bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotopolog perturbation techniques for metabolic networks: Metabolic recycling of nutritional glucose inDrosophila melanogaster
Authors: Eisenreich Wolfgang , Ettenhuber Christian , Laupitz Ralf , Theus Cornelia , Bacher Adelbert
Published: April 2004

Drosophila melanogasterstrain Oregon-R*was grown on standard medium supplemented with [U-13C6]glucose. One to two days after hatching, flies were extracted with water. Glucose was isolated chromatographically from the extract and was analyzed by13C NMR spectroscopy. All13C signals of the isolated glucose were multiplets arising by13C13C coupling. Based on a comprehensive analysis of the coupling constants and heavy isotope shifts in glucose, the integrals of individual13C signal patterns afforded the concentrations of certain groups of13C isotopologs. These data were deconvoluted by a genetic algorithm affording the abundances of all single-labeled and of 15 multiply labeled isotopologs. Among the latter group, seven isotopologs were found at concentrations >0.1 mol % with [1,2-13C2]glucose as the most prominent species. The multiply13C-labeled glucose isotopologs are caused by metabolic remodeling of the proffered glucose via a complex network of catabolic and anabolic processes involving glycolysis and/or passage through the pentose phosphate, the Cori cycle and/or the citrate cycle. The perturbation method described can be adapted to a wide variety of experimental systems and isotope-labeled precursors.
Arabidopsis thaliana
has the enzymatic machinery for replicating representative viroid species of the family Pospiviroidae
Authors: Daròs José-Antonio , Flores Ricardo
Published: April 2004

Viroids, subviral noncoding RNAs, replicate, move, and incite diseases in plants. Viroids replicate through a rolling-circle mechanism in which oligomeric RNAs of one or both polarities are cleaved and ligated into the circular monomers. Attempts to transmit viroids to
Arabidopsis
have failed for unknown reasons. To tackle this question,
Arabidopsis
was transformed with cDNAs expressing dimeric (+) transcripts of representative species of the families Pospiviroidae and Avsunviroidae, which replicate in the nucleus and the chloroplast, respectively. Correct processing to the circular (+) monomers was always observed, demonstrating that
Arabidopsis
has the appropriate RNase and RNA ligase. Northern blot hybridization also revealed the multimeric (-) RNAs of
Citrus exocortis viroid
and
Hop stunt viroid
(HSVd) of the family Pospiviroidae, but not of
Avocado sunblotch viroid
of the family Avsunviroidae, showing that the first RNA-RNA transcription of the rolling-circle mechanism occurs in
Arabidopsis
for the two nuclear viroids and that their multimeric (-) RNAs remain unprocessed as in typical hosts. Moreover, transgenic
Arabidopsis
expressing HSVd dimeric (-) transcripts accumulated the circular (+) monomers, although at low levels, together with the unprocessed primary transcript that served as the template for the second RNA-RNA transcription. Agroinoculation of
Arabidopsis
with the dimeric (+)
Citrus exocortis viroid
, HSVd, and
Coleus blumei viroid 1
cDNAs showed that these viroids could not move to distal plant parts, in contrast with the situation observed in their experimental hosts. Therefore, deficiencies in movement or low replication appear to be the factors limiting infectivity of some viroids in
Arabidopsis
.
Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa
Authors: Akiyama Haruhiko , Chaboissier Marie-Christine , Behringer Richard R. , Rowitch David H. , Schedl Andreas , Epstein Jonathan A. , de Crombrugghe Benoit
Published: April 2004

Epithelial–mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial–mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation.
Sox9
is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions. In
Sox9
-null mutants, endocardial cushions are markedly hypoplastic. In these mutants, Nfatc1 is ectopically expressed and no longer restricted to endothelial cells. Further, Sox9-deficient endocardial mesenchymal cells fail to express
ErbB3
, which is required for endocardial cushion cell differentiation and proliferation. Our results reveal a succession of molecular steps in the pathway of endocardial cushion development. We propose that loss of Sox9 inhibits epithelial–mesenchymal transformation after delamination and initial migration, but before definitive mesenchymal transformation.
Demonstration of a low-energy on-pathway intermediate in a fast-folding protein by kinetics, protein engineering, and simulation
Authors: Jemth Per , Gianni Stefano , Day Ryan , Li Bin , Johnson Christopher M. , Daggett Valerie , Fersht Alan R.
Published: April 2004

It is controversial whether fast-folding proteins can form productive on-pathway intermediates that are more stable than the denatured state because noncovalent intermediates are usually evanescent. Here, we apply the classical criteria for the existence of intermediates: namely, the intermediates form and react rapidly enough to be on pathway and they can be isolated and characterized. The folding of the 71-residue, mainly α-helical FF domain from human HYPA/FBP11 fulfills these classical criteria, as was found for Im7. The FF domain folds in two phases, one on the μs and the other on the ms time scale. An engineered mutant folds only to a partly folded state, with some 20–40% of the native helical content. The kinetic properties of the mutant are identical to those found for the fast phase of the wild-type protein, and it is likely that the mutant folds just to the intermediate state. A full kinetic analysis of the folding of wild-type protein, using the amplitudes of its native and denatured states and the observed values for the mutant, rules out an off-pathway scheme but fits an on-pathway scheme, with a low energy intermediate that is modeled by the mutant. The experimental proof benchmarks a molecular dynamics method that identifies an obligatory intermediate observed in multiple simulations. The conformational space defining this intermediate is visited several times in the simulations, leading to high populations consistent with the presence of a low energy intermediate.
Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation
Authors: Lin Shiaw-Yih , Li Kaiyi , Stewart Grant S. , Elledge Stephen J.
Published: April 2004

