bluuebunny/crossref_metadata_2025 huggingface dataset:
Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
Authors: Hall Mary A. , Stroop Steven D. , Hu Mary C. , Walls Michael A. , Reddish Mark A. , Burt David S. , Lowell George H. , Dale James B.
Published: April 2004

We have previously shown that a hexavalent group A streptococcal M protein-based vaccine evoked bactericidal antibodies after intramuscular injection. In the present study, we show that the hexavalent vaccine formulated with several different mucosal adjuvants and delivered intranasally induced serum and salivary antibodies that protected mice from intranasal challenge infections with virulent group A streptococci. The hexavalent vaccine was formulated with liposomes with or without monophosphorylated lipid A (MPL), cholera toxin B subunit with or without holotoxin, or proteosomes fromNeisseria meningitidisouter membrane proteins complexed with lipopolysaccharide fromShigella flexneri. Intranasal immunization with the hexavalent vaccine mixed with these adjuvants resulted in significant levels of antibodies in serum 2 weeks after the final dose. Mean serum antibody titers were equivalent in all groups of mice except those that were immunized with hexavalent protein plus liposomes without MPL, which were significantly lower. Salivary antibodies were also detected in mice that received the vaccine formulated with the four strongest adjuvants. T-cell proliferative assays and cytokine assays using lymphocytes from cervical lymph nodes and spleens from mice immunized with the hexavalent vaccine formulated with proteosomes indicated the presence of hexavalent protein-specific T cells and a Th1-weighted mixed Th1-Th2 cytokine profile. Intranasal immunization with adjuvanted formulations of the hexavalent vaccine resulted in significant levels of protection (80 to 100%) following intranasal challenge infections with type 24 group A streptococci. Our results indicate that intranasal delivery of adjuvanted multivalent M protein vaccines induces protective antibody responses and may provide an alternative to parenteral vaccine formulations.
Evaluation of T-Cell Responses to Novel RD1- and RD2-EncodedMycobacterium tuberculosisGene Products for Specific Detection of Human Tuberculosis Infection
Authors: Liu Xiao-Qing , Dosanjh Davinder , Varia Hansa , Ewer Katie , Cockle Paul , Pasvol Geoffrey , Lalvani Ajit
Published: April 2004

The tuberculin skin test for diagnosingMycobacterium tuberculosisinfection suffers from antigenic cross-reactivity of purified protein derivative with BCG, resulting in poor specificity in BCG-vaccinated populations. Comparative genomics has identified several genetic regions inM. tuberculosisandM. bovisthat are deleted inM. bovisBCG. Proteins encoded in these regions will form the basis of new specific T-cell-based blood tests that do not cross-react with BCG, but only two, early secretory antigen target 6 and culture filtrate protein 10, have been studied in detail in humans. We investigated four novel gene products, encoded by RD2 (Rv1989c) and RD1 (Rv3873, Rv3878, and Rv3879c), that are absent from most or all of the vaccine strains of BCG, respectively. Sixty-seven overlapping peptides were tested in ex vivo gamma interferon enzyme-linked immunospot assays in 49 patients with culture-confirmed tuberculosis and 38 healthy BCG-vaccinated donors. Forty-five percent (95% confidence interval [CI], 31 to 57%) and 53% (95% CI, 39 to 67%) of the tuberculosis patients responded to Rv3879c and Rv3873, respectively, identifying these proteins as majorM. tuberculosisT-cell antigens in humans, while 35 and 25% of the patients responded to Rv3878 and Rv1989c, respectively. Of the 38 BCG-vaccinated donors, 1 (2.6%) responded to peptides from Rv3878 and Rv3879c, 3 (7.9%) responded to Rv3873, and none responded to Rv1989c. Exclusion of cross-reactive peptides encoded in conserved motifs of Rv3873, a PPE family member, increased its specificity to 97.4%. The high specificity of Rv3879c peptides and nonconserved Rv3873 sequences, together with their moderate sensitivity in tuberculosis patients, identifies these peptides as candidates for inclusion in new T-cell-based tests forM. tuberculosisinfection.
CD4-T-Lymphocyte Interactions with Pneumolysin and Pneumococci Suggest a Crucial Protective Role in the Host Response to Pneumococcal Infection
Authors: Kadioglu Aras , Coward William , Colston M. Joseph , Hewitt Colin R. A. , Andrew Peter W.
Published: April 2004

