bluuebunny/crossref_metadata_2025 huggingface dataset:
Vesicular Stomatitis Virus Matrix Protein Impairs CD1d-Mediated Antigen Presentation through Activation of the p38 MAPK Pathway
Authors: Renukaradhya Gourapura J. , Khan Masood A. , Shaji Daniel , Brutkiewicz Randy R.
Published: September 2008

Natural killer T (NKT) cells are unique T lymphocytes that recognize CD1d-bound lipid antigens and play an important role in both innate and acquired immune responses against infectious diseases and tumors. We have already shown that a vesicular stomatitis virus (VSV) infection results in the rapid inhibition of murine CD1d-mediated antigen presentation to NKT cells. In the present study, it was found that the VSV matrix (VSV-M) protein is an important element in this decrease in antigen presentation postinfection. The VSV-M protein altered the intracellular distribution of murine CD1d molecules, resulting in qualitative (but not quantitative) changes in cell surface CD1d expression. The M protein was distributed throughout the infected cell, and it was found to activate the mitogen-activated protein kinase (MAPK) p38 very early postinfection. Infection of CD1d+cells with a temperature-sensitive VSV-M mutant at the nonpermissive temperature both substantially reversed the inhibition of antigen presentation by CD1d and delayed the activation of p38. Thus, the VSV-M protein plays an important role in permitting the virus to evade important components of the innate immune response by regulating specific MAPK pathways.
Escape from HLA-B*08-Restricted CD8 T Cells by Hepatitis C Virus Is Associated with Fitness Costs
Authors: Salloum Shadi , Oniangue-Ndza Cesar , Neumann-Haefelin Christoph , Hudson Laura , Giugliano Silvia , aus dem Siepen Marc , Nattermann Jacob , Spengler Ulrich , Lauer Georg M. , Wiese Manfred , Klenerman Paul , Bright Helen , Scherbaum Norbert , Thimme Robert , Roggendorf Michael , Viazov Sergei , Timm Joerg
Published: September 2008

The inherent sequence diversity of the hepatitis C virus (HCV) represents a major hurdle for the adaptive immune system to control viral replication. Mutational escape within targeted CD8 epitopes during acute HCV infection has been well documented and is one possible mechanism for T-cell failure. HLA-B*08 was recently identified as one HLA class I allele associated with spontaneous clearance of HCV replication. Selection of escape mutations in the immunodominant HLA-B*08-restricted epitope HSKKKCDEL
1395-1403
was observed during acute infection. However, little is known about the impact of escape mutations in this epitope on viral replication capacity. Their previously reported reversion back toward the consensus residue in patients who do not possess the B*08 allele suggests that the consensus sequence in this epitope is advantageous for viral replication in the absence of immune pressure. The aim of this study was to determine the impact of mutational escape from this immunodominant epitope on viral replication. We analyzed it with a patient cohort with chronic HCV genotype 1b infection and in a single-source outbreak (genotype 1b). Sequence changes in this highly conserved region are rare and selected almost exclusively in the presence of the HLA-B*08 allele. When tested in the subgenomic replicon (Con1), the observed mutations reduce viral replication compared with the prototype sequence. The results provide direct evidence that escape mutations in this epitope are associated with fitness costs and that the antiviral effect of HLA-B*08-restricted T cells is sufficiently strong to force the virus to adopt a relatively unfavorable sequence.
Epstein-Barr Virus BGLF4 Kinase Induces Disassembly of the Nuclear Lamina To Facilitate Virion Production
Authors: Lee Chung-Pei , Huang Yu-Hao , Lin Su-Fang , Chang Yao , Chang Yu-Hsin , Takada Kenzo , Chen Mei-Ru
Published: September 2008

