bluuebunny/crossref_metadata_2025 huggingface dataset:
Recessively inherited coagulation disorders
Authors: Mannucci Pier Mannuccio , Duga Stefano , Peyvandi Flora
Published: May 2004

Deficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500 000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. We investigated more than 1000 patients with recessively inherited coagulation disorders from Italy and Iran, a country with a high rate of recessive diseases due to the custom of consanguineous marriages. Based upon this experience, this article reviews the genetic basis, prevalent clinical manifestations, and management of these disorders. The steps and actions necessary to improve the condition of these often neglected patients are outlined.
Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial
Authors: Lee Stephanie J. , Zahrieh David , Agura Edward , MacMillan Margaret L. , Maziarz Richard T. , McCarthy Philip L. , Ho Vincent T. , Cutler Corey , Alyea Edwin P. , Antin Joseph H. , Soiffer Robert J.
Published: May 2004

The standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted. A total of 102 evaluable subjects of the targeted 166 were enrolled at 5 participating sites. Methylprednisolone at a dose of 2 mg/kg or daily equivalent was given in conjunction with daclizumab 1 mg/kg or placebo on study days 1, 4, 8, and weekly as long as clinically indicated. The groups were balanced for clinical characteristics. GVHD response rates by study day 42 were similar (53% vs 51%; P = .85). The study was halted after a planned interim analysis showed a significantly worse 100-day survival in the group receiving corticosteroids plus daclizumab (77% vs 94%; P = .02). Overall survival at 1 year was also inferior in the combination arm (29% vs 60%; P = .002). Both relapse- and GVHD-related mortality contributed to the increased mortality in the combination group. The combination of corticosteroids and daclizumab should not be used as initial therapy of acute GVHD.
Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs
Authors: Hubloue Ives , Rondelet Benoît , Kerbaul François , Biarent Dominique , Milani Guiti Malekzadeh , Staroukine Michel , Bergmann Pierre , Naeije Robert , Leeman Marc
Published: May 2004

Introduction

The role played by several vasoactive mediators that are synthesized and released by the pulmonary vascular endothelium in the regulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear. As a potent vasoconstrictor, angiotensin II could be involved. We tested the hypothesis that angiotensin-converting enzyme inhibition by enalaprilat and type 1 angiotensin II receptor blockade by candesartan would inhibit HPV.

Methods

HPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa–Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin–angiotensin system was present.

Results

Administration of enalaprilat and candesartan did not affect the Ppa–Ppao gradient at baseline or during hypoxia. Plasma renin activity and angiotensin II immunoreactivity increased during hypoxia, and subsequent measurements were consistent with effective angiotensin-converting enzyme inhibition after administration of enalaprilat, and with angiotensin receptor blockade after administration of candesartan.

Conclusion

These results suggest that, although the renin–angiotensin system was activated in hypoxia, angiotensin II is not normally involved in mediating acute HPV.
The Effects of Estrogen on the Expression of Genes Underlying the Differentiation of Somatic Cells in the Murine Gonad
Authors: Britt Kara L. , Stanton Peter G. , Misso Marie , Simpson Evan R. , Findlay Jock K.
Published: May 2004

Estrogen (17β-estradiol, E2)-deficient aromatase knockout (ArKO) mice develop Sertoli and Leydig cells at puberty. We hypothesized that estrogen, directly or indirectly, regulates genes responsible for somatic cell differentiation and steroidogenesis. ArKO ovaries expressed estrogen receptors α and β, and LH receptor, indices of estrogen responsiveness in the ovary. Wild-type (Wt) and ArKO mice received either E2 or placebo for 3 wk, from 7–10 wk of age. E2 decreased serum FSH and LH and increased uterine weights of 10-wk-old ArKO mice. We measured mRNA expression of Sertoli cell, Sry-like HMG box protein 9 (Sox9); three upstream transcription factors, liver receptor homolog-1 (Lrh-1), steroidogenic factor 1, and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1; and one downstream factor, Müllerian-inhibiting substance. Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17α-hydroxylase, 17β-hydroxysteroid dehydrogenase type-3, and 17β-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. In conclusion, the expression of the genes regulating somatic cell differentiation is directly or indirectly responsive to estrogen.
Region-Specific Reduction in Leptin-Induced Phosphorylation of Signal Transducer and Activator of Transcription-3 (STAT3) in the Rat Hypothalamus Is Associated with Leptin Resistance during Pregnancy
Authors: Ladyman S. R. , Grattan D. R.
Published: May 2004