Previously, we had shown that T cells accumulated in peribronchiolar and perivascular areas of lungs soon after intranasal infection with
Streptococcus pneumoniae
. We have now presented new evidence, using major histocompatibility class II-deficient mice, that CD4 cells are important for early protective immunity. In addition, we have also shown that a population of human CD4 cells migrates towards pneumococci and that in vivo-passaged pneumococci are substantially more potent at inducing migration than in vitro-grown bacteria. This migratory process is unique to a specific population of CD4 cells, is highly reproducible, and is independent of prior CD4 cell activation, and yet the migratory process results in a significant proportion of CD4 cells becoming activated. The production of pneumolysin is a key facet in the induction of migration of CD4 cells by in vivo bacteria, as pneumolysin-deficient bacteria do not induce migration, but the data also show that pneumolysin alone is not sufficient to explain the enhanced migration. Increased CD25 expression occurs during migration, and a higher percentage of cells in the migrated population express gamma interferon or interleukin 4 (IL-4) than in the population that did not migrate. There is evidence that the activation of IL-4 expression occurs during migration.
Nitric Oxide-Mediated Regulation of Gamma Interferon-Induced Bacteriostasis: Inhibition and Degradation of Human Indoleamine 2,3-Dioxygenase
Authors: Hucke Christian , MacKenzie Colin R. , Adjogble Koku D. Z. , Takikawa Osamu , Däubener Walter
Published: April 2004

Tryptophan depletion resulting from indoleamine 2,3-dioxygenase (IDO) activity within the kynurenine pathway is one of the most prominent gamma interferon (IFN-γ)-inducible antimicrobial effector mechanisms in human cells. On the other hand, nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) serves a more immunoregulatory role in human cells and thereby interacts with tryptophan depletion in a number of ways. We investigated the effects of NO on IDO gene transcription, protein synthesis, and enzyme activity as well as on IDO-mediated bacteriostasis in the human epithelial cell line RT4. IFN-γ-stimulated RT4 cells were able to inhibit the growth ofStaphylococcus aureusin an IDO-mediated fashion, and this bacteriostatic effect was abolished by endogenously produced NO. These findings were supported by experiments which showed that IDO activity in extracts of IFN-γ-stimulated cells is inhibited by the chemical NO donors diethylenetriamine diazeniumdiolate, S-nitroso-l-cysteine, and S-nitroso-N-acetyl-d,l-penicillamine. Furthermore, we found that both endogenous and exogenous NO strongly reduced the level of IDO protein content in RT4 cells. This effect was not due to a decrease in IDO gene transcription or mRNA stability. By using inhibitors of proteasomal proteolytic activity, we showed that NO production led to an accelerated degradation of IDO protein in the proteasome. This is the first report, to our knowledge, that demonstrates that the IDO is degraded by the proteasome and that NO has an effect on IDO protein stability.
Flagellin Fusion Proteins as Adjuvants or Vaccines Induce Specific Immune Responses
Authors: Cuadros Camilo , Lopez-Hernandez Francisco J. , Dominguez Ana Lucia , McClelland Michael , Lustgarten Joseph
Published: April 2004

Vaccination is the most efficient prophylaxis against a variety of infectious diseases. New vaccination strategies rely on the incorporation of effective adjuvants, which stimulate the innate immune response and, in turn, activate the adaptive immune response. It is well established that flagellin induces inflammatory responses through the activation of antigen-presenting cells (APCs). In order to evaluate whether flagellin can serve as a carrier for the development of adjuvants or vaccines, we prepared a flagellin-enhanced green fluorescent protein (EGFP) fusion protein. Our results demonstrate that a flagellin-EGFP fusion protein is capable of stimulating APCs, resulting in the maturation of these cells and secretion of proinflammatory cytokines. Furthermore, APCs pulsed with the flagellin-EGFP fusion protein effectively process and present EGFP antigens. More importantly, animals immunized with the flagellin-EGFP fusion protein developed specific anti-EGFP T-cell responses. In contrast, recombinant EGFP was not able to stimulate APCs, nor did it induce a T-cell response. Thus, recombinant-flagellin fusion proteins may be suitable carriers as adjuvants or vaccines for the development of new vaccination strategies to induce and boost immune responses against infectious diseases and cancer.
Proteus mirabilis
Genes That Contribute to Pathogenesis of Urinary Tract Infection: Identification of 25 Signature-Tagged Mutants Attenuated at Least 100-Fold
Authors: Burall Laurel S. , Harro Janette M. , Li Xin , Lockatell C.Virginia , Himpsl Stephanie D. , Hebel J. Richard , Johnson David E. , Mobley Harry L. T.
Published: April 2004

