bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic obstructive pulmonary disease in never‐smoking animal farmers working inside confinement buildings
Authors: Monsó Eduard , Riu Elena , Radon Katja , Magarolas Ramon , Danuser Brigitta , Iversen Martin , Morera Josep , Nowak Dennis
Published: September 2004

Background

In animal farming, respiratory disease has been associated with indoor air contaminants and an excess in FEV1 decline. Our aim was to determine the characteristics and risk factors for chronic obstructive pulmonary disease (COPD) in never‐smoking European farmers working inside animal confinement buildings.

Methods

A sample of participants in the European Farmers' Study was selected for a cross‐sectional study assessing lung function and air contaminants. Dose–response relationships were assessed using logistic regression models.

Results

COPD was found in 18 of 105 farmers (45.1 SD 11.7 years) (17.1%); 8 cases (7.6%) with moderate and 3 cases (2.9%) with severe disease. Dust and endotoxin showed a dose–response relationship with COPD, with the highest prevalence of COPD in subjects with high dust (low = 7.9%/high = 31.6%) and endotoxin exposure (low = 10.5%/high = 20.0%). This association was statistically significant for dust in the multivariate analysis (OR 6.60, 95% CI 1.10–39.54).

Conclusion

COPD in never‐smoking animal farmers working inside confinement buildings is related to indoor dust exposure and may become severe. Am. J. Ind. Med. 46:357–362, 2004. © 2004 Wiley‐Liss, Inc.
Novel aspartyl proteinase associated to fat body histolysis during Ceratitis capitata early metamorphosis
Authors: Rabossi Alejandro , Stoka Veronika , Puizdar Vida , Turk Vito , Quesada‐Allué Luis A.
Published: September 2004

During larva to adult transition, the larval fat body of the Medfly (Ceratitis capitata) progressively disintegrates to be replaced by the adult one, after imago ecdysis. Here we show that a temporal correlation exists among the microscopy images of fat body progressive disintegration, the activation of fat body lysosomes (as judged by acid phosphatase activity), and the activity of a novel fat body aspartyl proteinase. The enzyme was purified and partially characterized. This proteinase exhibited a wide range of acid isoforms with isoelectric points from 5.6 to 7.3, an optimum pH of 3.0 for hemoglobin digestion, and was completely inhibited by pepstatin A. The apparent molecular weight was estimated (42 ± 1 kDa) and the protein was characterized as N‐glycosylated, judging from affinity to Concanavalin A. From the biochemical characteristics, the enzyme that we called “Early Metamorphosis Aspartyl Proteinase” (EMAP) appears to be similar to mammalian Cathepsin D. However, the N‐terminal sequence of EMAP showed no similarity with any known animal Cathepsins and exhibited an important instability to neutral and alkaline pH. This feature seems to be a peculiar characteristic of insect aspartyl proteinases. The temporal activity profile of EMAP during metamorphosis correlated well with the microscopy images of fat body cell autolytic death. Our data support the notion that EMAP is a metamorphosis‐specific lysosomal proteinase, mostly expressed during larval fat body histolysis. Arch. Insect Biochem. Physiol. 57:51–67, 2004. © 2004 Wiley‐Liss, Inc.
Phosphorylation of Rab proteins from the brain of Bombyx mori
Authors: Uno Tomohide , Nakao Atsushi , Katsurauma Chisato
Published: September 2004

Rab proteins play fundamental roles in the regulation of membrane traffic. Previously, from the brain of Bombyx mori we isolated two cDNA clones (BRab1 and BRab14), each of which encoded a different member of Rab‐protein family and was expressed in Escherichia coli and purified using an affinity chromatography. In this study, one cDNA clone (BRab8) was isolated from a cDNA library from the brain of B. mori. The recombinant protein was expressed in E. coli and purified. Next, the phosphorylations of these three purified BRab proteins were examined, using mammalian protein kinases in vitro. Protein kinase C (PKC) phosphorylated BRab8 and BRab14 proteins. Protein kinase A faintly phosphorylated BRab8 and BRab14 proteins. Calcium/calmodulin‐dependent protein kinase faintly phosphorylated BRab8 protein. Next, brains of B. mori were dissected and homogenized. The homogenate showed a calcium‐dependent protein kinase activity of BRab8 and BRab14 proteins. So PKC from the brain of B. mori was partially purified by a sequence of chromatographies on DEAE‐Cellulofine and affinity chromatography. This PKC phosphorylated BRab8 and BRab14 proteins . These results suggest that the function of Rab proteins in the brain of B. mori is regulated by calcium‐dependent protein kinases. Arch. Insect Biochem. Physiol. 57:68–77, 2004. © 2004 Wiley‐Liss, Inc.
Disruption of pupariation and eclosion behavior in the flesh fly, Sarcophaga bullata Parker (Diptera: Sarcophagidae), by venom from the ectoparasitic wasp Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae)
Authors: Rivers David B. , Zdarek Jan , Denlinger David L.
Published: September 2004