Leptin concentrations increase during pregnancy, but this does not prevent the pregnancy-induced increase in food intake, suggesting a state of leptin resistance. This study investigated the response to intracerebroventricular leptin administration in pregnant rats. After fasting, nonpregnant, d-7 and d-14 pregnant rats received leptin (4 μg) or vehicle, then food intake was measured. Serial blood samples were collected in another group of rats to determine plasma leptin concentrations. Further groups of d-14 pregnant and nonpregnant rats were killed after leptin or vehicle treatment, and brains were collected. Hypothalamic nuclei were microdissected, and levels of signal transducer and activator of transcription (STAT)3 phosphorylation were measured using Western blot analysis. Fasting decreased leptin concentrations in both pregnant and nonpregnant rats. Leptin treatment significantly reduced food intake in nonpregnant and d-7 pregnant rats but not in d-14 pregnant rats. In addition, there was no postfasting hyperphagic response in the pregnant rats. In the pregnant rats, leptin-induced STAT3 phosphorylation was suppressed in the arcuate nucleus and, to a lesser extent, in the ventromedial hypothalamus (VMH), compared with nonpregnant rats. Unstimulated STAT3 levels were also decreased in the VMH during pregnancy. Leptin-induced phosphorylation of STAT3 in the dorsomedial and lateral hypothalamus was not different between pregnant and nonpregnant rats. These data indicate that pregnant rats become resistant to the satiety action of leptin. Furthermore, leptin-induced activation of the STAT3 is impaired during pregnancy, specifically in the arcuate nucleus and VMH. These data support the hypothesis that pregnancy is a state of hypothalamic leptin resistance.
The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice
Authors: Kelly Olivia G. , Pinson Kathy I. , Skarnes William C.
Published: May 2004

Recent work has identified LDL receptor-related family members, Lrp5 and Lrp6, as co-receptors for the transduction of Wnt signals. Our analysis of mice carrying mutations in both Lrp5 and Lrp6 demonstrates that the functions of these genes are redundant and are essential for gastrulation. Lrp5;Lrp6 double homozygous mutants fail to establish a primitive streak, although the anterior visceral endoderm and anterior epiblast fates are specified. Thus, Lrp5 and Lrp6 are required for posterior patterning of the epiblast, consistent with a role in transducing Wnt signals in the early embryo. Interestingly, Lrp5+/-;Lrp6-/- embryos die shortly after gastrulation and exhibit an accumulation of cells at the primitive streak and a selective loss of paraxial mesoderm. A similar phenotype is observed in Fgf8 and Fgfr1 mutant embryos and provides genetic evidence in support of a molecular link between the Fgf and Wnt signaling pathways in patterning nascent mesoderm. Lrp5+/-;Lrp6-/- embryos also display an expansion of anterior primitive streak derivatives and anterior neurectoderm that correlates with increased Nodal expression in these embryos. The effect of reducing, but not eliminating, Wnt signaling in Lrp5+/-;Lrp6-/- mutant embryos provides important insight into the interplay between Wnt, Fgf and Nodal signals in patterning the early mouse embryo.
A role for MKP3 in axial patterning of the zebrafish embryo
Authors: Tsang Michael , Maegawa Shingo , Kiang Anne , Habas Raymond , Weinberg Eric , Dawid Igor B.
Published: May 2004

Fibroblast growth factors (FGFs) are secreted molecules that can activate the RAS/mitogen-activated protein kinase (MAPK) pathway to serve crucial functions during embryogenesis. Through an in situ hybridization screen for genes with restricted expression patterns during early zebrafish development,we identified a group of genes that exhibit similar expression patterns to FGF genes. We report the characterization of zebrafish MAP kinase phosphatase 3(MKP3; DUSP6 - Zebrafish Information Network), a member of the FGF synexpression group, showing that it has a crucial role in the specification of axial polarity in the early zebrafish embryo. MKP3 dephosphorylates the activated form of MAPK, inhibiting the RAS/MAPK arm of the FGF signaling pathway. Gain- and loss-of-function studies reveal that MKP3 is required to limit the extent of FGF/RAS/MAPK signaling in the early embryo, and that disturbing this inhibitory pathway disrupts dorsoventral patterning at the onset of gastrulation. The earliest mkp3 expression is restricted to the future dorsal region of the embryo where it is initiated by a maternalβ-catenin signal, but soon after its initiation, mkp3 expression comes under the control of FGF signaling. Thus, mkp3 encodes a feedback attenuator of the FGF pathway, the expression of which is initiated at an early stage so as to ensure correct FGF signaling levels at the time of axial patterning.
An interactive network of zinc-finger proteins contributes to regionalization of the Drosophila embryo and establishes the domains of HOM-C protein function
Authors: Robertson Lisa K. , Bowling Dana B. , Mahaffey James P. , Imiolczyk Barbara , Mahaffey James W.
Published: May 2004