Claspin is a homolog of Mrc1, a checkpoint protein required for the DNA replication checkpoint in yeast. In
Xenopus
, phosphorylated Claspin binds to xChk1 and regulates xChk1 activation in response to replication stress. In this study, we have shown that the human homolog of Claspin is required for resistance to multiple forms of genotoxic stress including UV, IR, and hydroxyurea. Phosphorylation of Claspin was found to depend on the ataxia telangiectasia mutated-Rad3 related (ATR) pathway. DNA damage induces the formation of a complex between Claspin and BRCA1, a second regulator of Chk1 activation. Claspin was found to control BRCA1 phosphorylation on serine 1524, a site whose phosphorylation is controlled by the ATR pathway. These results are consistent with a model in which ATR regulates Claspin phosphorylation in response to DNA damage and replication stress resulting in recruitment and phosphorylation of BRCA1. BRCA1 and Claspin then function to activate the tumor suppressor Chk1. Unexpectedly, we found that Claspin has a second, positive role in control of the cell cycle as Claspin overexpression increased cell proliferation. These results suggest that Claspin has properties of both a tumor suppressor and an oncogene.
Cdc50p, a Protein Required for Polarized Growth, Associates with the Drs2p P-Type ATPase Implicated in Phospholipid Translocation inSaccharomyces cerevisiae
Authors: Saito Koji , Fujimura-Kamada Konomi , Furuta Nobumichi , Kato Utako , Umeda Masato , Tanaka Kazuma
Published: April 2004

Cdc50p, a transmembrane protein localized to the late endosome, is required for polarized cell growth in yeast. Genetic studies suggest that CDC50 performs a function similar to DRS2, which encodes a P-type ATPase of the aminophospholipid translocase (APT) subfamily. At low temperatures, drs2Δ mutant cells exhibited depolarization of cortical actin patches and mislocalization of polarity regulators, such as Bni1p and Gic1p, in a manner similar to the cdc50Δ mutant. Both Cdc50p and Drs2p were localized to the trans-Golgi network and late endosome. Cdc50p was coimmunoprecipitated with Drs2p from membrane protein extracts. In cdc50Δ mutant cells, Drs2p resided on the endoplasmic reticulum (ER), whereas Cdc50p was found on the ER membrane in drs2Δ cells, suggesting that the association on the ER membrane is required for transport of the Cdc50p-Drs2p complex to the trans-Golgi network. Lem3/Ros3p, a homolog of Cdc50p, was coimmunoprecipitated with another APT, Dnf1p; Lem3p was required for exit of Dnf1p out of the ER. Both Cdc50p-Drs2p and Lem3p-Dnf1p were confined to the plasma membrane upon blockade of endocytosis, suggesting that these proteins cycle between the exocytic and endocytic pathways, likely performing redundant functions. Thus, phospholipid asymmetry plays an important role in the establishment of cell polarity; the Cdc50p/Lem3p family likely constitute potential subunits specific to unique P-type ATPases of the APT subfamily.
MathSBML: a package for manipulating SBML-based biological models
Authors: Shapiro Bruce E. , Hucka Michael , Finney Andrew , Doyle John
Published: April 2004

Summary: MathSBML is a Mathematica package designed for manipulating Systems Biology Markup Language (SBML) models. It converts SBML models into Mathematica data structures and provides a platform for manipulating and evaluating these models. Once a model is read by MathSBML, it is fully compatible with standard Mathematica functions such as NDSolve (a differential-algebraic equations solver). MathSBML also provides an application programming interface for viewing, manipulating, running numerical simulations; exporting SBML models; and converting SBML models in to other formats, such as XPP, HTML and FORTRAN. By accessing the full breadth of Mathematica functionality, MathSBML is fully extensible to SBML models of any size or complexity.

Availability: Open Source (LGPL) at http://www.sbml.org and http://www.sf.net/projects/sbml.

Supplementary information: Extensive online documentation is available at http://www.sbml.org/mathsbml.html. Additional examples are provided at http://www.sbml.org/software/mathsbml/bioinformatics-application-note
Effects of Subanesthetic Ketamine on Regional Cerebral Glucose Metabolism in Humans
Authors: Långsjö Jaakko W. , Salmi Elina , Kaisti Kaike K. , Aalto Sargo , Hinkka Susanna , Aantaa Riku , Oikonen Vesa , Viljanen Tapio , Kurki Timo , Silvanto Martti , Scheinin Harry
Published: April 2004

Background

The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ketamine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism.

Methods

18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level. In addition, voxel-based analysis was performed for the relative changes in rGMR using statistical parametric mapping.

