeutics (2001) 70, 1–4; doi: 10.1067/mcp.2001.116714
Fruit juices inhibit organic anion transporting polypeptide–mediated drug uptake to decrease the oral availability of fexofenadine
Authors: Dresser George K. , Bailey David G. , Leake Brenda F. , Schwarz Ute I. , Dawson Paul A. , Freeman David J. , Kim Richard B.
Published: August 2002

Objectives

Our objective was to examine the effect of different fruits and their constituents on P‐glycoprotein and organic anion transporting polypeptide (OATP) activities in vitro and on drug disposition in humans.

Methods

P‐glycoprotein–mediated digoxin or vinblastine efflux was determined in polarized epithelial cell monolayers. OATP‐mediated fexofenadine uptake was measured in a transfected cell line. The oral pharmacokinetics of 120 mg fexofenadine was assessed with water, 25%‐strength grapefruit juice, or normal‐strength grapefruit, orange, or apple juices (1.2 L over 3 hours) in a randomized 5‐way crossover study in 10 healthy subjects.

Results

Grapefruit juice and segments and apple juice at 5% of normal strength did not alter P‐glycoprotein activity. Grapefruit extract reduced transport. 6′,7′‐Dihydroxybergamottin had modest inhibitory activity (50% inhibitory concentration [IC50], 33 μmol/L). In contrast, grapefruit, orange, and apple juices at 5% of normal strength markedly reduced human OATP and rat oatp activity. 6′,7′‐Dihydroxybergamottin potently inhibited rat oatp3 and oatp1 (IC50, 0.28 μmol/L). Other furanocoumarins and bioflavonoids also reduced rat oatp3 activity. Grapefruit, orange, and apple juices decreased the fexofenadine area under the plasma concentration–time curve (AUC), the peak plasma drug concentration (Cmax), and the urinary excretion values to 30% to 40% of those with water, with no change in the time to reach Cmax, elimination half‐life, renal clearance, or urine volume in humans. Change in fexofenadine AUC with juice was variable among individuals and inversely dependent on value with water.

Conclusions

Fruit juices and constituents are more potent inhibitors of OATPs than P‐glycoprotein activities, which can reduce oral drug bioavailability. Results support a new model of intestinal drug absorption and mechanism of food‐drug interaction.

Clinical Pharmacology & Therapeutics (2002) 71, 11–20; doi: 10.1067/mcp.2002.121152
Pharmacokinetics of losartan and its metabolite E‐3174 in relation to the CYP2C9 genotype
Authors: Yasar Ümit , Forslund‐Bergengren Cecilia , Tybring Gunnel , Dorado Pedro , LLerena Adrián , Sjöqvist Folke , Eliasson Erik , Dahl Marja‐Liisa
Published: August 2002

Background And Aim

Losartan is metabolized by polymorphic CYP2C9 to E‐3174. Our aim was to evaluate the pharmacokinetics of losartan and E‐3174 in relation to the CYP2C9 genotype.

Methods

A 50‐mg oral dose of losartan was given to 22 Swedish volunteers with different CYP2C9 genotypes. Losartan and E‐3174 were analyzed by HPLC in plasma and urine samples collected up to 24 hours after drug intake. Furthermore, losartan and E‐3174 were analyzed in 8‐hour urine samples collected from 17 Spanish subjects after a single oral dose of 25 mg losartan.

Results

The maximum plasma concentration of E‐3174 was significantly (P < .05) lower in the CYP2C9*1/*3 (n = 5) and CYP2C9*2/*3 (n = 4) groups compared with the CYP2C9*1/*1 (n = 6) and CYP2C9*1/*2 (n = 3) groups and extremely low in 1 subject with the CYP2C9*3/*3 genotype. The ratio of the total losartan area under the plasma concentration–time curve (AUC) to the total E‐3174 AUC (AUClosartan/AUCE‐3174) was higher in the subject with the CYP2C9*3/*3 genotype (30‐fold) and also in the CYP2C9*1/*3 and *2/*3 groups (approximately 2‐ and 3‐fold, respectively) compared with the CYP2C9*1/*1 group. The plasma ratios correlated significantly with the 0‐ to 8‐hour urinary losartan/E‐3174 ratios. Among the total of 39 subjects, the urinary ratio was significantly higher in subjects with the CYP2C9*1/*3 (n = 10) and *2/*3 (n = 4) genotypes than in those with the CYP2C9*1/*1 genotype (n = 11; P < .01) and approximately 40‐fold higher in subjects with the CYP2C9*3/*3 genotype (n = 3).