The action of venom from the ectoparasitic wasp, Nasonia vitripennis, was monitored by examining alterations in patterned muscular movements characteristic of pupariation and eclosion behavior in the flesh fly, Sarcophaga bullata. Venom injected into larvae prior to pupariation caused a dose‐dependent delay in pupariation. Eventually, such larvae did pupariate, but puparia were abnormally formed. Barographic records revealed that all elements of pupariation behavior were present in venom‐injected larvae, but pupariation behavior was not well synchronized with tanning, thus implying that the venom caused disruption in the temporal organization of central motor programs. When larvae were ligated and injected with venom posterior to the ligature, no response was evident in the posterior region, suggesting that the venom does not directly stimulate muscles or neuromuscular junctions. Injection of exogenous ecdysteroid into venom‐injected larvae restored some elements of pupariation behavior, consistent with ecdysone's role in stimulating the release of anterior retraction factor and puparium tanning factor, two factors that are released from the CNS to regulate pupariation. When the venom was injected into newly emerged imagoes, the duration of extrication behavior was shortened, whereas all phases of post‐eclosion behavior were lengthened. These observations imply that the venom affects CNS centers that regulate the muscular systems engaged in extrication and post‐eclosion behavior. Arch. Insect Biochem. Physiol. 57:78–91, 2004. © 2004 Wiley‐Liss, Inc.
Bioavailability of divalproex extended‐release formulation relative to the divalproex delayed‐release formulation
Authors: Dutta Sandeep , Zhang Yiming
Published: September 2004

Divalproex sodium extended‐release tablet (divalproex‐ER) is a novel formulation of the conventional divalproex sodium delayed‐release tablet (divalproex). In five multiple‐dose studies in healthy subjects (n=82) and epilepsy patients (n=86) the estimates of divalproex‐ER/divalproex ratios for steady‐state 24 h valproic acid area under the curve (AUC) central values, maximum concentration (Cmax) central values and minimum concentration (Cmin) means had ranges of 0.77–0.97, 0.71–0.87 and 0.78–1.03, respectively. These studies used different divalproex regimens (two, three or four times daily) and meal conditions (fasting, low, medium and high calorie meals). Divalproex‐ER was administered once daily. A meta‐analysis of divalproex‐ER/divalproex relative bioavailability across five studies under different meal conditions and divalproex dosing frequencies was performed. This meta‐estimate of relative bioavailability was used to provide dosing recommendations for conversion of patients from divalproex to divalproex‐ER. The estimatedAUC,CmaxandCmindivalproex‐ER/divalproex ratios (95% confidence interval) were 0.89 (0.85–0.94), 0.79 (0.74–0.84) and 0.96 (0.90–1.02), respectively. The food and divalproex regimen had no effect on the relative bioavailability. While switching from divalproex to divalproex‐ER, the divalproex‐ER daily dose may have to be increased by an average of 12% (calculated as 1.0/0.89) to achieve comparable plasma exposure. Since the divalproex‐ER dosage strengths (250 and 500 mg) are not 12% higher than the divalproex dosage strengths (125, 250 and 500 mg), an 8% to 20% higher divalproex‐ER daily dose should be considered for conversion from divalproex to divalproex‐ER. Copyright © 2004 John Wiley & Sons, Ltd.
Comparison of the bioavailability of 250 and 500 mg divalproex sodium extended‐release tablets in healthy volunteers
Authors: Dutta Sandeep , Zhang Yiming , Lee Lillian L. , O'Dea Robert
Published: September 2004

Divalproex sodium extended‐release tablet (divalproex‐ER), 500 mg strength, is approved for use in the prophylaxis of migraine headaches and epilepsy. The bioavailability of novel 250 mg divalproex‐ER formulations, under development to allow greater flexibility in dosing, was compared with the available 500 mg divalproex‐ER in a single‐dose, fasting and nonfasting, randomized, open‐label, crossover study in healthy adult volunteers. One group of 15 subjects was dosed after a 10 h overnight fast and another group of 24 subjects was dosed after a high‐fat breakfast. Plasma valproic acid concentration‐time profiles were used to assess pharmacokinetics. Bioequivalence assessments were made via the 90% confidence interval for maximum plasma valproic acid concentration (Cmax) and the area under the concentration‐time curve from time zero to infinity (AUC∞). The relative bioavailability point estimates (90% confidence interval) for Cmax and AUC∞ were 1.05 (0.94–1.16) and 0.95 (0.83–1.09) under fasting conditions, and 1.01 (0.91–1.12) and 0.97 (0.87–1.08) under nonfasting conditions, respectively. The test 250 mg tablet formulation was bioequivalent to the reference 500 mg tablet formulation, under both fasting and nonfasting conditions, as the 90% confidence intervals for both Cmax and AUC∞ were within the 0.80–1.25 interval. Copyright © 2004 John Wiley & Sons, Ltd.
Heterologous desensitization of insulin secretion by GIP (glucose‐dependent insulinotropic peptide) in INS‐1 cells: the significance of Gαi2 and investigations on the mechanism involved
Authors: Rucha A. , Verspohl E. J.
Published: September 2004