Results

The mean +/- SD measured ketamine serum concentration was 326.4+/-86.3 ng/ml. The mean arterial pressure was slightly increased (maximally by 16.4%) during ketamine infusion (P < 0.001). Ketamine increased absolute rGMR significantly in most regions of interest studied. The greatest increases were detected in the thalamus (14.6+/-15.9%; P = 0.029) and in the frontal (13.6+/-13.1%; P = 0.011) and parietal cortices (13.1+/-11.2%; P = 0.007). Absolute rGMR was not decreased anywhere in the brain. The voxel-based analysis revealed relative rGMR increases in the frontal, temporal, and parietal cortices.

Conclusions

Global increases in rGMR seem to parallel ketamine-induced increases in cerebral blood flow detected in the authors' earlier study. Therefore, ketamine-induced disturbance of coupling between cerebral blood flow and metabolism is highly unlikely. The previously observed decrease in oxygen extraction fraction may be due to nonoxidative glucose metabolism during ketamine-induced increase in glutamate release.
Moderate Increase in Intraabdominal Pressure Attenuates Gastric Mucosal Oxygen Saturation in Patients Undergoing Laparoscopy
Authors: Schwarte Lothar A. , Scheeren Thomas W. L. , Lorenz Christel , De Bruyne Filip , Fournell Artur
Published: April 2004

Background

Perioperative disturbances of microvascular blood flow and oxygenation in the intestinal tract have been hypothesized to play an important role in development of the multiple organ dysfunction syndrome. Herein, increased intra-abdominal pressure (IAP) has been identified as a key factor in the initiation of the pathophysiologic cascade. The authors hypothesized that increasing the IAP by intraperitoneal insufflation of carbon dioxide attenuates microvascular oxygen saturation in gastric mucosa. They tested this hypothesis in a prospective, observational study in 16 patients scheduled to undergo elective diagnostic laparoscopy.

Methods

The authors continuously assessed microvascular oxygen saturation in gastric mucosa by reflectance spectrophotometry. Simultaneously systemic oxygen saturation, heart rate, arterial blood pressure, and ventilation-derived variables were measured noninvasively. During general anesthesia and controlled mechanical ventilation, baseline values were obtained. Thereafter, the IAP was increased to 8 and 12 mmHg, respectively, followed by a control period after desufflation.

Results

The increase in IAP from baseline to 8 mmHg decreased microvascular oxygen saturation in gastric mucosa from 69+/-7% (mean +/- SD) to 63+/-8% at 8 mmHg IAP (P <0.05), with a further significant reduction to 54+/-13% at 12 mmHg IAP (P <0.01). Microvascular oxygen saturation in gastric mucosa recovered rapidly to baseline level (66 +/- 10%) after release of increased IAP. In striking contrast to regional mucosal oxygen saturation, systemic oxygenation did not change with either of the interventions.

Conclusions

The results suggest that increasing intraabdominal pressure to moderate levels, commonly applied to induce a surgical pneumoperitoneum, decreases gastric mucosal oxygen saturation.
Cerebral Oxygen Extraction and Autoregulation during Extracorporeal Whole Body Hyperthermia in Humans
Authors: Cremer Olaf L. , Diephuis Jan C. , van Soest Hanneke , Vaessen Paul H. B. , Bruens Marcel G. J. , Hennis Pim J. , Kalkman Cor J.
Published: April 2004

Background

The effects of hyperthermia on the human brain are incompletely understood. This study assessed the effects of whole body hyperthermia on cerebral oxygen extraction and autoregulation in humans.

Methods

Nineteen patients with chronic hepatitis C virus infection, not responding to interferon treatment, were subjected to experimental therapy with extracorporeal whole body hyperthermia at 41.8 degrees C for 120 min under propofol anesthesia (23 sessions total). During treatment series A (13 sessions), end-tidal carbon dioxide was allowed to increase during heating. During series B (10 sessions), end-tidal carbon dioxide was maintained approximately constant. Cerebral oxygen extraction (arterial to jugular venous difference of oxygen content) and middle cerebral artery blood flow velocity were continuously measured. Cerebral pressure-flow autoregulation was assessed by static tests using phenylephrine infusion and by assessing the transient hyperemic response to carotid compression and release.

Results

For treatment series A, cerebral oxygen extraction decreased 2.2-fold and cerebral blood flow velocity increased 2.0-fold during heating. For series B, oxygen extraction decreased 1.6-fold and flow velocity increased 1.5-fold. Jugular venous oxygen saturation and lactate measurements did not indicate cerebral ischemia at any temperature. Static autoregulation test results indicated loss of cerebrovascular reactivity during hyperthermia for both series A and series B. The transient hyperemic response ratio did not decrease until the temperature reached approximately 40 degrees C. Per degree Celsius temperature increase, the transient hyperemic response ratio decreased 0.07 (95% confidence interval, 0.05-0.09; P = 0.000). This association remained after adjustment for variations in arterial partial pressure of carbon dioxide, mean arterial pressure, and propofol blood concentration.

Conclusion

Profound hyperthermia during propofol anesthesia is associated with decreased cerebral oxygen extraction, increased cerebral blood flow velocity, and impaired pressure-flow autoregulation, indicating transient partial vasoparalysis.
Endothelial Glycocalyx as an Additional Barrier Determining Extravasation of 6% Hydroxyethyl Starch or 5% Albumin Solutions in the Coronary Vascular Bed
Authors: Rehm Markus , Zahler Stefan , Lötsch Michael , Welsch Ulrich , Conzen Peter , Jacob Matthias , Becker Bernhard Friedrich
Published: April 2004

Background

The impact on the endothelial glycocalyx for the extravasation of colloidal infusion solutions has not been investigated sufficiently.

