bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretic and Empirical Data-Inclusive Process Characterization
Authors: Bokov Vladimir B.
Published: April 2007

In process characterization the quality of information that is obtained depends directly on the quality of process model. The current quality revolution is now providing a strong stimulus for rethinking and re-evaluating many statistical ideas. Among these are the role of theoretic knowledge and data in statistical inference and some issues in theoretic–empirical modelling. With this concern the paper takes a broad, pragmatic view of statistical inference to include all aspects of model formulation. The estimation of model parameters traditionally assumes that a model has a prespecified known form and takes no account of possible uncertainty regarding model structure. But in practice model structural uncertainty is a fact of life and is likely to be more serious than other sources of uncertainty which have received far more attention. This is true whether the model is specified on subject-matter grounds or when a model is formulated, fitted and checked on the same data set in an iterative interactive way. For that reason novel modelling techniques have been fashioned for reducing model uncertainty. Using available knowledge for theoretic model elaboration the techniques that have been created approximate the exact unknown process model concurrently by accessible theoretic and polynomial empirical functions. The paper examines the effects of uncertainty for hybrid theoretic–empirical models and, for reducing uncertainty, additive and multiplicative methods of model formulation are fashioned. Such modelling techniques have been successfully applied to perfect a steady flow model for an air gauge sensor. Validation of the models elaborated has revealed that the multiplicative modelling approach allows us to attain a satisfactory model with small discrepancy from empirical evidence.
Discrete Time, Discrete State Latent Markov Modelling for Assessing and Predicting Household Acquisitions of Financial Products
Authors: Paas Leonard J. , Vermunt Jeroen K. , Bijmolt Tammo H. A.
Published: April 2007

The paper demonstrates application of the latent Markov model for assessing developments by individuals through stages of a process. This approach is applied by using a database on ownership of 12 financial products and various demographic variables. The latent Markov model derives latent classes, representing household product portfolios, and shows the relationship between class membership and household demographics. The analysis provides insight into switching between the latent classes, reflecting developments of individual household product portfolios, and the effects of demographics on such switches. Based on this, we formulate equations to predict future acquisitions of financial products. The model accurately predicts which product a specific household unit acquires next, for most of the products.
Innovation and Market Structure in the Manufacturing Sector: An Application of Linear Feedback Models*
Authors: Uchida Yuichiro , Cook Paul
Published: April 2007

In recent years, there has been a renewed interest in the relationship between market structure and innovation activities at an industry level. The paper examines the relationship between these for the manufacturing sector in a sample of 33 countries. It applies a recently developed method, based on linear feedback models, and uses cross‐country time‐series data. Despite the relatively small number of observations, the results indicate that domestic competition, external market share, and research and development have a positive effect on innovation activities. The results also suggest that the introduction of the foreign competition may have an initial positive effect on innovation activities, but over time this becomes dissipated.
Enhancing Part‐time Teaching in Higher Education: a Challenge for Institutional Policy and Practice
Authors: Knight Peter , Baume David , Tait Jo , Yorke Mantz
Published: April 2007

Higher education in the UK has seen a steady increase in the numbers of part‐time teachers, yet the way in which they are inducted into teaching and the utilisation of their expertise are under‐researched. This qualitative study of 33 part‐time teachers from several universities suggests that their involvement in higher education should be considered from a fresh perspective, which differs from approaches to the enhancement of university teaching that rely upon simply educating individual teachers to do better by requiring their attendance at formally provided courses and events. While these approaches have their place, modern research on professional learning is increasingly pointing to the view that professional formation is an ecological process that is insufficiently served by the formal provision of learning opportunities. The ecological perspective, which emphasises the part played by the everyday workplace in professional formation, provides a challenge to leaders and managers regarding the development and implementation of institutional policy and practice.
Multinationality and performance: A synthetic review and research agenda
Authors: Li Lei
Published: April 2007

This paper provides a reflective and synthetic review of the literature on the relationship between a firm's multinationality and performance. It revisits the main theories and demonstrates a gradual shift from the traditionally equilibrium‐oriented theorization to the recent dynamics‐oriented perspectives. It also examines the current status of empirical inquiry and identifies some important voids. The following areas are highlighted for further conceptual development and empirical investigation: (1) conceptual refinement and measurement of multinationality as a construct; (2) cost‐efficiency implications of multinationality; (3) impact of internationalization motivations on both multinationality and performance; (4) two‐way relationships between multinationality and performance; and (5) moderating roles of important external and internal contextual factors.
The impact of acquisitions on firm performance: A review of the evidence
Authors: Tuch Christian , O'Sullivan Noel
Published: April 2007

This paper presents a review of empirical research on the impact of acquisitions on firm performance. The evidence suggests that, in the short run, acquisitions have at best an insignificant impact on shareholder wealth. Long‐run performance analysis reveals overwhelmingly negative returns, while the evidence using accounting performance measures is mixed. The review also examines the impact of bid characteristics on performance. The acquisition of hostile targets, transactions that are paid for with cash and acquisitions of larger targets are associated with superior (or at least less negative) performance, while there is mixed evidence on the benefits of related acquisitions. A number of recent studies find that acquirers with superior pre‐bid performance tend to experience significant underperformance in the post‐bid period.
No barriers to fertilization between sympatric colour morphs in the marine species flock Hypoplectrus (Serranidae)
Authors: Whiteman E. A. , Gage M. J. G.
Published: April 2007