DNA viruses adopt various strategies to modulate the cellular environment for efficient genome replication and virion production. Previously, we demonstrated that the BGLF4 kinase of Epstein-Barr virus (EBV) induces premature chromosome condensation through the activation of condensin and topoisomerase IIα (C. P. Lee, J. Y. Chen, J. T. Wang, K. Kimura, A. Takemoto, C. C. Lu, and M. R. Chen, J. Virol. 81:5166-5180, 2007). In this study, we show that BGLF4 interacts with lamin A/C and phosphorylates lamin A protein in vitro. Using a green fluorescent protein (GFP)-lamin A system, we found that Ser-22, Ser-390, and Ser-392 of lamin A are important for the BGLF4-induced disassembly of the nuclear lamina and the EBV reactivation-mediated redistribution of nuclear lamin. Virion production and protein levels of two EBV primary envelope proteins, BFRF1 and BFLF2, were reduced significantly by the expression of GFP-lamin A(5A), which has five Ser residues replaced by Ala at amino acids 22, 390, 392, 652, and 657 of lamin A. Our data indicate that BGLF4 kinase phosphorylates lamin A/C to promote the reorganization of the nuclear lamina, which then may facilitate the interaction of BFRF1 and BFLF2s and subsequent virion maturation. UL kinases of alpha- and betaherpesviruses also induce the disassembly of the nuclear lamina through similar sites on lamin A/C, suggesting a conserved mechanism for the nuclear egress of herpesviruses.
Evolution of CCR5 Use before and during Coreceptor Switching
Authors: Coetzer Mia , Nedellec Rebecca , Salkowitz Janelle , McLaughlin Sherry , Liu Yi , Heath Laura , Mullins James I. , Mosier Donald E.
Published: September 2008

The envelope gene (
env
) of human immunodeficiency virus type 1 (HIV-1) undergoes rapid divergence from the transmitted sequence and increasing diversification during the prolonged course of chronic infection in humans. In about half of infected individuals or more,
env
evolution leads to expansion of the use of entry coreceptor from CCR5 alone to CCR5 and CXCR4. The stochastic nature of this coreceptor switch is not well explained by host selective forces that should be relatively constant between infected individuals. Moreover, differences in the incidence of coreceptor switching among different HIV-1 subtypes suggest that properties of the evolving virus population drive the switch. We evaluated the functional properties of sequential
env
clones from a patient with evidence of coreceptor switching at 5.67 years of infection. We found an abrupt decline in the ability of viruses to use CCR5 for entry at this time, manifested by a 1- to 2-log increase in susceptibility to CCR5 inhibitors and a reduced ability to infect cell lines with low CCR5 expression. There was an abnormally rapid 5.4% divergence in
env
sequences from 4.10 to 5.76 years of infection, with the V3 and V4/V5 regions showing the greatest divergence and evidence of positive selection. These observations suggest that a decline in the fitness of R5 virus populations may be one driving force that permits the emergence of R5X4 variants.
Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement
Authors: Xu Zhili , Tian Jie , Smith Jeffrey S. , Byrnes Andrew P.
Published: September 2008

Kupffer cells (KCs) rapidly remove intravenously injected adenovirus (Ad) vectors from the circulation. A better understanding of the mechanisms involved could suggest strategies to improve Ad gene delivery by suppressing or evading KC uptake. We recently showed that clearance of Ad type 5 vectors by KCs does not involve the interaction of Ad with the well-established Ad receptors, namely, integrins or the coxsackievirus and Ad receptor (J. S. Smith, Z. Xu, J. Tian, S. C. Stevenson, and A. P. Byrnes, Hum. Gene Ther. 19:547-554, 2008). In the current study, we systematically quantified the contributions of various receptors and plasma proteins to the clearance of Ad by KCs. We found that scavenger receptors are a predominant mechanism for the clearance of Ad by KCs. In addition, we found that Ad is opsonized by natural immunoglobulin M antibodies and complement and that these opsonins play a contributory role in the clearance of Ad by KCs. We also examined additional mechanisms that have been postulated to be involved in the clearance of Ad, including the binding of Ad to platelets and vitamin K-dependent coagulation factors, but we found that neither of these were required for the clearance of Ad by KCs.
Compatibility among Polymerase Subunit Proteins Is a Restricting Factor in Reassortment between Equine H7N7 and Human H3N2 Influenza Viruses
Authors: Li Chengjun , Hatta Masato , Watanabe Shinji , Neumann Gabriele , Kawaoka Yoshihiro
Published: September 2008