Proteus mirabilis
, a common cause of urinary tract infections (UTI) in individuals with functional or structural abnormalities or with long-term catheterization, forms bladder and kidney stones as a consequence of urease-mediated urea hydrolysis. Known virulence factors, besides urease, are hemolysin, fimbriae, metalloproteases, and flagella. In this study we utilized the CBA mouse model of ascending UTI to evaluate the colonization of mutants of
P. mirabilis
HI4320 that were generated by signature-tagged mutagenesis. By performing primary screening of 2,088
P. mirabilis
transposon mutants, we identified 502 mutants that ranged from slightly attenuated to unrecoverable. Secondary screening of these mutants revealed that 114 transposon mutants were reproducibly attenuated. Cochallenge of 84 of these single mutants with the parent strain in the mouse model resulted in identification of 37 consistently out-competed
P. mirabilis
transposon mutants, 25 of which were out-competed >100-fold for colonization of the bladder and/or kidneys by the parent strain. We determined the sequence flanking the site of transposon insertion in 29 attenuated mutants and identified genes affecting motility, iron acquisition, transcriptional regulation, phosphate transport, urease activity, cell surface structure, and key metabolic pathways as requirements for
P. mirabilis
infection of the urinary tract. Two mutations localized to a ∼42-kb plasmid present in the parent strain, suggesting that the plasmid is important for colonization. Isolation of disrupted genes encoding proteins with homologies to known bacterial virulence factors, especially the urease accessory protein UreF and the disulfide formation protein DsbA, showed that the CBA mouse model and mutant pools are a reliable source of attenuated mutants with mutations in virulence genes.
The Host Cell Chaperone Hsp90 Is Necessary for Cytotoxic Action of the Binary Iota-Like Toxins
Authors: Haug Gerd , Aktories Klaus , Barth Holger
Published: April 2004

The heat shock protein Hsp90 is essential for uptake of the binary actin ADP-ribosylating toxins
Clostridium perfringens
iota-toxin and
Clostridium difficile
transferase into eukaryotic cells. Inhibition of Hsp90 by its specific inhibitor radicicol delayed intoxication of Vero cells by these toxins. A common Hsp90-dependent mechanism for their translocation is discussed.
The Fibrinogen Binding Protein of
Staphylococcus epidermidis
Is a Target for Opsonic Antibodies
Authors: Rennermalm Anna , Nilsson Martin , Flock Jan-Ingmar
Published: April 2004

Antibodies against the fibrinogen binding protein (Fbe) of
Staphylococcus epidermidis
significantly increased macrophage phagocytosis. Antibodies against autolysin E were opsonic but to a lesser extent. Antibodies against a novel, putatively surface-located antigen were unable to enhance phagocytosis. The severity of systemic infection of mice with
S. epidermidis
was reduced if the bacteria were preopsonized with anti-Fbe prior to administration. Fbe is thus a strong candidate for protein vaccination against
S. epidermidis
infection, and antibodies against Fbe can be used to prevent or treat infections caused by
S. epidermidis
.
COMPUTER MODELS OF EARLY LAND PLANT EVOLUTION
Authors: Niklas Karl J.
Published: April 2004

▪ Abstract  Computer models are used to mimic the early evolution of ancient vascular plants (tracheophytes). These models have three components: (a) an N-dimensional domain of all mathematically conceivable ancient morphologies (a morphospace); (b) a numerical assessment of the ability (fitness) of each morphology to intercept light, maintain mechanical stability, conserve water, and produce and disperse spores; and (c) an algorithm that searches the morphospace for successively more fit variants (an adaptive walk). Beginning with the most ancient known plant form, evolution is simulated by locating neighboring morphologies that progressively perform one or more tasks more efficiently. The resulting simulated adaptive walks indicate that early tracheophyte evolution involved optimizing the performance of many tasks simultaneously rather than maximizing the performance of one or only a few tasks individually, and that the requirement for optimization accelerated the tempo of morphological evolution in the Silurian and Devonian.
INFLUENCE OF THE MENDOCINO TRIPLE JUNCTION ON THE TECTONICS OF COASTAL CALIFORNIA
Authors: Furlong Kevin P. , Schwartz Susan Y.
Published: April 2004

▪ Abstract  The migration of the Mendocino triple junction through central and northern California over the past 25–30 million years has led to a profound change in plate interactions along coastal California. The tectonic consequences of the abrupt change from subduction plate interactions north of the triple junction to the development of the San Andreas transform system south of the triple junction can be seen in the geologic record and geophysical observations. The primary driver of this tectonism is a coupling among the subducting Juan de Fuca (Gorda), North American, and Pacific plates that migrates with the triple junction. This coupling leads to ephemeral thickening of the overlying North American crust, associated uplift and subsequent subsidence, and a distinctive sequence of fault development and volcanism.
EVOLUTION OF THE NORTH AMERICAN CORDILLERA
Authors: Dickinson William R.
Published: April 2004

▪ Abstract  The Cordilleran orogen of western North America is a segment of the Circum-Pacific orogenic belt where subduction of oceanic lithosphere has been underway along a great circle of the globe since breakup of the supercontinent Pangea began in Triassic time. Early stages of Cordilleran evolution involved Neoproterozoic rifting of the supercontinent Rodinia to trigger miogeoclinal sedimentation along a passive continental margin until Late Devonian time, and overthrusting of oceanic allochthons across the miogeoclinal belt from Late Devonian to Early Triassic time. Subsequent evolution of the Cordilleran arc-trench system was punctuated by tectonic accretion of intraoceanic island arcs that further expanded the Cordilleran continental margin during mid-Mesozoic time, and later produced a Cretaceous batholith belt along the Cordilleran trend. Cenozoic interaction with intra-Pacific seafloor spreading systems fostered transform faulting along the Cordilleran continental margin and promoted incipient rupture of continental crust within the adjacent continental block.
MODERN ANALOGS IN QUATERNARY PALEOECOLOGY: Here Today, Gone Yesterday, Gone Tomorrow?
Authors: Jackson Stephen T. , Williams John W.
Published: April 2004