During animal development, the HOM-C/HOX proteins direct axial patterning by regulating region-specific expression of downstream target genes. Though much is known about these pathways, significant questions remain regarding the mechanisms of specific target gene recognition and regulation, and the role of co-factors. From our studies of the gnathal and trunk-specification proteins Disconnected (DISCO) and Teashirt (TSH), respectively, we present evidence for a network of zinc-finger transcription factors that regionalize the Drosophila embryo. Not only do these proteins establish specific regions within the embryo, but their distribution also establishes where specific HOM-C proteins can function. In this manner, these factors function in parallel to the HOM-C proteins during axial specification. We also show that in tsh mutants, disco is expressed in the trunk segments, probably explaining the partial trunk to head transformation reported in these mutants, but more importantly demonstrating interactions between members of this regionalization network. We conclude that a combination of regionalizing factors, in concert with the HOM-C proteins,promotes the specification of individual segment identity.
The Wnt/β-catenin pathway directs neuronal differentiation of cortical neural precursor cells
Authors: Hirabayashi Yusuke , Itoh Yasuhiro , Tabata Hidenori , Nakajima Kazunori , Akiyama Tetsu , Masuyama Norihisa , Gotoh Yukiko
Published: May 2004

Neural precursor cells (NPCs) have the ability to self-renew and to give rise to neuronal and glial lineages. The fate decision of NPCs between proliferation and differentiation determines the number of differentiated cells and the size of each region of the brain. However, the signals that regulate the timing of neuronal differentiation remain unclear. Here, we show that Wnt signaling inhibits the self-renewal capacity of mouse cortical NPCs,and instructively promotes their neuronal differentiation. Overexpression of Wnt7a or of a stabilized form of β-catenin in mouse cortical NPC cultures induced neuronal differentiation even in the presence of Fgf2, a self-renewal-promoting factor in this system. Moreover, blockade of Wnt signaling led to inhibition of neuronal differentiation of cortical NPCs in vitro and in the developing mouse neocortex. Furthermore, theβ-catenin/TCF complex appears to directly regulate the promoter of neurogenin 1, a gene implicated in cortical neuronal differentiation. Importantly, stabilized β-catenin did not induce neuronal differentiation of cortical NPCs at earlier developmental stages, consistent with previous reports indicating self-renewal-promoting functions of Wnts in early NPCs. These findings may reveal broader and stage-specific physiological roles of Wnt signaling during neural development.
Rab7 is required for the normal progression of the autophagic pathway in mammalian cells
Authors: Gutierrez Maximiliano G. , Munafó Daniela B. , Berón Walter , Colombo María I.
Published: May 2004

Autophagy is a normal degradative pathway that involves the sequestration of cytoplasmic components and organelles in a vacuole called an autophagosome that finally fuses with the lysosome. Rab7 is a member of the Rab family involved in transport to late endosomes and in the biogenesis of the perinuclear lysosome compartment. To assess the role of Rab7 in autophagy we stably transfected CHO cells with wild-type pEGFP-Rab7, and the mutants T22N (GDP form) and Q67L (GTP form). Autophagy was induced by amino acid starvation and the autophagic vacuoles were labeled with monodansylcadaverine. By fluorescence microscopy we observed that Rab7wt and the active mutant Rab7Q67L were associated with ring-shaped vesicles labeled with monodansylcadaverine indicating that these Rab proteins associate with the membrane of autophagic vesicles. As expected, in cells transfected with the negative mutant Rab7T22N the protein was diffusely distributed in the cytosol. However, upon induction of autophagy by amino acid starvation or by rapamycin treatment this mutant clearly decorated the monodansylcadaverine-labeled vesicles. Furthermore, a marked increase in the size of the monodansylcadaverine-labeled vacuoles induced by starvation was observed by overexpression of the inactive mutant T22N. Similarly, there was an increase in the size of vesicles labeled with LC3, a protein that specifically localizes on the autophagosomal membrane. Taken together the results indicate that a functional Rab7 is important for the normal progression of autophagy.
Selective assembly of connexin37 into heterocellular gap junctions at the oocyte/granulosa cell interface
Authors: Veitch Gregory I. , Gittens Joanne E. I. , Shao Qing , Laird Dale W. , Kidder Gerald M.
Published: May 2004

Studies of mice with targeted disruptions of specific connexin genes have revealed that at least two connexins, connexin37 (Cx37) and connexin43 (Cx43), play essential roles in ovarian follicle development. To explore the respective roles of these two connexins in gap-junctional communication between the developing murine oocyte and its surrounding cumulus granulosa cells, we used confocal immunofluorescence microscopy and oocyte preloading functional assays. Immunofluorescence microscopy located Cx37 within gap-junction plaques between granulosa cells and the oocyte, and Cx43 between surrounding granulosa cells. Preloading assays combining denuded oocytes and cultured granulosa cells expressing or lacking Cx37 or Cx43 revealed that Cx37 must be present in both cell types for the establishment of heterocellular gap-junctional coupling. Furthermore, immunofluorescence microscopy of cultured granulosa cells after incubation with denuded oocytes showed that the oocyte induces the formation of gap junctions containing Cx37 at the surface of granulosa cells. Continuous Cx37 expression in granulosa cells was confirmed using RT-PCR. Together, these results indicate that the growing murine oocyte is functionally coupled with granulosa cells by homotypic gap junctions composed of Cx37, and that the formation and/or stabilization of Cx37 junctions is selectively induced at the oocyte-granulosa interface by cell contact.
Effective Heuristics for Capacitated Production Planning with Multiperiod Production and Demand with Forecast Band Refinement
Authors: Kaminsky Philip , Swaminathan Jayashankar M.
Published: May 2004