Assortative mate choice is, so far, the only demonstrated isolating barrier between colour morphs in fish species flocks, such as freshwater cichlids and marine hamlets, suggesting an important role for sexual selection in speciation. However, there has been little consideration of post‐copulatory mechanisms that are known to influence reproductive isolation in other taxa. Selective pressures through a cost to hybrid matings, or genetic drift, may lead to the evolution of fertilization barriers through gamete incompatability. In cases of incipient speciation, such as the hamlets, complete fertilization blocks may not have evolved. Instead, differential fertilization between species may reduce the success of interspecific fertilizations. We examined the fertilization dynamics of sympatric Hypoplectrus nigricans (black hamlet) and Hypoplectrus puella (barred hamlet). Experimental crosses were performed to score fertilization success in within‐morph and between‐morph crosses. Fertilization success did not differ between self‐fertilized, within‐morph or between‐morph crosses. We therefore found no evidence of post‐mating barriers through sperm:egg incompatibilities and potential for self‐fertilization. Our results are consistent with a mechanism of colour morph divergence based on sexually selected morph mating preferences.
Environmental change and carbon limitation in trees: a biochemical, ecophysiological and ecosystem appraisal
Authors: Millard Peter , Sommerkorn Martin , Grelet Gwen‐Aëlle
Published: April 2007

Contents

Summary
11

I.
Introduction
12

II.
The biochemical scale: the paradox of Rubisco
13

III.
The ecophysiological scale: the profligate use of carbon
16

IV.
The ecosystem scale: how forests respond to environmental change
21

V.
Conclusions
23

Acknowledgements
23

References
23
Iacopo della Quercia scultore Sanese: late Medieval or early Renaissance artist?
Authors: Geddes Helen
Published: April 2007

The work of the Siena‐born sculptor Jacopo della Quercia (b. c. 1370–75 – d. 1438) has often proved difficult to reconcile with early fifteenth‐century artistic trends, and he has often been marginalised in mainstream assessments of early Italian sculpture. Quercia has commonly been perceived as anomalous, neither belonging wholly to the Trecento, nor conforming unequivocally to the characterization of a ‘Renaissance’ artist, despite being a contemporary of Donatello, Lorenzo Ghiberti, and Masaccio. This is a view compounded by his never having found patronage in Florence. The paper examines the changing critical reception of Quercia's sculptures, from the later fifteenth century, to Giorgio Vasari in the sixteenth, through to the modern literature, thus charting the changing perception of his art. An analysis of the extent to which his sculptural works conform to the preoccupations of Renaissance art, in his treatment of the human body, of perspective, the study of the antique, and in the study of nature, is presented. The paper argues that it is the somewhat artificial and limiting definitions imposed by art historical periods, and an emphasis on artists working in Florence, that have obscured and hindered direct appreciation and understanding of Quercia's great achievements.
Between Italy and Spain: cultural interchange in the Roman career of Sebastiano del Piombo
Authors: Baker‐Bates Piers
Published: April 2007

High Renaissance Rome has been envisioned as hermetic – or at least as being influential only in the Italian peninsula, until the traumatic effects of the Sack of 1527 dispersed throughout Europe the community of artists gathered there. In contrast to this traditionally Italo‐centric view, the export trade in artistic ideas, if not in physical objects, was flourishing throughout the period 1492–1534. Given Rome's position as the diplomatic centre of the Italian peninsula and the varied nationalities of the personnel employed in the Curia, the achievements of High Renaissance culture were always easily accessible to foreign patrons. In turn, as the export market flourished, it encouraged other ‘foreigners’ (a definition including both Italians and non‐Italians alike) and the aesthetics of Rome became a standard by which the prestige and culture of an individual could be measured.

No particular group of ‘foreigners’ was better placed to exploit this than the Spanish, already established for many years in the south of Italy and now the growing power throughout the whole peninsula. Spaniards, clerical or secular, were a permanent feature of the Roman Court and among the most prominent was the royal ambassador. This post from 1506–21, the apex of the High Renaissance, was held by the Valencian aristocrat, Don Jeronimo de Vich y Vallterra. Vich brought to Valencia not only two works by Sebastiano del Piombo but also designs for an entirely contemporary palazzo. In these activities not only was he consciously emulating the Borgia, who had first brought the Italian Renaissance to Valencia, but in turn his imports provided a model for the succeeding generations of Valencian artists to emulate.
A recalibration of the garnet‐olivine geothermometer and a new geobarometer for garnet peridotites and garnet‐olivine‐plagioclase‐bearing granulites
Authors: WU C. M. , ZHAO G. C.
Published: April 2007