▪ Abstract  Modern analog analysis, the comparison of Quaternary fossil pollen assemblages with modern assemblages, has long been a mainstay of paleoecological and paleoclimatic inference. The logic of analogical inference involves a comparative element (comparison of modern and fossil assemblages to select matches and assess goodness of fit) and a causal element (assumption that the relationships between modern vegetation and derivative pollen assemblages are matched by those between ancient vegetation and fossil pollen assemblages). An array of numerical and statistical tools have been developed to ensure objective, consistent, and quantitative assessments of similarity between pollen assemblages. Divergent or convergent relationships between vegetation and pollen assemblages can arise from a variety of sources, composing a potential source of error in analog analysis, but such errors can be anticipated and minimized. Pollen assemblages lacking modern analogs are well documented for the late-glacial period (17,000–10,000 years BP) in eastern North America and other regions. Simulated climates for this period also lacked modern analogs owing to increased seasonality of insolation, lowered CO2, and persistent ice sheets. Most pollen assemblages from the last glacial maximum (23,000–20,000 years BP) in eastern North America have modern analogs, but macrofossil and other evidence suggest that the vegetation may have lacked modern analogs, owing to unique climate realizations and perhaps direct effects of lowered CO2. Better understanding of the nature of past no-analog vegetation, and the underlying causes, will address important issues in ecology and evolutionary biology and help anticipate biotic responses to the no-analog greenhouse world of the near-future.
Intensified exercise training does not alter AMPK signaling in human skeletal muscle
Authors: Clark S. A. , Chen Z.-P. , Murphy K. T. , Aughey R. J. , McKenna M. J. , Kemp B. E. , Hawley J. A.
Published: April 2004

The AMP-activated protein kinase (AMPK) cascade has been linked to many of the acute effects of exercise on skeletal muscle substrate metabolism, as well as to some of the chronic training-induced adaptations. We determined the effect of 3 wk of intensified training (HIT; 7 sessions of 8 × 5 min at 85% V̇o2 peak) in skeletal muscle from well-trained athletes on AMPK responsiveness to exercise. Rates of whole body substrate oxidation were determined during a 90-min steady-state ride (SS) pre- and post-HIT. Muscle metabolites and AMPK signaling were determined from biopsies taken at rest and immediately after exercise during the first and seventh HIT sessions, performed at the same (absolute) pre-HIT work rate. HIT decreased rates of whole body carbohydrate oxidation ( P < 0.05) and increased rates of fat oxidation ( P < 0.05) during SS. Resting muscle glycogen and its utilization during intense exercise were unaffected by HIT. However, HIT induced a twofold decrease in muscle [lactate] ( P < 0.05) and resulted in tighter metabolic regulation, i.e., attenuation of the decrease in the PCr/(PCr + Cr) ratio and of the increase in [AMPfree]/ATP. Resting activities of AMPKα1 and -α2 were similar post-HIT, with the magnitude of the rise in response to exercise similar pre- and post-HIT. AMPK phosphorylation at Thr172on both the α1 and α2 subunits increased in response to exercise, with the magnitude of this rise being similar post-HIT. Acetyl-coenzyme A carboxylase-β phosphorylation was similar at rest and, despite HIT-induced increases in whole body rates of fat oxidation, did not increase post-HIT. Our results indicate that, in well-trained individuals, short-term HIT improves metabolic control but does not blunt AMPK signaling in response to intense exercise.
Glucose-dependent insulinotropic peptide: differential effects on hepatic artery vs. portal vein endothelial cells
Authors: Ding Ke-Hong , Zhong Qing , Xu Jianrui , Isales Carlos M.
Published: April 2004

Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.
Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity
Authors: Frost Robert A. , Nystrom Gerald J. , Lang Charles H.
Published: April 2004