Heterologous desensitization is a term that describes the observation that chronic exposure of a cell to an agonist attenuates its response to other agonists. To characterize the cellular mechanisms that might be responsible for heterologous desensitization in an insulin secretory cell system (INS‐1), we investigated the link between G‐protein αi2 level and insulin secretion as the biological effect after prolonged incubation with glucose‐dependent insulinotropic polypeptide (GIP). Persistent activation (8 h) of the GIP signalling pathway decreased the GLP (glucagon‐like peptide)‐1 dependent insulin secretion (specific radioimmunoassay) accompanied by an upregulation of G‐protein αi2 protein level to about 126% whereas G‐protein αi3 and αs protein levels remained unchanged (assessed by Western blots using specific antibodies). This was accompanied by similar changes in Gαi2 mRNA. By using either the CaM kinase II inhibitor KN‐62, the calcineurin inhibitor FK 506 or the protein kinase A (PKA) inhibitor Rp‐8‐Br‐cAMPS, the GIP‐mediated Gαi2 mRNA increase was fully reversed. Heterologous desensitization of GLP‐1‐dependent insulin secretion by pretreatment with GIP, however, was not inhibited by calcium/calmodulin‐dependent enzymes (using KN‐62 and FK 506), but only by suppressing the cAMP/PKA signalling pathway using Rp‐8‐Br‐cAMPS. The outcome is not disturbed by effects initiated by these compounds per se since an 8‐h preincubation of cells did not affect glucose‐induced insulin secretion. We, therefore, suggest that heterologous desensitization in INS‐1 cells may be mediated by Gαi2 changes but depend on the cAMP/PKA signalling pathway probably distant form the Gαi2 protein. Copyright © 2004 John Wiley & Sons, Ltd.
EP24.15 interacts with the angiotensin II type I receptor and bradykinin B2 receptor
Authors: Shivakumar Bangalore R. , Wang Zoufei , Hammond Timothy G. , Harris Raymond C.
Published: September 2004

The carboxyl‐terminal cytoplasmic domain of the angiotensin II type 1 receptor (AT1) is known to interact with several classes of intracellular proteins that may modulate receptor function. Employing yeast two‐hybrid screening of a human embryonic kidney cDNA library with the carboxyl‐terminal cytoplasmic domain of the AT1 receptor as a bait, we have isolated EP24.15 (EC 3.4.24.15, thimet oligopeptidase) as a potentially interacting protein. EP24.15 is widely distributed and is known to degrade bioactive peptides such as angiotensin I and II and bradykinin. In addition, EP24.15 was previously identified as a putative soluble angiotensin II binding protein. Two‐hybrid screening also determined that EP24.15 can interact with the B2 bradykinin receptor. Transient expression of EP24.15 in a porcine kidney epithelial cell line stably expressing full length AT1 and full length B2 followed by affinity chromatography and co‐immunoprecipitation confirmed EP24.15 association with both AT1 and B2 receptors. EP24.15 was also co‐immunoprecipitated with AT1 and B2 in rat kidney brush border membranes (BBM) and basolateral membranes (BLM). Both AT1 and B2 undergo ligand‐induced endocytosis. Analysis of endosomal fractions following immunoprecipitation with AT1 or B2 antibodies detected strong association of EP24.15 with the receptors in both light and heavy endosomal populations. Therefore, the present study indicates that EP24.15 associates with AT1 and B2 receptors both at the plasma membrane and after receptor internalization and suggests a possible mechanism for endosomal disposition of ligand that may facilitate receptor recycling. Copyright © 2004 John Wiley & Sons, Ltd.
Direct measurement of the passive stiffness of rat sperm and implications to the mechanism of the calcium response
Authors: Schmitz‐Lesich Kathleen A. , Lindemann Charles B.
Published: September 2004

Glass microprobes were used to measure the stiffness of the flagella of Triton X‐100‐extracted rat sperm models. The sperm models were treated with 50 μM sodium vanadate and 0.1 mM Mg‐ATP to evaluate the stiffness of the passive flagellar structure without the influence of the dynein motor proteins. The passive stiffness was determined to be 4.6 (± 1.1) × 10−19 N × m2. Rat sperm models exposed to greater than 10−5 M calcium ions exhibit a strong bend in the basal 40 μm of the flagellum, resulting in a fishhook‐like appearance. The torque required to bend a passive rat sperm flagellum into the fishhook‐like configuration was determined. The result was compared to the previously published measurement of the torque required to straighten the flagella of rat sperm in the Ca2+‐induced fishhook configuration [Moritz et al., 2001: Cell Motil. Cytoskeleton 49:33–40]. The torque required to induce a fishhook in a passive flagellum was 2.7 (± 0.7) × 10−14 N × m and the torque to straighten an active Ca2+‐induced fishhook was 2.6 (± 1.4) × 10−14 N × m. These values are identical within the limit of error of the measurement technique. This finding suggests that the fishhook configuration observed in the Ca2+ response of rat sperm is the result of a Newtonian equilibrium, where active torque produced by dynein is counterbalanced by an equal and opposite passive torque that results from bending the flagellum. Consistent with this mechanism, the Ca2+‐induced fishhook configuration is progressively relaxed by incremental increases in sodium vanadate concentration. This supports an active role of the dynein motors in producing the torque for the response. When rat sperm respond to Ca2+, the bend in the flagellum always forms in the direction opposite the curvature of the asymmetric sperm head. Based on this polarity, the bending torque for the Ca2+ response must result from the action of the dyneins on outer doublets 1 through 4. Cell Motil. Cytoskeleton 59:169–179, 2004. © 2004 Wiley‐Liss, Inc.
Molecular Origins of the Remarkable Chiral Sensitivity of Second‐Order Nonlinear Optics
Authors: Simpson Garth J.
Published: September 2004

Recent observations of remarkably large chiroptical effects in second‐harmonic generation (SHG) and sum‐frequency generation (SFG) measurements suggest exciting possibilities for the development of new chiral‐specific spectroscopies and novel chiral materials for nonlinear optics. Several fundamental studies designed to elucidate the molecular and macromolecular origins of the chiral responses are reviewed to provide a framework for development of this emerging field. In general, the chiral activity in SHG and SFG has the potential to arise from complex interactions between hosts of different competing effects. Fortunately, relatively simple electric dipole‐allowed mechanisms routinely dominate the nonlinear optical chiral activities of most practical systemsexpressions can often be generated to link the . This substantial reduction in complexity allows for the development of simple models connecting the macroscopic nonlinear optical response to intuitive molecular and supramolecular properties.
Photonic Crystals—A Step towards Integrated Circuits for Photonics
Authors: Thylén Lars , Qiu Min , Anand Srinivasan
Published: September 2004