Methods

Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer in a Langendorff mode. Solutions of 0.9% saline, 5% albumin (70 kd), or 6% hydroxyethyl starch (200 kd) were infused into the coronary system for 20 min at a rate of one third of the coronary flow, also during reperfusion after 15 min of ischemia, and after enzymatic digestion of the endothelial glycocalyx by heparinase. Net coronary fluid filtration was assessed directly by measuring the formation of transudate on the epicardial surface, and solute extravasation was assessed by measuring albumin and hydroxyethyl starch in the coronary effluent and transudate. Hearts were perfusion fixed to visualize the endothelial glycocalyx using transmission electron microscopy.

Results

Only infusion of hydroxyethyl starch, not infusion of albumin, significantly decreased net coronary fluid filtration. Heparinase application without ischemia increased coronary leak by 25% but did not accelerate the passage of colloids. Ischemia alone did not alter permeability. However, there was a large (approximately +200%), transient (approximately 4 min) increase in permeability for water, albumin, and hydroxyethyl starch after ischemia with heparinase application. Also, histamine (10 m) only increased permeability after pretreatment of the hearts with heparinase. The thickness of the glycocalyx after colloid administration was 0.2-0.3 microm. No glycocalyx could be detected after application of heparinase.

Conclusion

The endothelial glycocalyx acts as a competent barrier for water and colloids. Only after its destruction do changes in endothelial morphology (postischemic reperfusion or histamine application) become effective determinants of coronary extravasation.
Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus
Authors: Chagot Benjamin , Escoubas Pierre , Villegas Elba , Bernard Cédric , Ferrat Gilles , Corzo Gerardo , Lazdunski Michel , Darbon Hervé
Published: April 2004

Animal toxins block voltage‐dependent potassium channels (Kv) either by occluding the conduction pore (pore blockers) or by modifying the channel gating properties (gating modifiers). Gating modifiers of Kv channels bind to four equivalent extracellular sites near the S3 and S4 segments, close to the voltage sensor. Phrixotoxins are gating modifiers that bind preferentially to the closed state of the channel and fold into the Inhibitory Cystine Knot structural motif. We have solved the solution structure of Phrixotoxin 1, a gating modifier of Kv4 potassium channels. Analysis of the molecular surface and the electrostatic anisotropy of Phrixotoxin 1 and of other toxins acting on voltage‐dependent potassium channels allowed us to propose a toxin interacting surface that encompasses both the surface from which the dipole moment emerges and a neighboring hydrophobic surface rich in aromatic residues.
An efficient system for high‐level expression and easy purification of authentic recombinant proteins
Authors: Catanzariti Ann‐Maree , Soboleva Tatiana A. , Jans David A. , Board Philip G. , Baker Rohan T.
Published: April 2004

Expression of recombinant proteins as fusions to the eukaryotic protein ubiquitin has been found to significantly increase the yield of unstable or poorly expressed proteins. The benefit of this technique is further enhanced by the availability of naturally occurring deubiquitylating enzymes, which remove ubiquitin from the fusion product. However, the versatility of the system has been constrained due to the lack of a robust, easily purified deubiquitylating enzyme. Here we report the development of an efficient expression system, utilizing the ubiquitin fusion technique, which allows convenient high yield and easy purification of authentic protein. An Escherichia coli vector (pHUE) was constructed for the expression of proteins as histidine‐tagged ubiquitin fusions, and a histidine‐tagged deubiquitylating enzyme to cleave these fusions was expressed and purified. The expression system was tested using several proteins varying in size and complexity. These results indicate that this procedure will be suitable for the expression and rapid purification of a broad range of proteins and peptides, and should be amenable to high‐throughput applications.
Molecular heterogeneity in two families with auditory pigmentary syndromes: the role of neuroimaging and genetic analysis in deafness
Authors: Shears D , Conlon H , Murakami T , Fukai K , Alles R , Trembath R , Bitner‐Glindzicz M
Published: April 2004

We report two cases in which the probands presented with deafness and a family history of a dominantly inherited auditory pigmentary syndrome, yet the cause of deafness in each proband was not associated with the pigmentary abnormalities but was a result of mutations in SLC26A4, the gene mutated in Pendred's syndrome. The first case is a young woman with congenital sensorineural hearing loss and a family history of piebaldism. Despite showing no pigmentary abnormalities, the proband was found to harbor the same KIT mutation as her relatives affected by piebaldism, as well as two mutations in the SLC26A4 gene. In the second case, 2‐year‐old identical twin boys born to deaf parents presented with congenital sensorineural deafness and an extensive maternal family history of Waardenburg's syndrome type I (WSI). Their father had recessively inherited deafness associated with dilated vestibular aqueducts and a clinical diagnosis of Pendred's syndrome was made in him, which was confirmed molecularly. As the twin boys did not have features of WSI, both the mother and children were tested for mutations in SLC26A4 which showed the mother to be a carrier of a single mutation and both boys to be compound heterozygotes, illustrating pseudodominant inheritance of the condition.
Extended Semantics and Optimization Algorithms for CP‐Networks
Authors: Brafman Ronen I. , Dimopoulos Yannis
Published: April 2004