Although an individual's genetic makeup is a major determinant of muscle mass, other influences, such as hormones, cytokines, nutrition, and exercise can also modulate muscle size. IL-6 is an important inflammatory cytokine. Mice that overexpress IL-6 fail to thrive and/or have reduced skeletal muscle mass. The purpose of the present study was to determine whether the stress hormone epinephrine increases inflammatory cytokine expression in skeletal muscle and muscle cells. Infusion of epinephrine in vivo for 2 h increased IL-6 protein (15-fold) and mRNA (40-fold) in skeletal muscle but not in liver. Epinephrine had a similar effect in C2C12muscle cells, where the hormone increased IL-6 protein and mRNA in a dose- and time-dependent manner. Epinephrine-stimulated IL-6 expression was attenuated by the α-adrenergic receptor antagonist phentolamine and completely blocked by either the β1/2-adrenergic receptor antagonist propranalol or the β2-antagonist ICI-118551. The transcriptional inhibitor DRB and the synthetic glucocorticoid dexamethasone also blocked epinephrine-induced IL-6. SP-600125 (a JNK inhibitor) and SB-202190 (a p38 MAP kinase inhibitor) completely blocked epinephrine-induced IL-6 synthesis. Endotoxin and epinephrine given together had a synergistic affect on IL-6 mRNA and protein expression. Trichostatin A (a histone deacetylase inhibitor) blocked both endotoxin- and epinephrine-induced IL-6 expression. These data suggest that epinephrine induces IL-6 synthesis in skeletal muscle in vivo and myocytes in vitro. Epinephrine utilizes predominantly the β1/2-adrenergic receptors to stimulate IL-6 synthesis. Endotoxin and epinephrine synergize to increase IL-6 mRNA expression. Optimal IL-6 synthesis may require both stress kinase and histone deacetylase activity.
Improving Generalization Capabilities of Dynamic Neural Networks
Authors: Galicki Miroslaw , Leistritz Lutz , Zwick Ernst Bernhard , Witte Herbert
Published: April 2004

This work addresses the problem of improving the generalization capabilities of continuous recurrent neural networks. The learning task is transformed into an optimal control framework in which the weights and the initial network state are treated as unknown controls. A new learning algorithm based on a variational formulation of Pontrayagin's maximum principle is proposed. Under reasonable assumptions, its convergence is discussed. Numerical examples are given that demonstrate an essential improvement of generalization capabilities after the learning process of a dynamic network.
Sovereignty Bounded: Public Trusteeship for Common Pool Resources?
Authors: Sand Peter H.
Published: April 2004

In spite of early hopes for a “fading out” of sovereignty in the face of global environmental challenges, recent codifications of international law have confirmed the creeping national enclosure of what were once considered common assets—e.g., exclusive economic zones under the 1982 Law of the Sea Convention, or access to genetic resources from the 1983 International Undertaking via the 1992 Biodiversity Convention to the 2001 Plant Gene Treaty. Yet, because of their explicit limitation and qualification by “common interest” obligations, these expanded sovereign rights of nation states must be considered fiduciary rather than proprietary. Hence, the emerging legal regime is one of international public trusteeship (sometimes referred to as guardianship or stewardship) over a widening range of environmental resources. The article traces the evolution of the trusteeship concept in modern environmental law and its ramifications for international law and governance, as reflected in current proposals suggesting a new environmental mandate for the UN Trusteeship Council.
Termitivore or detritivore? A quantitative investigation into the diet of the East African caecilian Boulengerula taitanus (Amphibia: Gymnophiona: Caeciliidae)
Authors: Gaborieau Olivier , Measey G. John
Published: April 2004

Most caecilians are thought to be generalist predators of soil ecosystem engineers (earthworms, termites and ants), but it has been suggested that members of the East African genus Boulengerula are specialist predators. Surprisingly, in the only detailed study of diet of any Boulengerula, the authors speculated that B. taitanus is partly detritivorous, based on the large amount of organic matter found in the alimentary canal. Here we test the conflicting hypotheses that B.taitanus is a termitivore or detritivore, using the stomach and gut contents of 47 specimens collected in the Taita Hills, Kenya. Termites and earthworms contribute most significantly to diet by number and mass, respectively. These constitute the major dietary items, together with dipteran larvae and other soil macrofauna. Contents of the intestine are mostly soil and organic matter originating from prey items. The mass content of the intestines averages 69% of total gut contents, and is significantly greater than identifiable stomach contents. The null hypotheses that B. taitanus is a generalist and a predator are not rejected.
How Denmark Became Democratic
Authors: Kaspersen Lars Bo
Published: April 2004

In taking a statist perspective inspired by Hegel, Clausewitz and C. Schmitt this article provides an analysis of the period from the early seventeenth century to the mid-nineteenth century, when Denmark evolved towards a liberal-democratic state based on a written constitution. It is argued that Denmark became a democracy as an unintended consequence of military reforms. Whereas most analyses on state formation in early modern Europe contain some form of path dependency, this work argues that the Danish case clearly demonstrates that no path dependency model can in any satisfying sense explain the two crucial years in the formation and change of the Danish state, 1660 (the introduction of the Absolutist rule) and 1849 (the introduction of the liberal-democratic constitution). Consequently, the Danish development challenges commonly held views of state formation processes in Europe.
What is Positive Youth Development?
Authors: Damon William
Published: April 2004

This article explores the recent approach to youth research and practice that has been called positive youth development. The author makes the case that the approach grew out of dissatisfaction with a predominant view that underestimated the true capacities of young people by focusing on their deficits rather than their developmental potentials. The article examines three areas of research that have been transformed by the positive youth approach: the nature of the child; the interaction between the child and the community; and moral growth. It concludes with the point that positive youth development does not simply mean an examination of anything that appears to be beneficial for young people. Rather, it is an approach with strong defining assumptions about what is important to look at if we are to accurately capture the full potential of all young people to learn and thrive in the diverse settings where they live.
Indicators of Child Well-Being: the Promise for Positive Youth Development
Authors: Moore Kristin Anderson , Lippman Laura , Brown Brett
Published: April 2004