Conclusion

The CYP2C9*3 allele was shown to be associated with decreased formation of E‐3174 from losartan. The significant differences between genotypes in plasma and urine losartan/E‐3174 ratios and the good correlation between the plasma and urine ratios suggest that the losartan/E‐3174 ratio in 0‐ to 8‐hour urine specimens may serve as a phenotyping assay for CYP2C9 activity. Further studies in larger populations will be required to establish this.

Clinical Pharmacology & Therapeutics (2002) 71, 89–98; doi: 10.1067/mcp.2002.121216
CYP3A4 variant alleles in white individuals with low CYP3A4 enzyme activity
Authors: García‐Martín Elena , Martínez Carmen , Pizarro Rosa M. , García‐Gamito Francisco J. , Gullsten Harriet , Raunio Hannu , Agúndez José A. G.
Published: August 2002

Objective

Our objective was to evaluate the presence of CYP3A4 gene variants in white individualswith low CYP3A4 enzyme activity.

Methods

Persons with extremely low enzyme activity, either in vitro or in vivo, were selected in a panel of 97 healthy subjects. Genetic analyses for CYP3A4 variant alleles present in white subjects, including CYP3A4*1B, CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*8, CYP3A4*11, CYP3A4*12, and CYP3A4*13, were performed on genomic deoxyribonucleic acid from these subjects by amplification‐restriction and sequencing.

Results

With the exception of CYP3A4*1B, none of the variant alleles analyzed were present in30 genes from persons with extremely low enzyme activity. CYP3A4*1B was present in the population studied with an allele frequency of 5.5%. Nevertheless, the presence of CYP3A4*1B does not correlate with low enzyme activity, either in vivo or in vitro, in either heterozygosity or homozygosity. CYP3A4*2 was not identified in 290 genes from Spanish persons or in 70 genes from Finnish persons.

Conclusions

Although the genetic component of the interindividual variability of CYP3A4 enzyme activity seems to be high, our findings do not support a key role for the variant alleles analyzed on the majority of white persons with low CYP3A4 activity. This suggests the occurrence of as yet unknown mutations that affect CYP3A4 orother functionally related genes.

Clinical Pharmacology & Therapeutics (2002) 71, 196–204; doi: 10.1067/mcp.2002.121371
The value of plasma acetaminophen half‐life in antidote‐treated acetaminophen overdosage
Authors: Schiødt Frank Vinholt , Ott Peter , Christensen Erik , Bondesen Stig
Published: August 2002

Background

A plasma acetaminophen (INN, paracetamol) half‐life of more than 4 hours has been correlated with hepatotoxicity in acetaminophen overdosing not treated with an antidote. Acetaminophen half‐life has not been studied in patients receiving the antidote N‐acetylcysteine.

Methods

Prospectively, 112 patients with acetaminophen overdosage all treated with intravenous N‐acetylcysteine were studied. A minimum of 2 plasma acetaminophen values >20 μmol/L were available for calculation of acetaminophen half‐life, assuming first‐order kinetics.

Results

Overall, the median acetaminophen half‐life was 5.4 hours (range, 0.8‐119.7 hours). Forty‐eight patients with no or little hepatotoxicity (ALT <1000 U/L), 43 patients with hepatotoxicity without encephalopathy, and 21 patients with hepatotoxicity and encephalopathy had acetaminophen half‐lives of 3.0 hours (range, 0.8‐10.0 hours), 6.4 hours (range, 1.3‐19.0 hours), and 18.4 hours (range, 4.6‐119.7 hours), respectively (P < .001). An acetaminophen half‐life >4 hours was observed in 71 patients, and 56 of those (79%) had hepatotoxicity(ALT >1000 U/L or coma). Thirty‐three of 41 patients (81%) with an acetaminophen half‐life <4 hours had no hepatotoxicity. A receiver operating characteristic curve analysis showed that an acetaminophen half‐life of 5.5 hours provided better discrimination; hepatotoxicity was therefore present in 49 of 54 patients with an acetaminophen half‐life >5.5 hours (positive predictive value, 91%) and in 15 of 58 patients with a half‐life below this limit (negative predictive value, 74%) despite treatment with N‐acetylcysteine.