Preference elicitation is a serious bottleneck in many decision support applications and agent specification tasks. Ceteris paribus (CP)‐nets were designed to make the process of preference elicitation simpler and more intuitive for lay users by graphically structuring a set of CP preference statements—preference statements that most people find natural and intuitive. Beside their usefulness in the process of preference elicitation, CP‐nets support efficient optimization algorithms that are crucial in most applications (e.g., the selection of the best action to execute or the best product configuration). In various contexts, CP‐nets with an underlying cyclic structure emerge naturally. Often, they are inconsistent according to the current semantics, and the user is required to revise them. In this paper, we show how optimization queries can be meaningfully answered in many “inconsistent” networks without troubling the user with requests for revisions. In addition, we describe a method for focusing the user's revision process when revisions are truly needed. In the process, we provide a formal semantics that justifies our approach and new techniques for computing optimal outcomes. Some of the methods we use are based on a reduction to the problem of computing stable models for nonmonotonic logic programs, and we explore this relationship closely.
Solution Generation with Qualitative Models of Preferences
Authors: Faltings Boi , Torrens Marc , Pu Pearl
Published: April 2004

We consider automated decision aids that help users select the best solution from a large set of options. For such tools to successfully accomplish their task, eliciting and representing users' decision preferences is a crucial task. It is usually too complex to get a complete and accurate model of their preferences, especially regarding the trade‐offs between different criteria.We consider decision aid tools where users specify their preferences qualitatively: they are only able to state the criteria they consider, but not the precise numerical utility functions. For each criterion, the tool provides a standardized numerical function that is fixed and identical for all users and used to compare solutions. To compensate for the imprecision of this qualitative model, we let the user choose among a displayed set of possibilities rather than a single optimal solution. We consider the probability of finding the most preferred solution as a function of the number of displayed possibilities and the number of preferences. We present a probabilistic analysis, empirical validation on randomly generated configuration problems and a commercial application. We provide mathematical principles for the design of the selection mechanism, guaranteeing that users are able to find the target solution.
Multi‐Agent Constraint Systems with Preferences: Efficiency, Solution Quality, and Privacy Loss
Authors: Franzin M. S. , Rossi F. , Freuder E. C. , Wallace R.
Published: April 2004

In this paper, we consider multi‐agent constraint systems with preferences, modeled as soft constraint systems in which variables and constraints are distributed among multiple autonomous agents. We assume that each agent can set some preferences over its local data, and we consider two different criteria for finding optimal global solutions: fuzzy and Pareto optimality. We propose a general graph‐based framework to describe the problem to be solved in its generic form. As a case study, we consider a distributed meeting scheduling problem where each agent has a pre‐existing schedule and the agents must decide on a common meeting that satisfies a given optimality condition. For this scenario we consider the topics of solution quality, search efficiency, and privacy loss, where the latter pertains to information about an agent's pre‐existing meetings and available time‐slots. We also develop and test strategies that trade efficiency for solution quality and strategies that minimize information exchange, including some that do not require inter‐agent comparisons of utilities. Our experimental results demonstrate some of the relations among solution quality, efficiency, and privacy loss, and provide useful hints on how to reach a tradeoff among these three factors. In this work, we show how soft constraint formalisms can be used to incorporate preferences into multi‐agent problem solving along with other facets of the problem, such as time and distance constraints. This work also shows that the notion of privacy loss can be made concrete so that it can be treated as a distinct, manipulable factor in the context of distributed decision making.
Are Children “Intuitive Theists”?
Authors: Kelemen Deborah
Published: April 2004

Separate bodies of research suggest that young children have a broad tendency to reason about natural phenomena in terms of purpose and an orientation toward intention-based accounts of the origins of natural entities. This article explores these results further by drawing together recent findings from various areas of cognitive developmental research to address the following question: Rather than being “artificialists” in Piagetian terms, are children “intuitive theists”—disposed to view natural phenomena as resulting from nonhuman design? A review of research on children's concepts of agency, imaginary companions, and understanding of artifacts suggests that by the time children are around 5 years of age, this description of them may have explanatory value and practical relevance.
Letter Binding and Invariant Recognition of Masked Words
Authors: Dehaene S. , Jobert A. , Naccache L. , Ciuciu P. , Poline J.-B. , Le Bihan D. , Cohen L.
Published: April 2004

Fluent readers recognize visual words across changes in case and retinal location, while maintaining a high sensitivity to the arrangement of letters. To evaluate the automaticity and functional anatomy of invariant word recognition, we measured brain activity during subliminal masked priming. By preceding target words with an unrelated prime, a repeated prime, or an anagram made of the same letters, we separated letter-level and whole-word codes. By changing the case and the retinal location of primes and targets, we evaluated the invariance of those codes. Our results indicate that an invariant binding of letters into words is achieved unconsciously through a series of increasingly invariant stages in the left occipito-temporal pathway.
Binding of Cu(II) or Zn(II) in a de novo designed triple‐stranded α‐helical coiled‐coil toward a prototype for a metalloenzyme
Authors: Kiyokawa T. , Kanaori K. , Tajima K. , Koike M. , Mizuno T. , Oku J.‐I. , Tanaka T.
Published: April 2004