Reassortment is an important driving force for influenza virus evolution, and a better understanding of the factors that affect this process could improve our ability to respond to future influenza pandemics and epidemics. To identify factors that restrict the generation of reassortant viruses, we cotransfected human embryonic kidney cells with plasmids for the synthesis of viral RNAs of both A/equine/Prague/1/56 (Prague; H7N7) and A/Yokohama/2017/03 (Yokohama; H3N2) viruses together with the supporting protein expression plasmids. Of the possible 256 genotypes, we identified 29 genotypes in 120 randomly plaque-picked reassortants examined. Analyses of these reassortants suggested that the formation of functional ribonucleoprotein (RNP) complexes was a restricting factor, a finding that correlated with the activities of RNP complexes composed of different combinations of the proteins from the two viruses, as measured in a minigenome assay. For at least one nonfunctional RNP complex (i.e., Prague PB2, Prague PB1, Yokohama PA, and Prague NP), the lack of activity was due to the inability of the three polymerase subunit proteins to form a heterotrimer. Adaptation of viruses possessing a gene encoding a chimera of the PA proteins of the two viruses and the remaining genes from Prague virus resulted in compensatory mutations in the PB2 and/or PA protein. These results indicate substantial incompatibility among the gene products of the two test viruses, a critical role for the RNP complex in the generation of reassortant viruses, and a functional interaction of PB2 and PA.
The Immune Evasion Paradox: Immunoevasins of Murine Cytomegalovirus Enhance Priming of CD8 T Cells by Preventing Negative Feedback Regulation
Authors: Böhm Verena , Simon Christian O. , Podlech Jürgen , Seckert Christof K. , Gendig Dorothea , Deegen Petra , Gillert-Marien Dorothea , Lemmermann Niels A. W. , Holtappels Rafaela , Reddehase Matthias J.
Published: September 2008

Cytomegaloviruses express glycoproteins that interfere with antigen presentation to CD8 T cells. Although the molecular modes of action of these “immunoevasins” differ between cytomegalovirus species, the convergent biological outcome is an inhibition of the recognition of infected cells. In murine cytomegalovirus, m152/gp40 retains peptide-loaded major histocompatibility complex class I molecules in acis-Golgi compartment, m06/gp48 mediates their vesicular sorting for lysosomal degradation, and m04/gp34, although not an immunoevasin in its own right, appears to assist in the concerted action of all three molecules. Using the Ld-restricted IE1 epitope YPHFMPTNL in the BALB/c mouse model as a paradigm, we provide here an explanation for the paradox that immunoevasins enhance CD8 T-cell priming although they inhibit peptide presentation in infected cells. Adaptive immune responses are initiated in the regional lymph node (RLN) draining the site of pathogen exposure. In particular for antigens that are not virion components, the magnitude of viral gene expression providing the antigens is likely a critical parameter in priming efficacy. We have therefore focused on the events in the RLN and have related priming to intranodal viral gene expression. We show that immunoevasins enhance priming by downmodulating an early CD8 T-cell-mediated “negative feedback” control of the infection in the cortical region of the RLN, thus supporting the model that immunoevasins improve antigen supply for indirect priming by uninfected antigen-presenting cells. As an important consequence, these findings predict that deletion of immunoevasin genes in a replicative vaccine virus is not a favorable option but may, rather, be counterproductive.
Human Cytomegalovirus Glycoproteins gB and gH/gL Mediate Epithelial Cell-Cell Fusion When Expressed either in
cis
or in
trans
Authors: Vanarsdall Adam L. , Ryckman Brent J. , Chase Marie C. , Johnson David C.
Published: September 2008