The garnet‐olivine Fe‐Mg exchange geothermometer and the garnet‐olivine‐plagioclase geobarometer have been simultaneously calibrated using reversed experimental data based on the model reactions
image

and
image

between 900 and 1500 °C at 9.1–95.0 kbar and between 4.7 and 7.0 kbar at 750–1050 °C, respectively. The resulting garnet‐olivine thermometer reproduces experimental temperatures mostly within ±75 °C and the garnet‐olivine‐plagioclase barometer reproduces experimental pressures well within ±0.19 kbar. These new thermobarometers use the same garnet and olivine activity models and are thermodynamically consistent. Application of these thermobarometers to garnet peridotites from mantle xenoliths, orogenic garnet peridotites over the world and the Adirondack olivine‐bearing metagabbros yielded reasonable P–T results. The present garnet‐olivine thermometer can be used to measure medium‐high‐grade to ultrahigh‐grade, low‐pressure to ultrahigh–high‐pressure garnet peridotites and metagabbros, whereas the garnet‐olivine‐plagioclase barometer has limited application to garnet‐olivine‐plagioclase‐bearing granulites.
The crystal structure of the ring‐hydroxylating dioxygenase from Sphingomonas CHY‐1
Authors: Jakoncic Jean , Jouanneau Yves , Meyer Christine , Stojanoff Vivian
Published: April 2007

The ring‐hydroxylating dioxygenase (RHD) from Sphingomonas CHY‐1 is remarkable due to its ability to initiate the oxidation of a wide range of polycyclic aromatic hydrocarbons (PAHs), including PAHs containing four‐ and five‐fused rings, known pollutants for their toxic nature. Although the terminal oxygenase from CHY‐1 exhibits limited sequence similarity with well characterized RHDs from the naphthalene dioxygenase family, the crystal structure determined to 1.85 Å by molecular replacement revealed the enzyme to share the same global α3β3 structural pattern. The catalytic domain distinguishes itself from other bacterial non‐heme Rieske iron oxygenases by a substantially larger hydrophobic substrate binding pocket, the largest ever reported for this type of enzyme. While residues in the proximal region close to the mononuclear iron atom are conserved, the central region of the catalytic pocket is shaped mainly by the side chains of three amino acids, Phe350, Phe404 and Leu356, which contribute to the rather uniform trapezoidal shape of the pocket. Two flexible loops, LI and LII, exposed to the solvent seem to control the substrate access to the catalytic pocket and control the pocket length. Compared with other naphthalene dioxygenases residues Leu223 and Leu226, on loop LI, are moved towards the solvent, thus elongating the catalytic pocket by at least 2 Å. An 11 Å long water channel extends from the interface between the α and β subunits to the catalytic site. The comparison of these structures with other known oxygenases suggests that the broad substrate specificity presented by the CHY‐1 oxygenase is primarily due to the large size and particular topology of its catalytic pocket and provided the basis for the study of its reaction mechanism.
From functional genomics to systems biology
Authors: Ivakhno Sergii
Published: April 2007

This review discusses the talks presented at the third EMBL Biennial Symposium, From functional genomics to systems biology, held in Heidelberg, Germany, 14–17 October 2006. Current issues and trends in various subfields of functional genomics and systems biology are considered, including analysis of regulatory elements, signalling networks, transcription networks, protein–protein interaction networks, genetic interaction networks, medical applications of DNA microarrays, and metagenomics. Several technological advances in the fields of DNA microarrays, identification of regulatory elements in the genomes of higher eukaryotes, and MS for detection of protein interactions are introduced. Major directions of future systems biology research are also discussed.
Role of receptor‐mediated endocytosis, endosomal acidification and cathepsin D in cholera toxin cytotoxicity
Authors: El Hage Tatiana , Merlen Clémence , Fabrega Sylvie , Authier François
Published: April 2007

Using the in situ liver model system, we have recently shown that, after cholera toxin binding to hepatic cells, cholera toxin accumulates in a low‐density endosomal compartment, and then undergoes endosomal proteolysis by the aspartic acid protease cathepsin‐D [Merlen C, Fayol‐Messaoudi D, Fabrega S, El Hage T, Servin A, Authier F (2005) FEBS J272, 4385–4397]. Here, we have used a subcellular fractionation approach to address the in vivo compartmentalization and cytotoxic action of cholera toxin in rat liver parenchyma. Following administration of a saturating dose of cholera toxin to rats, rapid endocytosis of both cholera toxin subunits was observed, coincident with massive internalization of both the 45 kDa and 47 kDa Gsα proteins. These events coincided with the endosomal recruitment of ADP‐ribosylation factor proteins, especially ADP‐ribosylation factor‐6, with a time course identical to that of toxin and the A subunit of the stimulatory G protein (Gsα) translocation. After an initial lag phase of 30 min, these constituents were linked to NAD‐dependent ADP‐ribosylation of endogenous Gsα, with maximum accumulation observed at 30–60 min postinjection. Assessment of the subsequent postendosomal fate of internalized Gsα revealed sustained endolysosomal transfer of the two Gsα isoforms. Concomitantly, cholera toxin increased in vivo endosome acidification rates driven by the ATP‐dependent H+‐ATPase pump and in vitro vacuolar acidification in hepatoma HepG2 cells. The vacuolar H+‐ATPase inhibitor bafilomycin and the cathepsin D inhibitor pepstatin A partially inhibited, both in vivo and in vitro, the cAMP response to cholera toxin. This cathepsin D‐dependent action of cholera toxin under the control of endosomal acidity was confirmed using cellular systems in which modification of the expression levels of cathepsin D, either by transfection of the cathepsin D gene or small interfering RNA, was followed by parallel changes in the cytotoxic response to cholera toxin. Thus, in hepatic cells, a unique endocytic pathway was revealed following cholera toxin administration, with regulation specificity most probably occurring at the locus of the endosome and implicating endosomal proteases, such as cathepsin D, as well as organelle acidification.
Directed evolution of trimethoprim resistance in Escherichia coli
Authors: Watson Morgan , Liu Jian‐Wei , Ollis David
Published: April 2007