In this paper we extend forecast band evolution and capacitated production modelling to the multiperiod demand case. In this model, forecasts of discrete demand for any period are modelled as bands and defined by lower and upper bounds on demand, such that future forecasts lie within the current band. We develop heuristics that utilize knowledge of demand forecast evolution to make production decisions in capacitated production planning environments. In our computational study we explore the efficiency of our heuristics, and also explore the impact of seasonality on demand and availability of information updates.
In this issue
Authors: van Ryzin Garrett J.
Published: May 2004

A regular feature of Manufacturing & Service Operation Management, “In this issue…” briefly describes each issue's articles and highlights their contributions.
FTY720 and Cyclosporine: Evaluation for a Pharmacokinetic Interaction
Authors: Kovarik John M , Schmouder Robert L , Barilla Denise , Büche Monika , Rouilly Marisel , Berthier Stephane , Wang Yibin , Van Saders Claudia , Mayer Thomas , Gottlieb Alice B
Published: May 2004

BACKGROUND:

FTY720 is a sphingosine-1-phosphate receptor agonist intended for use in immunoprophylaxis regimens to prevent acute rejection after organ transplantation.

OBJECTIVE:

To evaluate the potential for a pharmacokinetic drug interaction between the immunomodulator FTY720 and cyclosporine to support the use of this drug combination in organ transplantation.

METHODS:

In this open-label, randomized crossover study, 12 subjects with psoriasis received a single dose of FTY720 1 mg alone and on day 5 of an 8-day course of cyclosporine 200 mg twice daily. The single-dose pharmacokinetics of FTY720 and the steady-state pharmacokinetics of cyclosporine were characterized when given alone and during coadministration. Routine safety data were collected, with special attention to total blood lymphocyte counts and heart rate.

RESULTS:

Cyclosporine coadministration compared with FTY720 given alone did not significantly alter FTY720 maximum concentration (Cmax) (0.57 ± 0.17 vs 0.58 ± 0.19 • ng/mL, respectively) or AUC0-t (41 ± 13 vs 41 ± 13 ng • h/mL, respectively). Likewise for cyclosporine, FTY720 coadministration did not alter the steady-state Cmax compared with cyclosporine given alone (1452 ± 308 vs 1376 ± 149 ng/mL, respectively) or AUCτ (6385 ± 1578 vs 6031 ± 1051 ng • h/mL, respectively). Mean lymphocyte counts decreased from baseline by an average of 35% over the first 2 days after FTY720 administration and thereafter increased to prestudy values by day 5 similarly in the absence and presence of cyclosporine. The morning mean supine heart rate decreased approximately 10% and returned to prestudy rates by day 5 after administration of FTY720 alone and with cyclosporine. Heart rate changes were asymptomatic in all study participants. One subject experienced asymptomatic second-degree type 1 atrioventricular (Wenckebach) block.

CONCLUSIONS:

The pharmacokinetics of single-dose FTY720 and steady-state cyclosporine were not altered during coadministration.
Natriuretic Peptides as Markers of Mild Forms of Left Ventricular Dysfunction: Effects of Assays on Diagnostic Performance of Markers
Authors: Hammerer-Lercher Angelika , Ludwig Wilma , Falkensammer Gerda , Müller Silvana , Neubauer Elke , Puschendorf Bernd , Pachinger Otmar , Mair Johannes
Published: May 2004

Background: We compared the performance of different natriuretic peptides to diagnose mild forms of left ventricular dysfunction (LVD) and investigated the influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays on the diagnostic performance of these markers.

Methods: We measured BNP (Triage® BNP), NT-proBNP (Biomedica), and N-terminal pro-A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients (age range, 28–83 years) with clinically suspected mild LVD. In patients with sufficient sample volume, we measured BNP and NT-proBNP with additional assays (Shionoria and Roche, respectively).

Results: For identifying patients with mild systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence interval) areas under the curves (AUC) of 0.78 (0.63–0.89) and 0.75 (0.58–0.87), respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48–0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed equally well for the diagnosis of systolic LVD despite the poor agreement between NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic performance of the Triage BNP [AUC, 0.70 (0.56–0.81)] was significantly better (P = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34–0.65)]. Furthermore, the performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03) than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD.

Conclusions: The performance of BNP for the diagnosis of systolic or diastolic LVD is not affected by the assay used, whereas the performance of NT-proBNP for the diagnosis of isolated diastolic LVD is assay dependent.
ROC Curves in Clinical Chemistry: Uses, Misuses, and Possible Solutions
Authors: Obuchowski Nancy A , Lieber Michael L , Wians Frank H
Published: May 2004

Background: ROC curves have become the standard for describing and comparing the accuracy of diagnostic tests. Not surprisingly, ROC curves are used often by clinical chemists. Our aims were to observe how the accuracy of clinical laboratory diagnostic tests is assessed, compared, and reported in the literature; to identify common problems with the use of ROC curves; and to offer some possible solutions.