The field of photonic crystals has, over the past few years, received dramatically increased attention. Photonic crystals are artificially engineered structures that exhibit a periodic variation in one, two, or three dimensions of the dielectric constant, with a period of the order of the pertinent light wavelength. Such structures in three dimensions should exhibit properties similar to solid‐state electronic crystals, such as bandgaps, in other words wavelength regions where light cannot propagate in any direction. By introducing defects into the periodic arrangement, the photonic crystals exhibit properties analogous to those of solid‐state crystals. The basic feature of a photonic bandgap was indeed experimentally demonstrated in the beginning of the 1990s, and sparked a large interest in, and in many ways revitalized, photonics research. There are several reasons for this attention. One is that photonic crystals, in their own right, offer a proliferation of challenging research tasks, involving a multitude of disciplines, such as electromagnetic theory, nanofabrication, semiconductor technology, materials science, biotechnology, to name a few. Another reason is given by the somewhat more down‐to‐earth expectations that photonics crystals will create unique opportunities for novel devices and applications, and contribute to solving some of the issues that have plagued photonics such as large physical sizes, comparatively low functionality, and high costs. Herein, we will treat some basics of photonic crystal structures and discuss the state‐of‐the‐art in fabrication as well give some examples of devices with unique properties, due to the use of photonic crystals. We will also point out some of the problems that still remain to be solved, and give a view on where photonic crystals currently stand.
Theoretical Study of the Reactions of CF3OCHF2 with the Hydroxyl Radical and the Chlorine Atom
Authors: Wu Jia‐yan , Liu Jing‐yao , Li Ze‐sheng , Sun Chia‐chung
Published: September 2004

Theoretical investigations are carried out on the reaction mechanism of the reactions of CF3OCHF2 (HFOC‐125) with the OH radicals and Cl atoms, as well as the heats of formation of CF3OCHF2 and CF3OCF2. The electronic structure information on the potential energy surface for each reaction is obtained at the B3LYP/6–311G(d,p) level, and energetic information is further refined by G3(MP2) theory. The direct dynamics calculation of the hydrogen abstraction reactions are also performed at the G3(MP2)//B3LYP/6–311G(d,p) level. The classical energy profile is corrected by interpolated single‐point energies (ISPE) approach, incorporating the small‐curvature tunnelling effect (SCT) calculated by the variational transition‐state theory (VTST). The rate constants are in good agreement with the experimental data and are found to be k1=4.95×10−30 T5.40 exp(−347/T) and k2=1.86×10−23 T3.43 exp(−1579/T) cm3 molecule−1 s−1 over the temperature range 200–2000 K. The rate constants at 298 K for these two reactions are 3.38×10−16 and 2.80×10−17 cm3 molecule−1 s−1, respectively. Using group‐balanced isodesmic reactions as working chemical reactions, the standard enthalpies of formation for CF3OCHF2 and CF3OCF2 are −312.3±1.0 and −257.3±1.0 kcal mol−1, respectively, evaluated by G3(MP2) theory based on the B3LYP/6–311G(d,p) geometries. The theoretical studies provide rate constants of the title reactions and the enthalpies of the species, which are important parameters in determining the atmospheric lifetime and the feasible pathways for the loss of HFOC‐125.
The Origin of Aromaticity: Important Role of the Sigma Framework in Benzene
Authors: Kovačević Borislav , Barić Danijela , Maksić Zvonimir B. , Müller Thomas
Published: September 2004

The physical nature of aromaticity is addressed at a high ab initio level. It is conclusively shown that the extrinsic aromatic stabilization energy of benzene E(ease)B, estimated relative to its linear polyene counterpart(s), is very well‐reproduced at the Hartree–Fock (HF) level. This is a consequence of the fact that the contributions arising from the zero‐point vibrational energy (ZPVE) and electron correlation are rather small. More specifically, they yield together 2.0 kcal mol−1 to the destabilization of benzene. A careful scrutiny of the HF energies by virial theorem shows further that the kinetic energies of the σ and π electrons E(T)${{{\sigma \hfill \atop HF\hfill}}}$ and E(T)${{{{\rm \pi} \hfill \atop HF\hfill}}}$ are strictly additive in the gauge linear zig‐zag polyenes, which also holds for their sum Et(T)HF. This finding has the important corollary that E(ease)B is little dependent on the choice of the homodesmic reactions involving zig‐zag polyenes. A detailed physical analysis of the σ‐ and π‐electron contributions to extrinsic aromaticity requires explicit introduction of the potential energy terms Vne, Vee, and Vnn, which signify Coulomb interactions between the electrons and the nuclei. The Vee term involves repulsive interaction V${{{{\rm \sigma} {\rm \pi} \hfill \atop ee\hfill}}}$ between the σ and π electrons, which cannot be unequivocally resolved into σ and π contributions. The same holds for the Vnn energy, which implicitly depends on the electron density distribution via the Born–Oppenheimer (BO) potential energy surface. Several possibilities for partitioning V${{{{\rm \sigma} {\rm \pi} \hfill \atop ee\hfill}}}$ and Vnn terms into σ and π components are examined. It is argued that the stockholder principle is the most realistic, which strongly indicates that E(ease)B is a result of favorable σ‐framework interactions. In contrast, the π‐electron framework prefers the open‐chain linear polyenes.
Quantum Dynamics Study of the Excited‐State Double‐Proton Transfer in 2,2′‐Bipyridyl‐3,3′‐diol
Authors: Gelabert Ricard , Moreno Miquel , Lluch José M.
Published: September 2004