Directed evolution is a useful tool in the study of enzymes. It is used in this study to investigate the means by which resistance to the antibiotic trimethoprim develops in dihyrofolate reductase from Escherichia coli. Mutants with clinical levels of resistance were obtained after only three generations. After four generations of directed evolution, several mutants were characterized, along with some point mutants made to investigate amino acid changes of interest. Several mutations were found to grant resistance to trimethoprim, both by reducing the binding affinity of the enzyme for the drug, and by increasing the activity of the enzyme.
Accuracy of electrocardiogram interpretation improves with emergency medicine training
Authors: Hoyle Rachel J , Walker Katherine J , Thomson Graeme , Bailey Michael
Published: April 2007

Objective:  To assess whether electrocardiogram (ECG) interpretation accuracy improves with advancing years of emergency medicine training.

Methods:  A prospective cross‐sectional double‐blinded study of emergency medicine trainees attending teaching sessions in ACEM accredited Victorian hospitals. Subjects completed a survey about level of training, rotations completed and ECG training. They were then asked for the ‘main diagnosis’ on 10 clinically significant ECG. Those in their fourth year of advanced training onwards, or in active preparation for fellowship examination (senior trainees) were compared with trainees in earlier years (other trainees).

Results:  There were 122 trainees surveyed in total. In the present study, 48/122 were senior trainees and 74/122 were other trainees. The overall accuracy of ECG interpretation was 67.5% (95% confidence interval [CI] 63.2–71.8%) for the senior trainees and 49.6% (95% CI 45.2–53.9%) for the others. Results for some of the individual ECG were: left bundle branch block: 81.3% (95% CI 69.9–92.6%) seniors and 58.1% (95% CI 46.6–69.7%) others; ventricular tachycardia: 43.8% (95% CI 29.3–58.2%) seniors and 37.8% (95% CI 26.5–49.2%) others; and ventricular fibrillation: 70.8% (95% CI 57.6–84.1%) seniors and 63.5% (95% CI 52.2–74.9%) others.

Conclusion:  There is an improvement in ECG interpretation accuracy with advancing years of emergency medicine training in Victoria. There exists, however, a low level of accuracy for some critical ECG diagnoses. There is a call by trainees for more formalized and regular ECG education to begin earlier in their training.
piRNAs in the Germ Line
Authors: Lin Haifan
Published: April 2007

Small noncoding RNAs have emerged as potent regulators of gene expression at both transcriptional and posttranscriptional levels. Recently, a class of small RNAs that interact with Piwi proteins has been discovered in the mammalian germ line and
Drosophila.
These Piwi-interacting RNAs (piRNAs) represent a distinct small RNA pathway.
Comment on "Ongoing Adaptive Evolution of
ASPM
, a Brain Size Determinant in
Homo sapiens
"
Authors: Yu Fuli , Hill R. Sean , Schaffner Stephen F. , Sabeti Pardis C. , Wang Eric T. , Mignault Andre A. , Ferland Russell J. , Moyzis Robert K. , Walsh Christopher A. , Reich David
Published: April 2007

Mekel-Bobrov
et al
. (Reports, 9 September 2005, p. 1720) suggested that
ASPM
, a gene associated with microcephaly, underwent natural selection within the last 500 to 14,100 years. Their analyses based on comparison with computer simulations indicated that
ASPM
had an unusual pattern of variation. However, when we compare
ASPM
empirically to a large number of other loci, its variation is not unusual and does not support selection.
The Maternal-Zygotic Transition: Death and Birth of RNAs
Authors: Schier Alexander F.
Published: April 2007

Maternal gene products drive early development when the newly formed embryo is transcriptionally inactive. During the maternal-zygotic transition, embryonic transcription is initiated and many maternal RNAs are degraded. Multiple mechanisms regulate the birth of zygotic RNAs and the death of maternal RNAs. Genome activation appears to rely in part on the sequestration of transcriptional repressors by the exponentially increasing amount of DNA during cleavage divisions. Maternal RNA degradation is induced by the binding of proteins and microRNAs to the 3′ untranslated region of target RNAs.
The Most Fragile of Newborns
Authors: Lorch Scott A.
Published: April 2007

Baby at Risk
. The Uncertain Legacies of Medical Miracles for Babies, Families, and Society.
By Ruth Levy Guyer
. Capital Books, Sterling, VA, 2006. 181 pp. $22.95. ISBN 9781933102269.