Conclusions

Acetaminophen half‐life correlates well with the degree of liver damage in patients treated with the antidote N‐acetylcysteine. Longer half‐lives reflect a greater toxic effect on the liver.

Clinical Pharmacology & Therapeutics (2002) 71, 221–225; doi: 10.1067/mcp.2002.121857
Acute effect of L‐796568, a novel β3‐adrenergic receptor agonist, on energy expenditure in obese men
Authors: van Baak Marleen A. , Hul Gabby B. J. , Toubro Søren , Astrup Arne , Gottesdiener Keith M. , DeSmet Marina , Saris Wim H. M.
Published: August 2002

Objective

Our objective was to investigate the thermogenic efficacy of single oral doses of the novel β3‐adrenergic receptor agonist L‐796568 [(R)‐N‐[4‐[2‐[[2‐hydroxy‐2‐(3‐pyridinyl)ethyl]amino]ethyl]‐phenyl]‐4‐[4‐[4‐(trifluoromethyl)phenyl]thiazol‐2‐yl]‐benzenesulfonamide, dihydrochloride] inhumans.

Methods

Twelve healthy overweight to obese men participated in this 2‐center, 3‐period, randomized, placebo‐controlled, crossover trial. In each period subjects received 250 mg L‐796568, 1000 mg L‐796568, or placebo. Energy expenditure and respiratory quotient were determined by indirect calorimetry; blood samples were taken; and ear temperature, heart rate, and blood pressure were measured at baseline and during the 4‐hour period after administration.

Results

Energy expenditure increased significantly after the 1000‐mg dose (about 8%) and this was accompanied by an increase in plasma glycerol and free fatty acid concentrations. Systolic blood pressure also increased significantly. No changes in heart rate, diastolic blood pressure, ear temperature, plasma catecholamine, potassium, orleptin were found.

Conclusions

Single‐dose administration of 1000 mg of the novel β3‐adrenergic receptor agonist L‐796568 increased lipolysis and energy expenditure in overweight men. This is the first study to show such an effect of β3‐adrenergic receptor agonists in humans without significant evidence for β2‐adrenergic receptor involvement.

Clinical Pharmacology & Therapeutics (2002) 71, 272–279; doi: 10.1067/mcp.2002.122527
The Local Politics of Difference: An Examination of Intercommunal Relations Policy in Australian Local Government
Authors: Dunn Kevin , Hanna Bronwyn , Thompson Susan
Published: August 2002

A national survey of multicultural policy reveals that attempts by Australian local government to foster good intercommunal relations between cultural groups are poorly developed. Local government authorities (known as ‘councils’) limited their involvement to supporting festivals and information provision campaigns, often aimed at building Anglo-Celtic tolerance of other groups. Most community relations projects and policies were forms of exotic or assimilatory multiculturalism, rather than radical multiculturalism. Very few had developed policies to confront racism. Even those councils in areas with acknowledged interethnic discord were found to be reticient to intervene in local intercommunal relations. Some Australian councils celebrated and responded to the diversity of their citizenry. However, many failed to recognise heterogeneity and constructed certain minorities as a problematic ‘other’. Good local government practice involves the development of a comprehensive community relations policy. Such policy should be set within the wider context of recasting governance to encourage further involvement of the full range of local citizenry.
“This Land South Africa”: Rewriting Time and Space in Postapartheid Poetry and Property
Authors: Lewis Simon
Published: August 2002