Density functional theory and quantum dynamics simulations have been used to study the double‐proton transfer reaction in 2,2′‐bipyridyl‐3,3′‐diol in the first singlet excited electronic state. This process is experimentally known to be branched: It consists of a fast, concerted reaction mechanism (τ≈100 fs) and a stepwise reaction mechanism [with a fast initial step (τ≈100 fs) and a slower final step (τ≈10 ps)]. Quantum dynamics simulations on a two‐dimensional model reveal that the concerted reaction occurs despite the nonexistence of a concerted reaction path, but they fail to explain the relative slowness of the stepwise mechanism. A qualitative simulation using a three‐dimensional model suggests that internal vibrational relaxation (IVR) might be the reason why the second stage of the stepwise mechanism is so slow.
Local Dense Structural Heterogeneities in Liquid Water from Ambient to 300 MPa Pressure: Evidence for Multiple Liquid–Liquid Transitions
Authors: Khoshtariya Dimitri E. , Zahl Achim , Dolidze Tina D. , Neubrand Anton , van Eldik Rudi
Published: September 2004

Difference and double‐difference near‐infrared DO–D and HO–H stretching overtone (2νOD and 2νOH) spectroscopy and a rigorous (physically substantiated) band deconvolution technique were applied to reveal three different kinds of inherent (interstitial) structures of liquid water, which determine its high density (compared to ice Ih under ambient conditions), its compressibility (under hydrostatic pressure, up to 300 MPa), and its high fragility (manifested under temperature variation). Our data processing allowed the rigorous discrimination of up to six vibrational components. On the basis of an extensive comparative analysis combined with available structural data (X‐ray and neutron scattering) and molecular dynamics (MD) simulations for liquid water, as well as with experimental and computed data for small non‐tetrahedrally arranged water clusters, the major four components could be ascribed to: i) The basic Ih icelike substructure; ii) the temperature‐dependent remote interstitial “defects” due to tetrahedral displacements (primarily responsible for transport properties); iii) the interstitial “defects” most probably arranged in quasiplanar noncyclic tetramers (totally absent in the ice structure); and iv) the interstitial “defects” formed with increasing pressure, probably arranged in cubic water octamers and composed of two pairs of noncyclic and cyclic tetramer fragments. The latter structures include, essentially, bent hydrogen bonds stabilized by resonance effects.
A comparison of CBT and EMDR for sexually‐abused Iranian girls
Authors: Jaberghaderi Nasrin , Greenwald Ricky , Rubin Allen , Zand Shahin Oliaee , Dolatabadi Shiva
Published: September 2004

Fourteen randomly assigned Iranian girls ages 12–13 years who had been sexually abused received up to 12 sessions of CBT or EMDR treatment. Assessment of post‐traumatic stress symptoms and problem behaviours was completed at pre‐treatment and 2 weeks post‐treatment. Both treatments showed large effect sizes on the post‐traumatic symptom outcomes, and a medium effect size on the behaviour outcome, all statistically significant. A non‐significant trend on self‐reported post‐traumatic stress symptoms favoured EMDR over CBT. Treatment efficiency was calculated by dividing change scores by number of sessions; EMDR was significantly more efficient, with large effect sizes on each outcome. Limitations include small N, single therapist for each treatment condition, no independent verification of treatment fidelity, and no long‐term follow‐up. These findings suggest that both CBT and EMDR can help girls to recover from the effects of sexual abuse, and that structured trauma treatments can be applied to children in Iran. Copyright © 2004 John Wiley & Sons, Ltd
Treatment of flying phobia using virtual reality: data from a 1‐year follow‐up using a multiple baseline design
Authors: Botella C. , Osma J. , Garcia‐Palacios A. , Quero S. , Baños R.M.
Published: September 2004

The present work is a new contribution about the short‐ and long‐term efficacy of virtual reality (VR) exposure therapy for the treatment of flying phobia (FP). We present data from pre‐treatment, post‐treatment and 1‐year follow‐up assessments in a sample of nine participants using a multiple baseline design. The treatment programme included a main therapeutic component: VR exposure (six sessions), accompanied by one session of education about anxiety, flying and exposure. The VR software developed by our team is described. Our software included, besides the virtual scenario used by most researchers, the plane, two new scenarios: the room and the airport, developed to work with the patients anticipatory anxiety. The results obtained, at post‐treatment and 1 year after the completion of the treatment, support the efficacy of VR in the treatment of flying phobia. VR produced an activation of the fear and avoidance structures and a progressive decrement of fear, avoidance and belief in catastrophic thoughts. The scores in other specific self‐report meaures of flying phobia confirm these findings. After the treatment, all participants flew. Our data support the efficacy of VR for the treatment of flying phobia achieved by other studies. Our contribution to this field is the use of VR exposure as the only therapeutic component, the long‐term efficacy data, and the use of VR software for the treatment of anticipatory anxiety. Copyright © 2004 John Wiley & Sons, Ltd.
Effects of control loop delay on the stability of a rate control algorithm
Authors: Aweya James , Montuno Delfin Y. , Ouellette Michel
Published: September 2004