Guyer discusses the benefits and costs of neonatal intensive care and examines the question of who should make the decisions about high-tech interventions.
Molecular Discrimination of Atypical Bovine Spongiform Encephalopathy Strains from a Geographical Region Spanning a Wide Area in Europe
Authors: Jacobs Jorg G. , Langeveld Jan P. M. , Biacabe Anne-Gaëlle , Acutis Pier-Luigi , Polak Miroslaw P. , Gavier-Widen Dolores , Buschmann Anne , Caramelli Maria , Casalone Cristina , Mazza Maria , Groschup Martin , Erkens Jo H. F. , Davidse Aart , van Zijderveld Fred G. , Baron Thierry
Published: April 2007

Transmissible spongiform encephalopathy strains can be differentiated by their behavior in bioassays and by molecular analyses of the disease-associated prion protein (PrP) in a posttranslationally transformed conformation (PrP
Sc
). Until recently, isolates from cases of bovine spongiform encephalopathy (BSE) appeared to be very homogeneous. However, a limited number of atypical BSE isolates have recently been identified upon analyses of the disease-associated proteinase K (PK) resistance-associated moiety of PrP
Sc
(PrP
res
), suggesting the existence of at least two additional BSE PrP
res
variants. These are defined here as the H type and the L type, according to the higher and lower positions of the nonglycosylated PrP
res
band in Western blots, respectively, compared to the position of the band in classical BSE (C-type) isolates. These molecular PrP
res
variants, which originated from six different European countries, were investigated together. In addition to the migration properties and glycosylation profiles (glycoprofiles), the H- and L-type isolates exhibited enhanced PK sensitivities at pH 8 compared to those of the C-type isolates. Moreover, H-type BSE isolates exhibited differences in the binding of antibodies specific for N- and more C-terminal PrP regions and principally contained two aglycosylated PrP
res
moieties which can both be glycosylated and which is thus indicative of the existence of two PrP
res
populations or intermediate cleavage sites. These properties appear to be consistent within each BSE type and independent of the geographical origin, suggesting the existence of different BSE strains in cattle. The choice of three antibodies and the application of two pHs during the digestion of brain homogenates provide practical and diverse tools for the discriminative detection of these three molecular BSE types and might assist with the recognition of other variants.
Fatal Echovirus 18 Leukoencephalitis in a Child
Authors: Brunel Delphine , Jacques Jérôme , Motte Jacques , Andréoletti Laurent
Published: April 2007

Rare cases of leukoencephalitis have been reported in infants with documented enterovirus (EV) central nervous system (CNS) infections. A case of fatal encephalitis with white matter lesions caused by echovirus 18 is described, and it highlights the role of EV CNS infection as a potential cause of leukoencephalitis in infants.
Molecular Epidemiology and Clinical Manifestations of Viral Gastroenteritis in Hospitalized Pediatric Patients in Northern Taiwan
Authors: Chen Shih-Yen , Chang Yu-Chung , Lee Yun-Shien , Chao Hsun-Chin , Tsao Kuo-Chien , Lin Tzou-Yien , Ko Tzu-Yin , Tsai Chi-Neu , Chiu Cheng-Hsun
Published: April 2007

By reverse transcription-PCR or PCR, among 257 children with nonbacterial acute gastroenteritis (AGE), rotavirus, norovirus, astrovirus, enteric adenovirus, and multiple viruses were identified in 78 (30.4%), 21 (8.2%), 7 (2.7%), 51 (19.8%), and 53 (20.6%) patients, respectively. Higher disease severity was found for AGE caused by multiple viruses and by rotavirus alone. The majority of rotaviruses isolated from 2004 to 2006 belonged to genotypes G1 (20.4%), G2 (16.5%), G3 (27.2%), and G9 (21.4%).
Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases
Authors: Qian Li-Wu , Xie Jianping , Ye Fengchun , Gao Shou-Jiang
Published: April 2007

Matrix metalloproteinases (MMPs) play important roles in cancer invasion, angiogenesis, and inflammatory infiltration. Kaposi's sarcoma is a highly disseminated angiogenic tumor of proliferative endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we showed that KSHV infection increased the invasiveness of primary human umbilical vein endothelial cells (HUVEC) in a Matrigel-based cell invasion assay. KSHV-induced cell invasion was abolished by an inhibitor of MMPs, BB-94, and occurred in both autocrine- and paracrine-dependent fashions. Analysis by zymography and Western blotting showed that KSHV-infected HUVEC cultures had increased secretion of MMP-1, -2, and -9. KSHV increased the secretion of MMP-2 within 1 h following infection without upregulating its mRNA expression level. In contrast, the secretion of MMP-1 and -9 was not increased until 6 h after KSHV infection and was correlated with the upregulation of their mRNA expression levels. Promoter analysis by reporter assays and electrophoretic mobility shift assays identified an AP-1
cis
-element as the dominant KSHV-responsive site in the MMP-1 promoter. Together, these results suggest that KSHV infection modulates the production of multiple MMPs to increase cell invasiveness and thus contributes to the pathogenesis of KSHV-induced malignancies.
Coxsackievirus B3 Proteins Directionally Complement Each Other To Downregulate Surface Major Histocompatibility Complex Class I
Authors: Cornell Christopher T. , Kiosses William B. , Harkins Stephanie , Whitton J. Lindsay
Published: April 2007