In the current U.S. indicators system, measures of child well-being focus primarily on negative outcomes and problems. We measure and track those behaviors that adults wish to prevent. For the most part, the indicators system does not monitor positive development and outcomes. Such a system of child well-being indicators lacks the breadth and balance required in a science-based measurement system. Moreover, it lacks measures of the kinds of constructs that resonate among adolescents themselves and adults. Measures are needed for multiple domains of development, including educational achievement and cognitive attainment, health and safety, social and emotional development, and self-sufficiency. Positive outcomes are often critiqued as soft, highlighting the importance of rigorous conceptualization and measurement, including conceptual clarity and face validity, age appropriate measures, and psychometric rigor. In addition, constructs and measures need to be presented in ways that are understandable to policy makers and the public and that work across varied subgroups and levels of governance. Ideally, comparable measures will be used for indicators, for program evaluation, and in basic research studies of child and adolescent development.
Research and Policing: The Infrastructure and Political Economy of Federal Funding
Authors: Sherman Lawrence W.
Published: April 2004

Despite major progress in social science helping policeto prevent crime, federal funding for police research is atits lowest level in thirty-five years. Only a majorrestructuring of the political economy of criminology seemslikely to revive research with and for the police. Forabout $1 per American per year, federal funding for“Centers for Crime Prevention” could be established inall sixty-seven cities of more than 250,000 people and ineach of the twenty states with no cities that large. Bycreating much stronger grassroots engagement in research,both the consumption and the production of socialscience could be greatly strengthened to improve theeffectiveness and fairness of police practice.
Pharmacokinetics of Montelukast in Asthmatic Patients 6 to 24 Months Old
Authors: Migoya Elizabeth , Kearns Gregory L. , Hartford Alan , Zhao Jamie , van Adelsberg Janet , Tozzi Carol A. , Knorr Barbara , Deutsch Paul
Published: April 2004

Montelukast is a cysteinyl leukotriene receptor antagonist approved for the treatment of asthma for those ages 1 year old to adult. The purpose of this study was to evaluate the pharmacokinetic comparability of a 4‐mg dose of montelukast oral granules in patients >6 to < 24 months old to the 10‐mg approved dose in adults. This was an open‐label study in 32 patients. Population pharmacokinetic parameters included estimates of AUCpop, Cmax, and tmax. Results were compared with estimates from adults (10‐mg film‐coated tablet [FCT]). Dose selection criteria were for the 95% confidence interval (CI) for the AUCpop estimate ratio (pediatric/adult 10 mg FCT) to be within comparability bounds of (0.5, 2.00). The AUCpop ratio and the 95% CI for children compared with adults were within the predefined comparability bounds. Observed plasma concentrations were also similar. Based on systemic exposure of montelukast, a 4‐mg dose of montelukast appears appropriate for children as young as 6 months of age.
Occupation Regimes Alike and Unlike: British, Dutch and French Patterns of Inter-Organizational Control of Foreign Territories
Authors: Lammers Cornelis J.
Published: April 2004

Occupation, in the sense of foreign domination brought about or sustained by force, is nearly always characterized by the use (or threat) of negative sanctions, by some form of authority, and by the application of positive sanctions. Furthermore, loyal elites (auxiliaries legitimized from above) and native elites (legitimized from below) generally play a crucial role in the control of the subjugated populace. Intercultural variations in occupation regimes are illustrated by the historical example of Dutch, British and French patterns of control in the Spanish Netherlands in the early 18th century. Whereas the Dutch and the English preferred indirect rule via native elites, the French tended to favour direct rule by assimilated loyal elites. However, the French and the Dutch practised, albeit in varying ways, ‘close supervision’, while the British displayed a fairly relaxed ‘laissez-faire’ pattern of control. Similar differences were discerned in studies of the colonial administration practices of Britain, France and The Netherlands in Africa and Asia, while Hofstede’s findings concerning the dimensions of culture suggest that the variations in question reflect home-grown styles of organizing. The results can be interpreted with the aid of rational choice theory in the manner of Coleman, Stinchcombe’s theory about the historical insignia of organizational designs and a touch of Weberian thought.
‘A Rounded Picture is What We Need’: Rhetorical Strategies, Arguments, and the Negotiation of Change in a UK Hospital Trust
Authors: Mueller Frank , Sillince John , Harvey Charles , Howorth Chris
Published: April 2004