Methods: We reviewed every original work using ROC curves and published in Clinical Chemistry in 2001 or 2002. For each article we recorded phase of the research, prospective or retrospective design, sample size, presence/absence of confidence intervals (CIs), nature of the statistical analysis, and major analysis problems.

Results: Of 58 articles, 31% were phase I (exploratory), 50% were phase II (challenge), and 19% were phase III (advanced) studies. The studies increased in sample size from phase I to III and showed a progression in the use of prospective designs. Most phase I studies were powered to assess diagnostic tests with ROC areas ≥0.70. Thirty-eight percent of studies failed to include CIs for diagnostic test accuracy or the CIs were constructed inappropriately. Thirty-three percent of studies provided insufficient analysis for comparing diagnostic tests. Other problems included dichotomization of the gold standard scale and inappropriate analysis of the equivalence of two diagnostic tests.

Conclusion: We identify available software and make some suggestions for sample size determination, testing for equivalence in diagnostic accuracy, and alternatives to a dichotomous classification of a continuous-scale gold standard. More methodologic research is needed in areas specific to clinical chemistry.
HyperScout: Linkvorschau im World Wide Web (HyperScout: Link Preview for the World Wide Web)
Authors: Weinreich Harald , Obendorf Hartmut , Lamersdorf Winfried
Published: May 2004

Die Benutzung eines Web-Browsers ist einfach zu erlernen, dennoch stellt die Navigation im Web selbst für erfahrene Benutzer immer wieder Herausforderungen bereit. Einer der Gründe dafür liegt in der Vielfalt von Linkarten und Linkzielen, die für den Benutzer oft nicht transparent sind und ihn so vor Überraschungen stellen, nachdem er einen Link angeklickt hat. Das Projekt HyperScout beschäftigt sich mit Möglichkeiten, die Navigation im Web zu vereinfachen, indem man Informationen zum Typ des Links und zum referenzierten Objekt für den Benutzer sichtbar macht. Dieser Bericht stellt die entwickelten Konzepte und die Ergebnisse einer Evaluation des daraus abgeleiteten Prototyps vor. Die Ergebnisse geben Aufschlüsse darüber, welche Informationen Benutzern vor der Anwahl eines Links hilfreich sind und wie sie dargestellt werden könnten.
THE ASIA-EUROPE MEETING AND INTER-REGIONALISM: Toward a Theory of Multilateral Utility
Authors: Dent Christopher M.
Published: May 2004

The Asia-Europe Meeting framework was created in 1996, its primary purpose being to fortify relations between the East Asian region and the European Union. Moreover, ASEM partners must not only concern themselves with developing closer interregional ties but also attend to the significant global impact of their partnership, and thus the responsibilities that lie therein.
LEADERSHIP TRANSITION, INTRA-PARTY DEMOCRACY, AND INSTITUTION BUILDING IN CHINA
Authors: Lin Gang
Published: May 2004

Recent leadership transition in China was a mixture of institutional formalization and political personalization. Intra-party democracy has been conducted within the framework of one-party rule and guided by the predetermined principle of democratic centralism. Past choices of rules constrain China's institution building, while providing new opportunities for the reform elite.
Extracting Light from Polymer Light‐Emitting Diodes Using Stamped Bragg Gratings
Authors: Ziebarth J. M. , Saafir A. K. , Fan S. , McGehee M. D.
Published: May 2004

In this paper, we describe a method for increasing the external efficiency of polymer light‐emitting diodes (LEDs) by coupling out waveguided light with Bragg gratings. We numerically model the waveguide modes in a typical LED structure and demonstrate how optimizing layer thicknesses and reducing waveguide absorption can enhance the grating outcoupling. The gratings were created by a soft‐lithography technique that minimizes changes to the conventional LED structure. Using one‐dimensional and two‐dimensional gratings, we were able to increase the forward‐directed emission by 47 % and 70 %, respectively, and the external quantum efficiency by 15 % and 25 %.
Efficient Load Transfer to Polymer‐Grafted Multiwalled Carbon Nanotubes in Polymer Composites
Authors: Hwang G. L. , Shieh Y.‐T. , Hwang K. C.
Published: May 2004

Multiwalled carbon nanotubes (MWNTs) grafted with poly(methyl methacrylate) (PMMA) were synthesized by emulsion reactions and used as a reinforcement for commercial PMMA. Both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the applied tensile load on the composites was transferred to the PMMA‐grafted MWNTs, leading to a strain failure of the MWNTs rather than an adhesive failure between the MWNTs and the matrix. Dynamic mechanical analysis (DMA) data showed that the storage modulus at 20 °C of the PMMA composite containing 20 wt.‐% of the PMMA‐grafted MWNTs was significantly enhanced by ∼ 29 GPa (or by ∼ 1100 %) as compared with commercial PMMA.
Enhanced Photoelectrochemistry in CdS/Au Nanoparticle Bilayers
Authors: Sheeney‐Haj‐Ichia L. , Pogorelova S. , Gofer Y. , Willner I.
Published: May 2004