Picornaviruses carry a small number of proteins with diverse functions that subvert and exploit the host cell. We have previously shown that three coxsackievirus B3 (CVB3) proteins (2B, 2BC, and 3A) target the Golgi complex and inhibit protein transit. Here we investigate these effects in more detail and evaluate the distribution of major histocompatibility complex (MHC) class I molecules, which are critical mediators of the CD8
+
T-cell response. We report that concomitant with viral protein synthesis, MHC class I surface expression is rapidly downregulated during infection. However, this phenomenon may not result solely from inhibition of anterograde trafficking; we propose a new mechanism whereby the CVB3 2B and 2BC proteins upregulate the internalization of MHC class I (and possibly other surface proteins), perhaps by focusing of endocytic vesicles at the Golgi complex. Thus, our findings indicate that CVB3 carries at least three nonstructural proteins that directionally complement one another; 3A disrupts the Golgi complex to inhibit anterograde transport, while 2B and/or 2BC upregulates endocytosis, rapidly removing proteins from the cell surface. Taken together, these effects may render CVB3-infected cells invisible to CD8
+
T cells and untouchable by many antiviral effector molecules. This has important implications for immune evasion by CVB3.
Effects of Viral Strain, Transgene Position, and Target Cell Type on Replication Kinetics, Genomic Stability, and Transgene Expression of Replication-Competent Murine Leukemia Virus-Based Vectors
Authors: Paar Matthias , Schwab Sonja , Rosenfellner Doris , Salmons Brian , Günzburg Walter H. , Renner Matthias , Portsmouth Daniel
Published: April 2007

The limited efficiency of in vivo gene transfer by replication-deficient retroviral vectors remains an obstacle to achieving effective gene therapy for solid tumors. One approach to circumvent this problem is the use of replication-competent retroviral vectors. However, the application of such vectors is at a comparatively early stage and the effects which virus strain, transgene cassette position, and target cell can exert on vector spread kinetics, genomic stability, and transgene expression levels remain to be fully elucidated. Thus, in this study a panel of vectors allowing the investigation of different design features on an otherwise genetically identical background were analyzed with respect to these readout parameters in cultures of both murine and human cells and in preformed tumors in nude mice. The obtained data revealed that (i) Moloney murine leukemia virus (Mo-MLV)-based vectors spread with faster kinetics, drive higher levels of transgene expression, and are more stable than equivalent Akv-MLV-based vectors; (ii) vectors containing the transgene cassette directly downstream of the envelope gene are genomically more stable than those containing it within the 3′-long terminal repeat U3 region; and (iii) the genomic stability of both strains seems to be cell line dependent.
Activated CD34-Derived Langerhans Cells Mediate Transinfection with Human Immunodeficiency Virus
Authors: Fahrbach Kelly M. , Barry Sheila M. , Ayehunie Seyoum , Lamore Sarah , Klausner Mitchell , Hope Thomas J.
Published: April 2007

Langerhans cells (LCs) are a subset of dendritic cells (DCs) that reside within epidermal and mucosal tissue. Because of their location, LCs are potentially the first cells to encounter human immunodeficiency virus (HIV) during sexual transmission. We report that LCs purified from CD34
+
-derived DCs can facilitate the transinfection of target cells but only after activation. Virions were observed in an intracellular compartment that contains several tetraspanins, in addition to the unique LC markers langerin and CD1a. This reveals that the trafficking of HIV within LCs is reminiscent of that which occurs in mature monocyte-derived DCs and that it varies with the activation state of the cell. The observation that activated LCs can mediate transinfection suggests a potential role for these cells in the known increase in HIV transmission associated with sexually transmitted infections that would cause inflammation of the genital lining.
Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein
Authors: Kochs Georg , García-Sastre Adolfo , Martínez-Sobrido Luis
Published: April 2007

The replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-α/β) system. This virus-host interplay is dependent on the production of IFN-α/β and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-β promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.
Prion Protein Alleles Showing a Protective Effect on the Susceptibility of Sheep to Scrapie and Bovine Spongiform Encephalopathy
Authors: Vaccari Gabriele , D'Agostino Claudia , Nonno Romolo , Rosone Francesca , Conte Michela , Di Bari Michele Angelo , Chiappini Barbara , Esposito Elena , De Grossi Luigi , Giordani Francesco , Marcon Stefano , Morelli Luisella , Borroni Renata , Agrimi Umberto
Published: April 2007

The susceptibility of sheep to classical scrapie and bovine spongiform encephalopathy (BSE) is mainly influenced by prion protein (PrP) polymorphisms A136V, R154H, and Q171R, with the ARR allele associated with significantly decreased susceptibility. Here we report the protective effect of the amino acid substitution M137T, I142K, or N176K on the ARQ allele in sheep experimentally challenged with either scrapie or BSE. Such observations suggest the existence of additional PrP alleles that significantly decrease the susceptibility of sheep to transmissible spongiform encephalopathies, which may have important implications for disease eradication strategies.
How exposure information can enhance our understanding of child traffic “death leagues”
Authors: Christie Nicola , Cairns Sally , Towner Elizabeth , Ward Heather
Published: April 2007

Objectives:To explore whether population-based fatality rates and measures of traffic exposure can be combined to provide a more comprehensive measure of safety. To illustrate how this could be achieved using surveys from a range of Organisation for Economic Cooperation and Development (OECD) countries. To discuss why exposure is important.