Abstract:  We previously reported the IZ‐3adH peptide, which formed a triple‐stranded coiled‐coil after binding Ni(II), Cu(II), or Zn(II). In this paper, we report the peptide, IZ‐3aH, having a new metal binding specificity. The IZ‐3aH peptide was found to bind Cu(II) and Zn(II) and form a triple‐stranded coiled‐coil. However, it did not bind Ni(II). Metal ion titrations monitored by circular dichroism revealed that the dissociation constants, Kd were 9 μm for Zn(II) and 10 μm for Cu(II). The bound Cu(II) ion has a planar tetragonal geometry, where the coordination positions are three nitrogens of the His residues and one H2O.
Scaling Up Learning Models in Public Good Games
Authors: Arifovic Jasmina , Ledyard John
Published: April 2004

We study three learning rules (reinforcement learning (RL), experience weighted attraction learning (EWA), and individual evolutionary learning (IEL)) and how they perform in three different Groves–Ledyard mechanisms. We are interested in how well these learning rules duplicate human behavior in repeated games with a continuum of strategies. We find that RL does not do well, IEL does significantly better, as does EWA, but only if given a small discretized strategy space. We identify four main features a learning rule should have in order to stack up against humans in a minimal competency test: (1) the use of hypotheticals to create history, (2) the ability to focus only on what is important, (3) the ability to forget history when it is no longer important, and (4) the ability to try new things.
Adolescent Sexual Decision‐Making; An Integrative Review
Authors: Hulton Linda J.
Published: April 2004

Purpose

(1) The purpose of this integrative review was to summarize the present literature to identify factors associated with adolescent sexual decision‐making. Thirty‐eight salient research studies were selected as a basis of this review from the databases of Medline, CINAHL, and Psychinfo using the Cooper methodology (Cooper, 1982 [13]).

Conclusions

(2) Two categories of decision‐making were identified: 1) The research on factors related to the decisions that adolescents make to become sexually active or to abstain from sexual activity; 2) The research on factors related to contraceptive decision‐making. The most consistent findings were that the factors of gender differences, cognitive development, perception of benefits, parental influences, social influences, and sexual knowledge were important variables in the decision‐making processes of adolescents.

Implications

(3) Practice implications for nursing suggest that clinicians should assess adolescent sexual decision‐making in greater detail and address the social and psychological context in which sexual experiences occur. Nurses must be aware of the differences between adolescent and adult decision‐making processes and incorporate knowledge of growth and development into intervention strategies. Moreover, to the degree that adolescent sexual decision‐making proves to be less than rational, interventions designed to improve competent sexual decision‐making are needed.
A Synthesis of What We Know About the Use of Physical Restraints and Seclusion with Patients in Psychiatric and Acute Care Settings: 2003 Update
Authors: Bower Fay L. , McCullough Cynthia S. , Timmons Mae E.
Published: April 2004

Purpose

(1) This article is an update of the January 19, 2000, Volume 7, Number 2 article of the synthesis of research findings on the use of restraint and seclusion with patients in psychiatric and acute care settings.

Conclusions

(2) The little that is known about restraint/seclusion use with these populations is inconsistent. Attitudes and perceptions of patients, family, and staff differ. However, all patients had very negative feelings about both, whether they were restrained/secluded or observed by others who were not restrained. The reasons for restraint/seclusion use vary with no accurate use rate for either. What precipitates the use of restraint/seclusion also varies, but professionals claim they are necessary to prevent/treat violent or unruly behavior. Some believe seclusion/restraint is effective, but there is no empirical evidence to support this belief. Many less restrictive alternatives have been tested with varying outcomes. Several educational programs to help staff learn about different ways to handle violent/confused patients have been successful.

Implications

(3) Until more is known about restraint/seclusion use from prospective controlled research, the goal to use least restrictive methods must be pursued. More staff educational programs must be offered and the evaluation of alternatives to restraint/seclusion pursued. When seclusion/restraint is necessary, it should be used less arbitrarily, less frequently, and with less trauma. As the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and the Health Care Financing Administration (HCFA) have prescribed, “Seclusion and restraint must be a last resort, emergency response to a crisis situation that presents imminent risk of harm to the patient, staff, or others” (p. 25) [99A].
A comparison of the prevalence of fluorosis in 8‐year‐old children from seven European study sites using a standardized methodology
Authors: Cochran Judith A. , Ketley Clare E. , Árnadóttir Inga B. , Fernandes Barros , Koletsi‐Kounari Haroula , Oila Anna‐Maria , Van Loveren Cor , Whelton Helen P. , O'Mullane Denis M.
Published: April 2004