Three different configurations of Au‐nanoparticle/CdS‐nanoparticle arrays are organized on Au/quartz electrodes for enhanced photocurrent generation. In one configuration, Au‐nanoparticles are covalently linked to the electrode and the CdS‐nanoparticles are covalently linked to the bare Au‐nanoparticle assembly. The resulting photocurrent, φ = 7.5 %, is ca. 9‐fold higher than the photocurrent originating from a CdS‐nanoparticle layer that lacks the Au‐nanoparticles, φ = 0.8 %. The enhanced photocurrent in the Au/CdS nanoparticle array is attributed to effective charge separation of the electron–hole pair by the injection of conduction‐band electrons from the CdS‐ to the Au‐nanoparticles. Two other configurations involving electrostatically stabilized bipyridinium‐crosslinked Au/CdS or CdS/Au nanoparticle arrays were assembled on the Au/quartz crystal. The photocurrent quantum yields in the two systems are φ = 10 % and φ = 5 %, respectively. The photocurrents in control systems that include electrostatically bridged Au/CdS or CdS/Au nanoparticles by oligocationic units that lack electron‐acceptor units are substantially lower than the values observed in the analogous bipyridinium‐bridged systems. The enhanced photocurrents in the bipyridinium‐crosslinked systems is attributed to the stepwise electron transfer of conduction‐band electrons to the Au‐nanoparticles by the bipyridinium relay bridge, a process that stabilizes the electron–hole pair against recombination and leads to effective charge separation.
The Influence of the Phase Morphology on the Optoelectronic Properties of Light‐Emitting Electrochemical Cells
Authors: Wenzl F. P. , Pachler P. , Suess C. , Haase A. , List E. J. W. , Poelt P. , Somitsch D. , Knoll P. , Scherf U. , Leising G.
Published: May 2004

We report on the morphological aspects of thin films prepared from a blue–green light‐emitting conjugated polymer, (methyl‐substituted ladder‐type poly(p‐phenylene, mLPPP)), blended with a solid‐state electrolyte composed either by a crown ether, dicyclohexano‐18‐crown‐6 (DCH18C6), or a high‐molecular‐weight poly(ethylene oxide) (HMWPEO), and a Li salt, lithium trifluoromethanesulfonate (LiCF3SO3, Li triflate (LiTf)), as they have been successfully applied in light‐emitting electrochemical cells (LECs). The surface morphologies of the blend layers were investigated using atomic force microscopy (AFM) in tapping mode, and the ion distribution was probed using X‐ray analysis by means of energy‐dispersive X‐ray spectrometry (EDXS) in the scanning electron microscope (SEM). We show that the two different phase‐separation processes, the complexation tendencies of the ionic species as well as the ionic transport numbers, have tremendous influence on the performances of the corresponding LECs, revealing either rectifying or symmetric optoelectronic characteristics in forward and reverse bias directions. This opens up new possibilities for tuning the optoelectronic properties of ion‐supported organic electronic devices.
Alkyl Substituent Effects on the Conductivity of Polyaniline
Authors: Zaidi N. A. , Foreman J. P. , Tzamalis G. , Monkman S. C. , Monkman A. P.
Published: May 2004

The oxidative polymerization of aniline hydrochloride derivatives in water at low temperature is studied without lithium chloride. The resulting polymers have high molecular weight but the conductivity of the acid‐doped films is strongly dependent on the alkyl‐substituted chain at the 2‐positions. The root cause of the alkyl‐substitution effects is thoroughly investigated using density functional theory (DFT) methods (B3LYP using 6–1G(d,p) and 6‐311++G(2d,2p) basis sets). Internal structural changes observed on substitution appear to be more significant than a variety of electronic parameters measured using the natural bond orbital (NBO) method. Interplanar angles steadily increase on substitution, whereas ring orbital properties and the amount of ring delocalization remain fairly constant. An investigation into the extent to which lone pair–σ‐orbital overlap is affected by substitution indicates that increasing the steric bulk of the substituent reduces the ability of the lone pair to delocalize into the ring orbitals. However, the amount of overlap between the two is not adversely affected until the dihedral between them is > 30°, a situation that only occurs in i‐propyl and s‐butyl substitution. This finding is completely reflected in the experimental conductivity measurements.
Interface Engineering for Solid‐State Dye‐Sensitized Nanocrystalline Solar Cells: The Use of Ion‐Solvating Hole‐Transporting Polymers
Authors: Haque S. A. , Park T. , Xu C. , Koops S. , Schulte N. , Potter R. J. , Holmes A. B. , Durrant J. R.
Published: May 2004