This paper presents exact stability analysis of a rate control algorithm described inPerform. Eval.2001;43(2–3):63–94;Int. J. Commun. Systems2001;14(6):593–618. The stability regions of the rate control process in the presence of control loop delay are analysed. The rate control process is represented by delay‐difference equation and the criteria for asymptotic stability are derived in terms of the control parameters and control loop delay. The analysis shows that the approximate upper bound of the control gain derived in Aweyaet al.is very close to the exact bound developed here. Using theoretical calculations performed in the discrete‐time domain, we show that as the feedback time delaydincreases, the intensity of control (i.e. the control gain α) must decrease in order for the system to remain stable. Copyright © 2004 John Wiley & Sons, Ltd.
Price partitioning on the Internet
Authors: Xia Lan , Monroe Kent B.
Published: September 2004

The Internet provides managers with opportunities to monitor and manage their pricing strategies and tactics with minimum costs. Partitioning the total product sale price into a base price and various surcharges, such as shipping and handling, taxes, and other fees, is one way to manage price structures online. Using three experiments, our research shows that appropriate online price partitioning may enhance consumers’ purchase intentions, perceived value, and price satisfaction, and reduce further information search intentions. The effect of price partitioning is due to both consumers’ insufficiently adjusting for the surcharge and the clarity of the price structure provided. However, when multiple surcharges are added to partition the price further, these positive effects may decline leading to an inverted “U” shape function of partitioning on price perceptions. Finally, the amount and the way the surcharges are presented are important factors to consider when designing an effective price partitioning structure.
Seller rating, price, and default in online auctions
Authors: Bruce Norris , Haruvy Ernan , Rao Ram
Published: September 2004

Whereas in brick and mortar stores quality and seller reliability can be effectively communicated through a variety of quality cues, in the online world different mechanisms help sellers establish reputation and trust. Among the commonly used mechanisms by infomediaries that screen and rate sellers are customer-feedback reputation mechanisms where buyers provide seller ratings and feedback. The success of such mechanisms and their impact on prices in electronic markets are described and empirically investigated in this work. Specifically, we investigate both theoretically and empirically (1) whether seller ratings affect consumer valuations, particularly in the presence of insurance; (2) whether seller ratings are indicative of future default likelihood; and (3) whether a seller who is terminal (about to go out of business) is more likely to default prior to exiting.
Price communications in online and print coupons: An empirical investigation
Authors: Suri Rajneesh , Swaminathan Srinivasan , Monroe Kent B.
Published: September 2004

Online and print coupons use different media to communicate price information and, hence, are likely to be processed differently. This research suggests that the evaluation of coupons is a function of the interaction between consumers’ motivation to process information and the type of medium used to present the coupon. Using two different prices (high vs. low), the results show that motivated consumers are likely to process information in a print coupon more carefully than in an online coupon. Less motivated consumers, however, are likely to process information in an online coupon more carefully than that in a print coupon.
The effects of buyer identification and purchase timing on consumers’ perceptions of trust, price fairness, and repurchase intentions
Authors: Grewal Dhruv , Hardesty David M. , Iyer Gopalkrishnan R.
Published: September 2004

The ease of use and commercial feasibility of Internet-enabled technologies for price segmentation have found increased managerial applications as well as a concurrent rise in questions about fairness and legality. We examine the role of two price segmentation tactics and assess their effects on consumer perceptions of trust, fairness of the price differences, and repurchase intentions using two studies. We find that consumers report lower levels of trust, price fairness, and repurchase intentions when Internet-enabled buyer identification techniques are used (as compared to purchase timing tactics) to segment consumer markets. Our experimental results also suggest that the difference between these two tactics is more pronounced when firms do not provide an explanation for the price differences. The results also indicate that the size of the price difference has a significant effect on trust, fairness, and willingness to buy.
Introduction to the special issue on online pricing
Authors: Jap Sandy D. , Naik Prasad A.
Published: September 2004

Interactive marketing now exceeds a trillion dollars in sales and is growing at 10% per annum ( www.census.gov/estats ). The growth in online transactional activity raises a fundamental question: Is there anything really different about the theory or practice of pricing strategies online versus off-line? In other words, do pricing phenomena change simply because transactions have migrated from stores and catalogues to computer-mediated interfaces? Can pricing theory and strategies remain invariant regardless of whether firms post prices online or off-line and regardless of whether customers access and respond to prices online or off-line? This special issue provides insights into these questions by examining a wide variety of online pricing phenomena. Top scholars in the fields of marketing and economics shed light on important issues regarding consumers’ participation in setting prices, the use and abuse of online ratings, the processing of price and coupon information, and the economics of online price dispersion. Next, we elucidate these four issues and highlight the contributions of the nine articles comprising this special issue.
Neuropilin‐1 is required for endothelial tip cell guidance in the developing central nervous system
Authors: Gerhardt Holger , Ruhrberg Christiana , Abramsson Alexandra , Fujisawa Hajime , Shima David , Betsholtz Christer
Published: September 2004