Design and setting:Fatality data were obtained from the International Road Traffic and Accident Database and travel data from surveys among government transport administrations in each country.

Methods:Comparable exposure data were obtained for children aged 10–14 years from the UK, the USA, Germany, The Netherlands, Norway, Sweden, Switzerland and New Zealand. Fatality rates for children travelling as pedestrians, cyclists and car occupants were calculated based on (1) per head of population and (2) a combination of rate per head population and per kilometre travelled.

Results:In this study, exposure-based fatality rates suggest a more polarized distribution rather than a graduated league. The USA and the UK were at the lower end of the table for child pedestrian safety; Germany for car-occupant safety, Sweden and New Zealand performed less well. For cycling, the inclusion of exposure data considerably changes positions within the table. Countries with higher cycling levels like The Netherlands perform better than those with low levels like the UK and New Zealand.

Conclusions:Exposure-based fatality rates can help us to understand whether policies reduce exposure or whether they increase safety, given a similar level of exposure. Data need to be harmonized across OECD countries for a better understanding of the risks and links between health and sustainable travel.
Pediatricians’ involvement in gun injury prevention
Authors: Olson L M , Christoffel K K , O’Connor K G
Published: April 2007

Background:Injuries from small arms are of concern internationally. The health perspective is an emerging aspect of international work to reduce these injuries. This aspect has been evident in US firearm injury prevention work for over a decade, exhibited by strong statements from the American Academy of Pediatrics (AAP) to remove firearms from children’s environments.

Objectives:To assess trends among US pediatricians related to firearm injury prevention counseling practices and attitudes toward gun legislation.

Design:National random sample, mailed surveys of AAP members: (1) 1994 (response rate  = 68.9%, n = 982); (2) 2000 (response rate  = 62.4%, n = 922). χ2Tests were used to assess bivariate relationships and logistic regression to assess multivariate relationships regarding counseling practices.

Results:Respondents in both years believed that violence prevention should be a priority for pediatricians (91.4% and 92.0%) and reported always or sometimes recommending handgun removal from the home (46.2% and 55.9%, respectively). In 2000, 74% of the respondents were comfortable discussing firearm safety; fewer thought they had sufficient training (32.7%) or time (27.5%) to discuss firearms. In 1994 and 2000, the likelihood of counseling on handgun removal was positively related to recent experience treating a gun injury, female sex and not owning a gun. In both years, >80% of pediatricians thought that gun control legislation or regulations would reduce injury and death.

Conclusions:US pediatricians continue to adopt policies promoting gun injury prevention. The practices and attitudes of pediatricians may be important for public education strategies regarding firearm injury prevention in the US and internationally.
A risky treat: exploring parental perceptions of the barriers to seating their children in the rear seats of passenger vehicles
Authors: Lennon Alexia
Published: April 2007

Background:Sitting in the rear seat of a vehicle rather than in the front seat reduces children’s risk of injury or death by ⩾35% in the event of a crash. As road trauma is a leading cause of child morbidity and mortality in highly motorised nations, even in countries where restraint use is high, encouraging parents to place children in the rear seats of vehicles offers a low-cost avenue to improving children’s overall health. However, little is known about the factors that affect parents’ decisions about seating positions.

Objective:To explore parental perceptions of barriers to placing their children in the rear seat of passenger vehicles whenever possible.

Design and subjects:Focus group discussions were held with urban parent-drivers to elicit their concerns about children’s car safety and barriers to rear-seat use.

Results:Most parents had a rule that children should sit in the rear seat. Parents said that they relaxed these rules for a variety of reasons including social pressure, perceptions of the trip as short and because children regard sitting in the front seat as a treat. Parenting style, child cooperativeness, social pressure and inability to justify the risk of injury were identified as barriers to rear-seat travel.

Conclusions:Effective interventions to increase the proportion of children travelling in the rear seat should address parents’ experiences of pressure to relax seating rules and risk perception, as well as provide strategies that support sound parental safety decisions.
“Risk Watch”: Cluster randomised controlled trial evaluating an injury prevention program
Authors: Kendrick Denise , Groom Lindsay , Stewart Jane , Watson Michael , Mulvaney Caroline , Casterton Rebecca
Published: April 2007

Objective:to evaluate the effectiveness of a school-based injury prevention program.

Design:Cluster randomised controlled trial.

Setting:20 primary schools in Nottingham, UK.

Participants:459 children aged 7 to 10 years.

Intervention:The “Risk Watch” program delivered by teachers, aimed at improving bike and pedestrian, falls, poisoning and fire and burns safety.

Main outcome measures:Safety knowledge, observed safety skills and self-reported safety behaviour.