The control of interfacial charge transfer is central to the design of photovoltaic devices. This charge transfer is strongly dependent upon the local chemical environment at each interface. In this paper we report a methodology for the fabrication of a novel nanostructured multicomponent film, employing a dual‐function supramolecular organic semiconductor to allow molecular‐level control of the local chemical composition at a nanostructured inorganic/organic semiconductor heterojunction. The multicomponent film comprises a lithium ion doped dual‐functional hole‐transporting material (Li+–DFHTM), sandwiched between a dye‐sensitized nanocrystalline TiO2 film and a mono‐functional organic hole‐transporting material (MFHTM). The DFHTM consists of a conjugated organic semiconductor with ion supporting side chains, designed to allow both electronic and ionic charge transport properties. The Li+–DFHTM layers provide a new and versatile way to control the interface electrostatics, and consequently the charge transfer, at a nanostructured dye‐sensitized inorganic/organic semiconductor heterojunction.
Estimation of copolymerization kinetic parameters by maximum likelihood method
Authors: Habibi Ali , Vasheghani‐Farahani Ebrahim
Published: May 2004

A kinetic study of free‐radical solution copolymerization of isobutyl methacrylate and lauryl methacrylate in benzene, initiated with 2,2‐azoisobutyronitrile (AIBN) was performed at different monomer feed compositions, at low conversion level. To avoid the complications of copolymerization kinetics, the compositional‐averaged rate constant method was applied to dead‐end polymerization in constant and variable volume polymerization systems. A conditional probability approach, with “maximum likelihood function” (MLF), was used for estimating the kinetic parameters from experimental data. This method provides point estimates as well as joint probability regions. The validity of this method was approved for the statistically justified and best estimation of the rate parameters in copolymerization systems. Statistical analysis indicated that, although copolymer composition is well described by the terminal unit model (TUM), the rate data are not. Like many other systems recently examined, the data were well represented by the implicit penultimate unit effect (IPUE) model of Fukuda and coworkers. It was found that the coupled rate parameter k̄p/k̄ is greater than the TUM predictions, whereas most of the previous systems studied have coupled rate parameters lower than those predicted by the TUM. An interactive computer simulator for parameter estimation was developed, which is run in two modes of estimation and prediction and is capable of receiving input data from both keyboard and databank. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1260–1272, 2004
Prediction of critical points: A new methodology using global optimization
Authors: Henderson Nélio , Freitas Léa , Platt Gustavo M.
Published: May 2004

In the present work we develop, implement, and analyze the results of a new methodology destined to calculate critical points of phase transitions. Our criticality conditions are developed from a slight modification of the Gibbs tangent plane criterion. We formulate the critical points calculation as an optimization problem. Such formulation offers many advantages, among them we can mention the capability of determining more than one critical point, the use of robust numerical methods, and the possibility of visualization of the critical phenomenon from a two‐variable (T and P) objective function. To solve the optimization problems we use the simulated annealing algorithm, a stochastic method whose convergence does not depend on initial guesses and gives preference to global optima. Several samples of mixtures were used to test the present methodology. The results of our simulations were compared, in a satisfactory way, with experimental data and with some results calculated in other approaches. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1300–1314, 2004
Is cascade testing a sensible method of screening a population for autosomal recessive disorders?
Authors: Morris J.K. , Law M.R. , Wald N.J.
Published: May 2004

Our aim was to evaluate “cascade testing” as a method of screening a population for autosomal recessive disorders. We used computer simulations to estimate screening performance according to carrier frequency, whether testing would extend to siblings, first or second cousins of identified carriers and family size. Cascade testing in populations with the distribution of family size current in England and Wales would require locating and testing a small proportion of the population as expected, but would detect few cases. For cystic fibrosis (carrier frequency of 4%), testing all siblings and first cousins of all identified carriers would require locating and testing only 1.9% of the whole population, but would detect only 15% of all new cases. Similarly for congenital adrenal hyperplasia (carrier frequency of 1%), testing all siblings and first cousins of all identified carriers would require locating and testing only 0.1% of the whole population, but would detect only 3.1% of all new cases. The detection rate increases with increasing carrier frequency, family size and extending the testing to second cousins of identified carriers, but at the cost of greater increases in the proportion of the population located and tested. The performance of cascade testing is too poor to justify its introduction into practice as a screening test for any autosomal recessive disorder. © 2004 Wiley‐Liss, Inc.
Early hearing detection and intervention programs: Opportunities for genetic services
Authors: White Karl R.
Published: May 2004