The widespread concern in recent South African poetry with landscape and the question of what place the poet occupies in that landscape arises less as a response to the turn of the millennium than to the historical end of formal apartheid, but nonetheless marks an epochal shift in sensibility. Whereas much poetry of the 1980s evoked a sense of extreme dislocation in recent time and local space (marked by references to a precarious present of forced removal and migrancy, and unspecified, unsettled futures), some significant recent work has been marked by a desire to relocate the human presence in South Africa in terms of geological time and continental space. This generalization needs to be qualified by reference to racial and political positioning within South Africa, and in this paper I distinguish between the work of committed white writers such as ex-political-prisoner Jeremy Cronin (now Secretary of the South African Communist Party) and Barry Feinberg (now curator of the Mayibuye Centre), and the work of black writers such as Don Mattera, Seitlhamo Motsapi, Lesego Rampolokeng, and Daniel P Kunene. The regrounding of the human presence in South Africa by white writers such as Cronin and Feinberg attempts a radical remapping of South African cultural identity in utopianly unraced terms, while the reclamation of continental African and local South African place names by black writers such as Mattera, Motsapi, Rampolokeng, and Kunene draws attention to the material reality of a postapartheid heterotopia in which South Africa's postmodern landscape is being divided up and sold off in ways that combine a very old-fashioned rhetoric of class and space with a new/old racial coding.
Calibration of Cellular Automata by Using Neural Networks for the Simulation of Complex Urban Systems
Authors: Li Xia , Yeh Anthony Gar-On
Published: August 2002

This paper presents a new cellular automata (CA) model which uses artificial neural networks for both calibration and simulation. A critical issue for urban CA simulation is how to determine parameter values and define model structures. The simulation of real cities involves the use of many variables and parameters. The calibration of CA models is very difficult when there is a large set of parameters. In the proposed model, most of the parameter values for CA simulation are automatically determined by the training of artificial neural networks. The parameter values from the training are then imported into the CA model which is also based on the algorithm of neural networks. With the use of neural networks, users do not need to provide detailed transition rules which are difficult to define. The study shows that the model has better accuracy than traditional CA models in the simulation of nonlinear complex urban systems.
Housing Provision under Globalisation: A Case Study of Shanghai
Authors: Wu Fulong
Published: August 2002

Housing provision in China has undergone significant changes since economic reform. In the early stage of reform the objective was to solve the problems that are internal to the socialist economy, namely unrecoverable housing investment and housing shortages. The state adopted policies to ‘commodify’ and ‘decentralise’ housing provision. The mode of provision was transformed from a centrally allocated budget to shared investment contributed by state work-units, local governments, and individual households. Since the 1990s Chinese cities have seen increased foreign investment in real estate development and consequently experienced an unprecedented building boom. Little is know about the impacts of globalisation on housing development. The purpose of this paper is to examine the changes in housing investment and to highlight the dilemma of housing ‘commodification’ in the process of globalisation. Specifically, foreign investment contributed to initial capital formation in real estate development and more importantly helped to create a marketised housing segment. The buoyant market price demonstrated the profitability of real estate, thus attracting more capital into housing development. The combined effect of marketisation and globalisation has led to increasing social spatial differentiation and inadequate housing provision to marginal social groups.
Socialization and Residence: Ethnic Return Migrants in Estonia
Authors: Kulu Hill
Published: August 2002

In this paper I study the choice of residence of ethnic Estonians from the Soviet Union in Estonia. The aim is to clarify the extent to which the differences in the current residence of ethnic return migrants stem from their childhood growth environment. First, the groups of foreign-born Estonians are compared based on 1989 Soviet census data. The ethnic return migrants' place of residence is significantly related to their level of education and language skills: two variables corresponding to their previous residence, migration experience, and generational belonging. Second, the survey data are used to measure how closely the return migrants' current level of education and language skills correspond to their early socialization environment. The parents' level of education and the language of childhood significantly impact upon the level of education and language skills that return migrants have today. However, the current differences in the level of education and language skills have also been influenced by their life environment in Estonia. Yet, even when the influence of the current life environment on these variables has been eliminated, the levels of education and language skills appear to be an important source of the differences in residence. Thus, the research supports the idea that an individual's earlier socialization environment has a critical impact on their choice of residence.