Results:At follow-up, intervention group children correctly answered more fire and burn prevention knowledge questions than control group children (difference between means 7.0% (95% CI 1.5% to12.6%)). Children in intervention group schools were more likely to know the correct actions to take if clothes catch fire and the correct way to wear a cycle helmet (difference between school means 35.3% (95% CI 22.7% to 47.9%) and 6.3% (95% CI 1.4% to 11.1%) respectively). They were also more likely to know the correct actions to take in a house fire and on finding tablets (OR 2.80 (95% CI 1.08 to 7.22) and OR 3.50 (95% CI 1.18 to 10.38) respectively) and correctly demonstrated more safety skills than control group children (difference between means 11.9% (95% CI 1.4% to 22.5%)). There was little evidence to suggest the first year of the program impacted on self-reported safety behaviours.

Conclusions:The Risk Watch program delivered by teachers in primary schools increased some aspects of children’s safety knowledge and skills and primary schools should consider delivering this program. Longer term, larger scale evaluations are required to examine retention of knowledge and skills and impact on safety behaviours and child injury rates.
ALGEBRAS OF UNBOUNDED OPERATORS AND PHYSICAL APPLICATIONS: A SURVEY
Authors: BAGARELLO F.
Published: April 2007

After a historical introduction on the standard algebraic approach to quantum mechanics of large systems we review the basic mathematical aspects of the algebras of unbounded operators. After that we discuss in some details their relevance in physical applications.
BIFURCATION CURVES OF SUBHARMONIC SOLUTIONS AND MELNIKOV THEORY UNDER DEGENERACIES
Authors: GENTILE GUIDO , BARTUCCELLI MICHELE V. , DEANE JONATHAN H. B.
Published: April 2007

We study perturbations of a class of analytic two-dimensional autonomous systems with perturbations depending periodically on time; for instance one can imagine a periodically driven or forced system with one degree of freedom. In the first part of the paper, we revisit a problem considered by Chow and Hale on the existence of subharmonic solutions. In the analytic setting, under more general (weaker) conditions on the perturbation, we prove their results on the bifurcation curves dividing the region of non-existence from the region of existence of subharmonic solutions. In particular our results apply also when one has degeneracy to the first order — i.e. when the subharmonic Melnikov function is identically constant. Moreover we can deal as well with the case in which degeneracy persists to arbitrarily high orders, in the sense that suitable generalizations to higher orders of the subharmonic Melnikov function are also identically constant. The bifurcation curves consist of four branches joining continuously at the origin, where each of them can have a singularity (although generically they do not). The branches can form a cusp at the origin: we say in this case that the curves are degenerate as the corresponding tangent lines coincide. The method we use is completely different from that of Chow and Hale, and it is essentially based on the proof of convergence of the perturbation theory. It also allows us to treat the Melnikov theory in degenerate cases in which the subharmonic Melnikov function is either identically vanishing or has a zero which is not simple. This is investigated at length in the second part of the paper. When the subharmonic Melnikov function has a non-simple zero, we consider explicitly the case where there exist subharmonic solutions, which, although not analytic, still admit a convergent fractional series in the perturbation parameter.
A DEGENERACY THEOREM FOR MEROMORPHIC MAPPINGS WITH MOVING TARGETS
Authors: TAN TRAN VAN
Published: April 2007

The purpose of this article is to prove a degeneracy theorem for meromorphic mappings of ℂm into ℂPn with (2n + 2) moving targets.
CONSERVING THE LEPTON NUMBER Le-Lμ-LτIN THE EXACT SOLUTION OF A 3-3-1 GAUGE MODEL WITH RIGHT-HANDED NEUTRINOS
Authors: PALCU ADRIAN
Published: April 2007

In this paper we consider a plausible scenario with conserved lepton number L = Le-Lμ-Lτwithin the framework of the exact solution of a particular 3-3-1 gauge model. We discuss the consequences of conserving this global leptonic symmetry from the viewpoint of the neutrino mass matrix constructed via special Yukawa terms (involving tensor products among Higgs triplets). We prove that the actual experimental data can naturally be reproduced by our scenario since soft breaking terms with respect to this lepton symmetry are properly introduced. As a consequence, our solution predicts for the neutrino sector the correct mass splitting ratio [Formula: see text], the inverted mass hierarchy, the correct values for the observed mixing angles ( sin2θ23≃0.5 and sin2θ12= 0.31) and the absolute mass of the lightest neutrino (m0~ 0.001 eV) independent of the breaking scale of the model.
DARK MATTER CANDIDATE FROM CONFORMALITY
Authors: FRAMPTON P. H.
Published: April 2007

Abelian quiver gauge theories provide candidates for the conformality approach to physics beyond the standard model which possess novel cancellation mechanisms for quadratic divergences. A Z2 symmetry ( R parity) can be imposed and leads naturally to a dark matter candidate which is the Lightest Conformality Particle (LCP), a neutral spin-1 / 2 state with weak interaction annihilation cross-section, mass in the 100 GeV region and relic density of non-baryonic dark matter Ωdm which can be consistent with the observed value Ωdm≃0.24.