Congenital hearing loss is relatively frequent and has serious negative consequences if it is not diagnosed and treated during the first few months of life. Babies with hearing loss who are identified early and provided with appropriate intervention develop better language, cognitive, and social skills. As a result of improvements in screening equipment and procedures, newborn hearing screening programs have expanded rapidly in recent years, and almost 90% of all newborns are now screened for hearing loss before leaving the hospital. Because 50% or more of congenital hearing loss is due to genetic causes, providers of genetic services should play an increasingly important role in newborn hearing screening, diagnostic, and intervention services. For this to happen, parents, public health officials, and primary health care providers need to become better informed about the benefits of genetic services for children with hearing loss and their families. Providers of genetic services also need to become better informed about the current status of Early Hearing Detection and Intervention (EHDI) programs and how they can contribute to continued improvement of these programs. © 2004 Wiley‐Liss, Inc.
Interstitial deletion of chromosome 2q32‐34 associated with multiple congenital anomalies and a urea cycle defect (CPS I deficiency)
Authors: Loscalzo M.L. , Galczynski R.L. , Hamosh A. , Summar M. , Chinsky J.M. , Thomas G.H.
Published: May 2004

A de novo deletion of the long arm of chromosome 2 at 2q31‐33 was observed in the fetal amniocyte G‐banded karyotype performed because of possible multiple malformations identified by ultrasound at 23 weeks gestation. Two days after the uneventful term delivery of a 2.45 kg male, the neonate experienced cardiopulmonary decompensation and biochemical changes compatible with carbamoyl phosphate synthetase I (CPS I) deficiency (elevated ammonia with a peak of 948 μmol/L, deficiency of citrulline, and no increase in orotic acid). The child died on day 3 of life. Physical anomalies confirmed at autopsy included double superior vena cava, ectopic adrenal tissue, and metatarsus adductus. The autopsy also revealed histologic evidence consistent with CPS deficiency, most notably microvesicular steatosis of the liver and Alzheimers Type II changes with hypertrophic astrocytes in the basal ganglia. A postnatal lymphocyte karyotype confirmed the chromosome 2q31‐33 deletion. Enzyme analysis on postmortem liver tissue confirmed the diagnosis of CPS deficiency.CPS Iis reported to be mapped to 2q35 by NCBI (http://www.ncbi.nlm.nih.gov/mapview/) and 2q34 by ENSEMBL (http://www.ensembl.org/). The UCSC Human Genome Browser July 2003 assembly also places the gene at 2q34 (http://genome.UCSC.edu/). Fluorescence in situ hybridization (FISH) analysis with a BAC clone (RP11‐349G4) ofCPS Idemonstrated that one copy of the gene was deleted in this infant. Using additional probes corresponding to the bands in the region of deletion, we identified the deleted region as 2q32‐2q34. Our observations support theCPS Imap position (ENSEMBL, UCSC) at 2q34. Additionally, potential conditions associated with deletions narrowly defined by standard cytogenetic techniques merit consideration in prenatal counseling. As demonstrated here, deletions may not only result in malformations and mental retardation but also increase the likelihood of revealing mutated genes located in the undeleted region of the homologous chromosome. © 2004 Wiley‐Liss, Inc.
Osteopathia striata with cranial sclerosis: Clinical, radiological, and bone histological findings in an adolescent girl
Authors: Ward L.M. , Rauch F. , Travers R. , Roy M. , Montes J. , Chabot G. , Glorieux F.H.
Published: May 2004

Osteopathia striata with cranial sclerosis (OS–CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra‐skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French‐Canadian girl with a moderate to severe form of sporadic OS–CS. Multiple medical problems, including anal stenosis and the Pierre–Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis. © 2004 Wiley‐Liss, Inc.
Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children
Authors: Aléssio Ana Claudia M. , Annichino‐Bizzacchi Joyce M. , Bydlowski Sergio P. , Eberlin Marcos N. , Vellasco Adriana P. , Höehr Nelci Fenalti
Published: May 2004

Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms, folate, and B12 levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the MTHFR gene and A66G in the MTRR gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B12 levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B12 levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B12 levels demonstrated significant P‐values. The folate levels demonstrated a statistically significant decrease (P = 0.0477) from the C677T mutation in the MTHFR gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease. © 2004 Wiley‐Liss, Inc.
Mesomelic dysplasia, Kantaputra type: Clinical report, prenatal diagnosis, no evidence for SHOX deletion/mutation
Authors: Kwee M.L. , van de Sluijs J.A. , van Vugt J.M.G. , Wijnaendts L.C.D. , Gille J.J.P.
Published: May 2004

A grandmother, her three children, and three grandchildren had skeletal abnormalities consisting of a short stature, bilateral symmetrical very short, broad and bowed radii, very short and broad ulna, mildly short lower legs, short proximal end of fibula, abnormal ankles, abnormal calcaneus and talus and pes equinus. They had normal craniofacial features, normal intelligence and normal chromosomes. We concluded that this skeletal dysplasia resembles the autosomal dominant mesomelic dysplasia, Kantaputra type. Prenatal diagnosis by ultrasound examination early in the pregnancy was possible. We found no evidence for a SHOX gene deletion or point mutation. As far as we know this is the third reported family with this skeletal dysplasia. © 2004 Wiley‐Liss, Inc.