Abstract ‐  Objectives: The objectives of this study were to report on the prevalence of enamel opacities from seven European study sites using a standardized photographic method, and to investigate the importance of variables responsible for enamel fluorosis. Methods: The sample comprised a randomly selected group of 300 8‐year‐old children in each of the study areas. One examiner from each area was trained and calibrated in the use of a standardized photographic technique. Two transparencies were taken of each child's permanent maxillary central incisor teeth; one to represent the teeth ‘wet’ and one when the teeth had been allowed to dry out naturally for 105 s. The transparencies were viewed ‘blind’ by the author (JAC) and scored using the DDE and TF indices. Data relating to variables considered to be associated with enamel fluorosis were also collected. Results: The prevalence of diffuse opacities ranged from 61% in fluoridated Cork (Ireland) to 28% in Athens (Greece). The percentage of subjects with a TF score of three or more ranged from 4% in Cork and nonfluoridated Haarlem (the Netherlands) to zero in Oulu (Finland) and Athens. Fluoridated water and the prolonged use of fluoride tablets were found to be significant contributory factors to fluorosis. Conclusions: The prevalence of fluorosis was found to be highest in fluoridated Cork. The prolonged use of fluoride supplements was also found to be a significant risk indicator associated with fluorosis.
Parental perception of fluorosis among 8‐year‐old children living in three communities in Iceland, Ireland and England
Authors: Sigurjóns Halla , Cochran Judith A. , Ketley Clare E. , Holbrook W. Peter , Lennon Michael A. , O'Mullane Denis M.
Published: April 2004

Abstract ‐  Objectives: To assess the impact of enamel fluorosis in three of the communities examined in ‘Project FLINT’, it was decided to conduct a structured telephone interview with the parents of some of the children who took part in the study. Methods: Three communities involved in this project were able to conduct this investigation: Reykjavik (Iceland), Cork (Ireland) and Knowsley (England). The aim was to interview the parents of children with a range of Thylstrup and Fejerskov (TF) index grades selected from each participating centre with respect to the appearance of their child's permanent maxillary central incisors. Interviewers were blinded as to the TF grade of the subject. Results: Interviews were conducted with parents of 215 children: 69 with TF grade 0; 70 with TF grade 1; 60 with TF grade 2 and 16 with TF grade 3 or greater. There was a trend towards more parents being unhappy with the appearance of their child's teeth with increasing TF grade. However, the main reasons given by parents for being unhappy with the appearance of their child's teeth was tooth alignment followed by the more yellow colour of permanent compared with primary teeth. Only with a TF grade of 3 was any appreciable concern expressed about fluorosis. Conclusion: It would appear that there is a public awareness of both developmental defects and enamel fluorosis although this is not always expressed as dissatisfaction. Further research is required into the clinical impact of both fluorosis and other developmental defects of enamel.
Effects of scaling and root planing on the amounts of interleukin‐1 and interleukin‐1 receptor antagonist and the mRNA expression of interleukin‐1β in gingival crevicular fluid and gingival tissues
Authors: Yoshinari Nobuo , Kawase Hitoshi , Mitani Akio , Ito Masamitsu , Sugiishi Shin , Matsuoka Masanori , Shirozu Norimitsu , Ishihara Yuichi , Bito Boku , Hiraga Makoto , Arakawa Kyoko , Noguchi Toshihide
Published: April 2004

Objective:  The purpose of this study was to evaluate the relationship between the clinical changes after non‐surgical periodontal therapy and interleukin 1 (IL‐1) in gingival crevicular fluid (GCF) and gingival tissues from patients with chronic periodontitis.

Background:  The inflammatory responses mediated by IL‐1 play an important role in periodontal tissue destruction. Although numerous studies have attempted to elucidate the dynamic movement involved in chronic periodontitis, the results have often conflicted. Such discrepancies may have been due to the inability to determine clinical disease activity.

Methods:  Seven patients with chronic periodontitis were examined. The severity of periodontal inflammation was expressed using clinical parameters before and after a scaling and root planing (SRP) procedure. The amounts and concentrations of IL‐1α, IL‐1β and IL‐1 receptor antagonist in GCF were measured by enzyme‐linked immunosorbent assay (ELISA) and IL‐1 activity index was calculated. A needle biopsy in matching gingival tissues was also performed before and after the SRP procedure. The localization and mRNA expression of IL‐1β were determined using histological methods.

Results:  Clinical parameters improved slightly after the SRP procedure. Only the probing pocket depth (PPD) was reduced significantly (p < 0.05). However, the amount of IL‐1β in GCF was slightly increased. The localization and mRNA expression of IL‐1β could still be observed after the SRP procedure. Therefore, none of the clinical parameters showed a high sensitivity or specificity for evaluating subgingival inflammation.

Conclusion:  These observations suggest that IL‐1 is effective for evaluating in detail the state of subgingival inflammation.
Accelerated alveolar bone loss in mice lacking interleukin‐10: late onset
Authors: Al‐Rasheed Abdulaziz , Scheerens Heleen , Srivastava Apurva K. , Rennick Donna M. , Tatakis Dimitris N.
Published: April 2004

Objective and background:  Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine regulating immune responses. We have previously reported that IL‐10(–/–) mice experience accelerated alveolar bone loss. The purpose of the present study was to examine the timing of the manifestation of accelerated alveolar bone loss in IL‐10(–/–) mice.

Materials and methods:  Twenty‐four IL‐10(–/–) and 21 IL‐10(+/+) age‐matched male 129/SvEv mice were used. Sacrifice times occurred at 1, 3 and 9.5 months of age. Alveolar bone loss was determined morphometrically on defleshed jaws. Enzyme‐linked immunosorbent assay (ELISA) was used for determination of serum concentration of type I collagen C‐telopeptide, a systemic marker of bone resorption.