Recent evidence indicates that sprouting angiogenesis in the central nervous system (CNS) is a guided process similar to the guidance of axons and insect tracheal tubes. Specialized tip cells of vessel sprouts navigate in response to local depots or gradients of vascular endothelial growth factor (VEGF‐A). Neuropilin‐1 (Nrp‐1) is a transmembrane receptor with a repulsive function in axon guidance. Nrp‐1 also binds the VEGF‐A splice isoform VEGF165, stimulates angiogenesis, and is necessary for vascular development in the mouse. However, the morphogenetic events controlled by Nrp‐1 in angiogenesis have not been defined. Here, we analyzed endothelial tip cell guidance in the CNS of Nrp‐1–deficient mice. We focused our attention on the developing hindbrain, which is normally vascularized in a stereotyped manner. Initially, angiogenic sprouts extend along radial glia from the pial surface toward the ventricles, but in the subventricular zone (SVZ), they leave the radial path, turn laterally, and fuse to form a capillary plexus. Radial sprout elongation correlated with tip cell filopodia extensions along nestin‐positive radial glial processes, but in the SVZ, the tip cell filopodia also extended perpendicular to the glial tracks and made contact with filopodia of the neighboring sprouts. In Nrp‐1–deficient mice, the tip cell filopodia remained associated with the radial glia in the SVZ, which correlated with a failure of sprout turning and elongation across this region. As a result, the sprouts remained blind‐ended forming glomeruloid tufts in the SVZ. These observations suggest that Nrp‐1 plays an important role in allowing the endothelial tip cell filopodia to switch substrate and protrude in a new direction at a specific location in the developing brain. Developmental Dynamics 231:503–509, 2004. © 2004 Wiley‐Liss, Inc.
Analysis of the Tcf‐3 promoter during early development of Xenopus
Authors: Spieker Nicole , Peterson Josi , Reneman Stefan , Destrée Olivier
Published: September 2004

XTcf‐3 functions as a transcriptional regulator in the canonical Wnt signaling cascade and can repress or activate downstream target genes. Expression of XTcf‐3 is differentially regulated in time and place during development (Molenaar et al. [1998] Mech Dev. 75:151–154), but little is known about the mechanisms that control transcriptional activation and repression. A 15‐kb genomic fragment of Tcf‐3 sequences from Xenopus tropicalis was cloned, including the 5′ untranslated region; exons 1, 2, and 3; and intron sequences. We used 5′ deletion constructs for transgenesis and episomal luciferase assays in Xenopus to examine temporal and spatial regulation of the promoter during early development. A −3054/+34‐bp Tcf‐3 upstream region was identified that drives a green fluorescent protein (GFP) reporter transgene in a pattern similar to endogenous expression of XtTcf‐3 from gastrula to tail bud stages. At stage 12, expression of the reporter is restricted to the middle and posterior neurectoderm. At stage 22, expression is strongest in the neural plate, the eye anlagen and branchial arches. At stage 35/36, expression is found in the head mesenchyme, the branchial arches, the heart, the mesencephalon, eyes, otic vesicles, notochord, somites and the lateral plate mesoderm. Part of the cis‐acting elements driving this GFP reporter transgene expression map between −372 and −95 bp of the transcription start site. Furthermore, two TCF/LEF sites are necessary for full activity of the promoter during gastrula stages in episomal luciferase assays. Developmental Dynamics 231:510–517, 2004. © 2004 Wiley‐Liss, Inc.
Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons
Authors: Colombo Elena , Galli Rossella , Cossu Giulio , Gécz Jozef , Broccoli Vania
Published: September 2004

Mutations in the human ARX gene show unusually heterogeneous clinical presentations, including syndromic and nonsyndromic mental retardation, myoclonic epilepsy with spasticity, and lissencephaly with abnormal genitalia, that are believed to arise from an impairment of the embryonic mechanisms building the anterior central nervous system structures. Here, we show that the murine ortholog Arx has a highly dynamic expression pattern during both early shaping of the forebrain vesicle and later major events of neural migrations and cell‐type specification. Early on, the Arx gene is specifically activated in anterior forebrain anlage. Afterward, Arx expression is confined to the telencephalic vesicles and is enhanced during differentiation of the subpallial structures of the ganglionic eminences, overlapping with Dlx2, Dlx5, and Gad1 transcriptional domains. Tangentially migrating neurons reaching the cortical plate are also Arx‐positive at all embryonic stages analyzed. RNA–protein colabeling staining shows that Arx expression is maintained in the mature cortical interneurons, suggesting its involvement in the different functions of the γ‐aminobutyric acid (GABA)ergic neurons settled into the adult cerebral cortex. Finally, Arx expression is detected in the anterior subventricular layer of the adult brain, where neural stem cells have been shown to be located. Of interest, Arx expression is highly up‐regulated during in vitro differentiation of pure neural stem cell cultures retrieved from adult brain. All together, these findings suggest Arx as a gene involved in the commitment of proliferating neuroblasts into a GABAergic neuronal fate. In conclusion, our mouse Arx expression data provide important further insights into the puzzling complexity of the human ARX mutation pleiotropy. Developmental Dynamics 231:631–639, 2004. © 2004 Wiley‐Liss, Inc.
Histone deacetylase 1 (HDAC‐1) required for the normal formation of craniofacial cartilage and pectoral fins of the zebrafish
Authors: Pillai Renjitha , Coverdale Louise E. , Dubey Gaytri , Martin C. Cristofre
Published: September 2004