This article is concerned with the introduction of the agenda of New Public Management (NPM) within the board of a UK Hospital Trust: West London Hospital (WLH). We discuss the literature on New Public Management, including its limitations for analysing the organizational reality of implementing NPM. But we will also be drawing on discourse theory and the literature on rhetoric. The main argument in this article is that in order to understand the reality of the NPM paradigm, we need to study the rhetorical strategies of protagonists involved in the negotiation of the NPM agenda. Rhetorical strategies are means of making general viewpoints more convincing, for example, by comparing ‘our’ organization with similar organizations. Rhetorical strategies show patterns, which reappear in conversations and arguments made by protagonists. Specifically, we identified three rhetorical strategies justifying why and what kind of a more ‘rounded picture’ was required: widening the argument to include national productivity comparisons with other hospitals; widening the argument away from a narrow focus on finance toward a strategic and political perspective; and, lastly, widening the argument to look at innovation in the whole clinical process.
Dynamics of Central Control and Subsidiary Autonomy in the Management of Human Resources: Case-Study Evidence from US MNCs in the UK
Authors: Ferner Anthony , Almond Phil , Clark Ian , Colling Trevor , Edwards Tony , Holden Len , Muller-Camen Michael
Published: April 2004

This article revisits a central question in the debates on the management of multinationals: the balance between centralized policy-making and subsidiary autonomy. It does so through data from a series of case studies on the management of human resources in American multinationals in the UK. Two strands of debate are confronted. The first is the literature on differences between multinationals of different national origins which has shown that US companies tend to be more centralized, standardized, and formalized in their management of human resources. It is argued that the literature has provided unconvincing explanations of this pattern, failing to link it to distinctive features of the American business system in which US multinationals are embedded. The second strand is the wider debate on the balance between centralization and decentralization in multinationals. It is argued that the literature neglects important features of this balance: the contingent oscillation between centralized and decentralized modes of operation and (relatedly) the way in which the balance is negotiated by organizational actors through micro-political processes whereby the external structural constraints on the company are defined and interpreted. In such negotiation, actors’ leverage often derives from exploiting differences between the national business systems in which the multinational operates.
Ocularcentrism and its Others: A Framework for Metatheoretical Analysis
Authors: Kavanagh Donncha
Published: April 2004

There is a contemporary scepticism towards vision-based metaphors in management and organization studies that reflects a more general pattern across the social sciences. In short, there has been a shift away from ocularcentrism. This shift provides a useful basis for metatheoretical analysis of the philosophical discourse that informs organizational analysis. The article begins by briefly discussing the vision-generated, vision-centred interpretation of knowledge, truth, and reality that has characterized the western philosophical tradition. Taking late 18th-century rationalism as the high-point of ocularcentrism, the article then presents a metatheoretical framework based on three trajectories that critiques of ocularcentrism have subsequently taken. The first exposes the limits of the metaphor by, paradoxically, taking it to its limits. The second trajectory seeks to displace the primordial position of the ocular metaphor and replace it with an alternative lexicon based on other human senses. Last, the third trajectory describes how the Enlightenment ocular characterization of the visual and mental worlds has effectively been inverted in the postmodern moment.
Peripheral Vision
Authors: Maruyama Magoroh
Published: April 2004

There are several meta-level considerations which are seldom taken up but are crucial. Two of them are discussed in this article: polyocular vision, in which the differences between images obtained from many angles enable the brain to compute invisible mental coordinates; and illusion of understanding, in which a person is convinced that he or she has a perfect understanding while missing the most important points of others. Job rotation and quasi-rotation help cultivate polyocular vision. On the other hand, concept inbreeding in an organization poses a barrier to polyocular vision. Intellectual outbreeding is facilitated by establishing conceptual ‘free trade zones’ such as the Peripheral Vision section in this journal.
Justice for Looked after Children?
Authors: Taylor Claire
Published: April 2004

Abstract The relationship between experiences of public care and criminal behaviour is frequently referred to in the fields of child care and criminology, but has rarely been empirically explored. This article attempts to highlight something of the complexity of this relationship by drawing on interview data with careleavers, and by discussing policy assumptions relating to children in the care and criminal justice systems. In light of the current policy climate and popular perceptions that routinely link children in care with trouble, the article questions how far justice for looked after children can be achieved.
Re-Meshing Algorithms Applied to Mould Filling Simulations in Resin Transfer Moulding
Authors: Bechet E. , Ruiz E. , Trochu F. , Cuilliere J.-C.
Published: April 2004

In injection moulding processes such as Resin Transfer Moulding (RTM) for example, numerical simulations are usually performed with a fixed mesh, on which the displacement of the flow front is predicted by the numerical algorithm. During the injection, special physical phenomena occur on the front, such as capillary effects inside the fibre tows or heat transfer when the fluid is injected at a different temperature than the mould. In order to approximate these phenomena accurately, it is always better to adapt the mesh to the shape of the flow front. This can be achieved by implementing re-meshing algorithms, which will provide not only more accurate solutions, but also faster calculations. In order to represent precisely the shape of the saturated domain in the cavity, the mesh needs to be non-isotropic in the vicinity of the flow front. The size of the elements along the front is connected to the overall accuracy needed for the simulation; the size in the perpendicular direction governs the accuracy on the position of the moving boundary in time. Since these two constraints on element size are not related, the need for non-isotropic mesh refinement is crucial. In the approach proposed here, the mesh is changed at each time step from a background isotropic mesh used as starting point in the refinement algorithm. The solution needs to be projected on the new mesh after each re-meshing. This amounts to adopting a new filling algorithm, which will be validated by comparison to a standard simulation (without re-meshing) and with experimental data.
Bounds on Elastic Moduli of Multiphase Composite Bodies
Authors: Sharma Rajesh , Ranta Sohan , Ranjan Ashish
Published: April 2004