Results:  Alveolar bone loss for the entire IL‐10(–/–) group was significantly different than for the IL‐10(+/+) group (p = 0.025). There was no significant difference in alveolar bone loss between IL‐10(–/–) and IL‐10(+/+) mice at 1 and 3 months of age. At 9.5 months of age, IL‐10(–/–) mice exhibited 39% greater alveolar bone loss than IL‐10(+/+) mice (p = 0.018). For IL‐10(–/–) mice, alveolar bone loss significantly increased with age. Serum C‐telopeptide levels significantly decreased with age in both groups. IL‐10(–/–) mice had consistently higher C‐telopeptide levels than IL‐10(+/+) mice and the difference between the two groups reached statistical significance (p = 0.011) for the 9.5‐month‐old mice.

Conclusions:  These results suggest that the accelerated alveolar bone loss observed in IL‐10(–/–) mice is a late‐onset condition and that lack of IL‐10 may have an effect on bone homeostasis.
HIV/AIDS and Urbanization
Authors: Dyson Tim
Published: April 2004

It is well known that levels of HIV prevalence tend to be appreciably higher inurban areas. This article considers the reasons for this and shows that within world regions that are relatively homogeneous with respect to their experience of HIV/AIDS, variation in the level of urbanization corresponds to about one‐third of variation in estimated HIV prevalence. Furthermore, for populations in the world's worst‐affected area—eastern and southern Africa—there are signs that, partly by differentially raising urban death rates and depressing urban birth rates, HIV/AIDS is slowing the pace of urbanization. Finally, in countries with very high levels of HIV infection and relatively low birth rates, such as in South Africa, the urban sector will soon constitute a “demographic sink”—with death rates exceeding birth rates.
New Estimates and Projections of Population Growth in Pakistan
Authors: Feeney Griffith , Alam Iqbal
Published: April 2004

Pakistan's population growth rate rose steadily from about 2.6 percent per annum in the early 1960s to a high of about 3.5 percent during the late 1980s. Since then it has declined to an estimated 2.1 percent for 2003. Growth rates calculated from the population censuses, which show a very different picture, are distorted by differential accuracy of enumeration. During the period of rising growth rates, fertility was constant at just under 7 children per woman while life expectancy at birth rose by nearly 20 years. Fertility decline began in the late 1980s, bringing the population growth rate down with it. Remarkably, there appears to have been little change in life expectancy over the past 15 years.
Fertility and Distorted Sex Ratios in a Rural Chinese County: Culture, State, and Policy
Authors: Murphy Rachel
Published: April 2004

This article explores how gender bias in population policies interacts with local culture to reinforce distortions in sex ratios among infants and young children in rural China. It argues that population policies introduce new sources of inequality into local culture while, conversely, gender inequalities embedded in local culture influence formal population policy and practice. Applying an institutional approach to the study of an agricultural county in Jiangxi province, southeast China, the analysis identifies four ways in which an interplay between gender bias in policy and culture produces gendered fertility outcomes: (1) the creation of gendered official categories such as “daughter‐only households”; (2) a male bias embedded in local government; (3) the use of local gender norms in state pedagogy; and (4) the reworking or subverting of official norms in ways that reinforce gender inequalities in local reproductive culture. The article concludes that despite indications of contestation of village patriarchy, discrimination against daughters is likely to persist.
Continuing the Family-Owned Home-Based Business: Evidence from a Panel Study
Authors: Winter Mary , Fitzgerald Margaret
Published: April 2004

A panel study of households in which someone is engaged in a home-based family business is analyzed to assess factors associated with the probability that the business will be operating three years later and reasons for quitting the business. Factors associated with the continuation of the business include age and education of the business owner, the number of years in business, positive feelings about the work, and expectations about changing attitudes toward the business. Neither income nor attitudes about income from the home-based work were significant predictors of the owner having the same business three years later.
Noren Discount Stores: Death of a Family Business
Authors: Goldberg Steven D.
Published: April 2004

This case is about a family-owned discount store chain that was unable to survive much beyond its founder. It tells the story of a first-generation American family and its struggle to grow and prosper in a family business during the early 1900s. The case takes the reader through the business' growth, maturity, decline, and, ultimately, its demise in 1991, which was brought about by issues such as organizational structure, the role of family in the family business, lack of succession planning, and myopic strategic planning. The author uses fictitious names, dates, and places to protect the surviving family members' privacy, and to ensure confidentiality.
Resolving Family Business Disputes Through Mediation
Authors: Haynes John M. , Usdin Thomas M. , Lee Begler Ann , Kaye Kenneth , Kaslow Florence
Published: April 2004

This first section is a collaborative piece that introduces a new format for Family Business Review. The first article discusses how mediation could be utilized in family-business disputes and includes a brief case study. The second set of articles is composed of invited commentary from three practitioners: an attorneyqmediator, a conflict specialist, and a psychologistqmediator. Then the authors provide a brief response to the commentary. The intent of this piece is to both educate and discuss the advantages and disadvantages of how mediation could effectively be used by family businesses to resolve conflict. We hope you enjoy the debate that ensues.