Histone deacetylases interact with nucleosomes to facilitate the formation of transcriptionally repressed chromatin. In the present study, we show that histone deacetylase 1 (hdac‐1) is expressed throughout embryonic development of the zebrafish. The expression of hdac‐1 is ubiquitous in early embryos (2–16 hr postfertilization), but at later stages (36 and 48 hr postfertilization), it is primarily restricted to the branchial arches, fin bud mesenchyme, and hindbrain. We report the phenotypes of hdac‐1 homozygous mutant embryos and embryos injected with an hdac‐1 antisense morpholino. These embryos possess a complex phenotype affecting several embryonic structures. We observed developmental abnormalities in the heart and neural epithelial structures, including the retina and the loss of craniofacial cartilage and pectoral fins. Developmental Dynamics 231:647–654, 2004. © 2004 Wiley‐Liss, Inc.
Analysis of Mlc‐lacZ Met mutants highlights the essential function of Met for migratory precursors of hypaxial muscles and reveals a role for Met in the development of hyoid arch‐derived facial muscles
Authors: Prunotto Chiara , Crepaldi Tiziana , Forni Paolo E. , Ieraci Alessandro , Kelly Robert G. , Tajbakhsh Shahragim , Buckingham Margaret , Ponzetto Carola
Published: September 2004

The Pax3 and c‐met genes are necessary for the development of tongue, diaphragm, and limb muscles. These hypaxial muscles derive from precursors that migrate out of the ventrolateral lip of the somites at occipital, cervical, and limb levels. In this work, we re‐examined primary myogenesis in c‐met signaling mutants using a skeletal muscle‐specific lacZ transgene (Mlc3f‐nlacZ‐2E). This strategy allowed us to identify precisely the shoulder, limb, tongue, and dermal muscles that need Met for development and to confirm that the morphological structure of epaxial and body wall muscles was normal, even in the most severe c‐met mutant. Surprisingly, however, X‐gal staining showed that, in this mutant, hyoid arch‐derived facial muscles were either reduced or absent, thus revealing that Met also contributes to the development of muscles in the head. Developmental Dynamics 231:582–591, 2004. © 2004 Wiley‐Liss, Inc.
Development of the lymphatic vascular system: A mystery unravels
Authors: Hong Young‐Kwon , Shin Jay W. , Detmar Michael
Published: September 2004

The blood vascular and the lymphatic system play complementary roles in tissue perfusion and fluid reabsorption. Despite its critical role in mediating tissue fluid homeostasis, intestinal lipid absorption, and the immune response, the lymphatic system has not received as much attention as the blood vascular system, largely due to a lack of lymphatic‐specific markers and to the dearth of knowledge about the molecular regulation of lymphatic development and function. A series of recent landmark studies now significantly has advanced our understanding of the lymphatic system. Based upon the discovery and characterization of lymphatic‐specific growth factors, receptors, and transcriptional regulators, the mystery of lymphatic vascular system development begins to be unraveled. The successful isolation and cultivation of blood vascular and lymphatic endothelial cells has enabled comparative molecular and cellular analyses of these two genetically and developmentally closely related cell lineages. Moreover, studies of several genetic mouse models have set the framework for a new molecular model of embryonic lymphatic vascular development and have identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Although these rapid advances already have led to development of the first lymphatic‐targeted molecular therapies, there still remain many unanswered questions regarding almost every aspect of lymphatic vascular biology, making the lymphatic system a highly exciting and rewarding field of study. Developmental Dynamics 231:462–473, 2004. © 2004 Wiley‐Liss, Inc.
Microfabricated fractal branching networks
Authors: Vozzi G. , Previti A. , Ciaravella G. , Ahluwalia A.
Published: September 2004

In this article, we demonstrate how a combination of engineering and biological techniques could lead to the realization of branched microstructures that can be used for the repair of damaged vascularized tissue. Recursive “treelike” networks were first generated by using fractal algorithms based on Murray's equation for vascular branching as well as allometric scaling rules. Two‐ and three‐dimensional branching patterns with different levels of complexity were then microfabricated from poly‐lactide‐co‐glycolide (PLGA) by using the pressure‐assisted microsyringe (PAM) system developed in our laboratory. Human endothelial cells isolated from umbilical cords were seeded on the microfabricated branched scaffolds to evaluate their effectiveness in supporting site‐specific cell adhesion. The results show that cell densities on the networks increase with complexity up to the sixth level and are then constant independent of branching level. The implications of this finding are discussed in terms of contact inhibition of “capillaries.” © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 326–333, 2004
Comparison of hydroxyapatite and beta tricalcium phosphate as bone substitutes after excision of bone tumors
Authors: Ogose Akira , Hotta Tetsuo , Kawashima Hiroyuki , Kondo Naoki , Gu Wenguang , Kamura Takeshi , Endo Naoto
Published: September 2004

Long‐term results are reported in 23 patients and short‐term results in 30 patients presenting with bone tumors treated by curettage or resection followed by implantation of hydroxyapatite (HA) or highly purified beta‐tricalcium phosphate (β‐TCP), respectively. Mean follow‐up was 97 and 26 months in cases involving HA implantation and β‐TCP implantation, respectively. Radiographs revealed HA incorporation into host bone in all but two cases; moreover, no obvious evidence of HA biodegradation was observed. A single patient exhibited late deformity following implantation of HA. All grafted β‐TCP was, at least partially, absorbed and replaced by newly formed bone. The mean period required for the disappearance of radiolucent zones between the ceramics and host bone was 17 weeks in HA and 9.7 weeks in β‐TCP. Highly purified β‐TCP appears to be advantageous relative to HA for surgical intervention in bone tumors consequent to the nature of remodeling and superior osteoconductivity. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 94–101, 2005