Minimum and maximum values of the ratio and difference of the values of longitudinal and transverse moduli of a multiphase composite body are obtained in this paper when the moduli of the constituents take values in a given finite interval. A numerical example is presented to test the validity of the results and it is shown that the bounds are useful in interpreting the mechanical behavior of multiphase composite bodies. The constituents of the composite are assumed to be homogeneous and isotropic.
Analysis of the Mold Filling Process on Flip Chip Package
Authors: Shen Y. K. , Chen S. H. , Lee H. C.
Published: April 2004

Flip chip package is the most important technology in IC package in terms of scale, velocity and cost in the development of semiconductor technology and the innovation of computer product. It has the advantage of low cost, low interface and small volume in IC package. This paper describes the analysis package of the solder ball and microchip for mold flow simulation (3D, midplane) and experiment. The numerical simulation of mold filling process is based on the concept of control volume finite element method. The injection point uses the corner, 1/4 side and central injection location. The injection process uses different parameters (mold temperature, injection temperature, injection pressure and injection time). For processing situation, the best result is from central injection, then 1/4 side injection and then corner injection. The results also show that the filling situation for 3D numerical simulation is closer to experiment.
Effective Moduli of Random Short Fiber Composite: A Probabilistic Study
Authors: Sk Latifa , Chakraborty Subrata
Published: April 2004

The behavior of short fiber composites are characterized by scatter in mechanical properties due to randomness in fiber orientation, spacing and packing arrangement etc. Thus probabilistic analysis is essential to study its behavior properly. A simulation method is proposed in the present work for computing statistical property of effective moduli of short fiber composite system in an isotropic matrix phase, appropriate to thin section in a state of plane stress. The effective isotropic properties of the composites derived are in terms of elastic properties of each phase and the volume concentration of the fiber phase. Changes in elastic moduli due to abovementioned parameters are taken into consideration in simulation algorithm. A case study is performed to elucidate the proposed algorithm and comparison is made with the available results.
Random Walk Approach on the Study of Distribution During the Resin Transfer Molding Process
Authors: Shih Ming-Sam , Hourng Lih-Wu , Chang Chih-Yuan
Published: April 2004

The dissolution of microscopic voids trapped between fibers during the resin transfer molding process has been monitored previously by the image analysis technique. However, due to the difficulty of tracing simultaneously the interfaces among resin and several small air pockets in the convectional numerical techniques, the dissolution and distribution of the voids are still uneasily simulated. In this paper, we consider the resin flowing perpendicularly through the fiber bundle. A Monte Carlo-like random walk approach is developed to resolve the time-dependent, free-surface flows and to study the transport of tiny bubbles by tracing the paths of fictitious random walk, colored black or white. By decomposing the Darcy s law, which provides a strong correlation function between ∇P and K/μ, the local displacing probability of random walks can be determined. Being consistent with the experimental observations, the numerical results confirm that the voids can be classified into two types, namely, voids trapped in the fiber bundles and voids distributed among the fiber bundles. Through the proposed model, the simulated results show how certain parameters influence the collapsing rate of void, which is important for the void-free design considerations.
Pediatric Trauma: Current Concepts and Treatments
Authors: Vane Dennis W. , Keller Martin S. , Sartorelli Kennith H. , Miceli Alex P.
Published: April 2004

Injured children represent a complex management problem for the trauma surgeon. Physiologic and psychological factors have been shown to influence outcome; however, more importantly, injury patterns and treatment algorithms differ from those recommended for adults. Children often do well after major injuries, but surgeons must use appropriate treatment to maximize the physiologic responses and the innate healing abilities of the growing child. Historically, surgeons have defined childhood as prepubertal, but a child's physiologic response to injury extends well into the third decade of life, making treatment of a 20-year-old similar to that of a 10-year-old, rather than that of a 40-year-old. The distribution of pediatric trauma facilities across the country has limited the access of the injured child to these centers. Adult centers more often serve as the first and definitive treatment provider for children. This article reviews the current concepts of trauma treatments for children. It is hoped that the adult trauma surgeons caring for injured children might gain information that will be of assistance in their daily practice.
Nerve Agents: A Comprehensive Review
Authors: Wiener Sage W. , Hoffman Robert S.
Published: April 2004

Nerve agents are perhaps the most feared of potential agents of chemical attack. The authors review the history, physical characteristics, pharmacology, clinical effects, and treatment of these agents.