Herpesviruses use a cascade of interactions with different cell surface molecules to gain entry into cells. In many cases, this involves binding to abundant glycosaminoglycans or integrins followed by interactions with more limited cell surface proteins, leading to fusion with cellular membranes. Human cytomegalovirus (HCMV) has the ability to infect a wide variety of human cell types in vivo. However, very little is known about which HCMV glycoproteins mediate entry into various cell types, including relevant epithelial and endothelial cells. For other herpesviruses, studies of cell-cell fusion induced by viral proteins have provided substantial information about late stages of entry. In this report, we describe the fusion of epithelial, endothelial, microglial, and fibroblast cells in which HCMV gB and gH/gL were expressed from nonreplicating adenovirus vectors. Fusion frequently involved the majority of cells, and gB and gH/gL were both necessary and sufficient for fusion, whereas no fusion occurred when either glycoprotein was omitted. Coexpression of UL128, UL130, and UL131 did not enhance fusion. We concluded that the HCMV core fusion machinery consists of gB and gH/gL. Coimmunoprecipitation indicated that HCMV gB and gH/gL can interact. Importantly, expression of gB and gH/gL in
trans
(gB-expressing cells mixed with other gH/gL-expressing cells) resulted in substantial fusion. We believe that this is the first description of a multicomponent viral fusion machine that can be split between cells. If gB and gH/gL must interact for fusion, then these molecules must reach across the space between apposing cells. Expression of gB and gH/gL in
trans
with different cell types revealed surface molecules that are required for fusion on HCMV-permissive cells but not on nonpermissive cells.
Mutational Analysis of
cis
-Acting RNA Signals in Segment 7 of Influenza A Virus
Authors: Hutchinson Edward C. , Curran Martin D. , Read Eliot K. , Gog Julia R. , Digard Paul
Published: September 2008

The genomic viral RNA (vRNA) segments of influenza A virus contain specific packaging signals at their termini that overlap the coding regions. To further characterize
cis
-acting signals in segment 7, we introduced synonymous mutations into the terminal coding regions. Mutation of codons that are normally highly conserved reduced virus growth in embryonated eggs and MDCK cells between 10- and 1,000-fold compared to that of the wild-type virus, whereas similar alterations to nonconserved codons had little effect. In all cases, the growth-impaired viruses showed defects in virion assembly and genome packaging. In eggs, nearly normal numbers of virus particles that in aggregate contained apparently equimolar quantities of the eight segments were formed, but with about fourfold less overall vRNA content than wild-type virions, suggesting that, on average, fewer than eight segments per particle were packaged. Concomitantly, the particle/PFU and segment/PFU ratios of the mutant viruses showed relative increases of up to 300-fold, with the behavior of the most defective viruses approaching that predicted for random segment packaging. Fluorescent staining of infected cells for the nucleoprotein and specific vRNAs confirmed that most mutant virus particles did not contain a full genome complement. The specific infectivity of the mutant viruses produced by MDCK cells was also reduced, but in this system, the mutations also dramatically reduced virion production. Overall, we conclude that segment 7 plays a key role in the influenza A virus genome packaging process, since mutation of as few as 4 nucleotides can dramatically inhibit infectious virus production through disruption of vRNA packaging.
Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C
Authors: Binley James M. , Lybarger Elizabeth A. , Crooks Emma T. , Seaman Michael S. , Gray Elin , Davis Katie L. , Decker Julie M. , Wycuff Diane , Harris Linda , Hawkins Natalie , Wood Blake , Nathe Cory , Richman Douglas , Tomaras Georgia D. , Bibollet-Ruche Frederic , Robinson James E. , Morris Lynn , Shaw George M. , Montefiori David C. , Mascola John R.
Published: September 2008

Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date.
UNESCO Global Ethics Observatory: database on ethics related legislation and guidelines
Authors: Ang T W , Have H ten , Solbakk J H , Nys H
Published: September 2008

The Database on Ethics Related Legislation and Guidelines was launched in March 2007 as the fourth database of the UNESCO Global Ethics Observatory system of databases in ethics of science and technology. The database offers a collection of legal instruments searchable by region, country, bioethical themes, legal categories and applicability to specific articles of the UNESCO Universal Declaration on Bioethics and Human Rights and International Declaration on Human Genetic Data. This paper discusses the background and rationale for the database and its role as a consultative and comparative resource hub for the study of ethics related legal instruments across the world, with the purpose of informing and inspiring relevant stakeholders on the implementation of the principles contained within the UNESCO declarations on bioethics.
Signed, sealed and delivered: “big tobacco” in Hollywood, 1927–1951
Authors: Lum K L , Polansky J R , Jackler R K , Glantz S A
Published: September 2008

Objective:

Smoking in movies is associated with adolescent and young adult smoking initiation. Public health efforts to eliminate smoking from films accessible to youth have been countered by defenders of the status quo, who associate tobacco imagery in “classic” movies with artistry and nostalgia. The present work explores the mutually beneficial commercial collaborations between the tobacco companies and major motion picture studios from the late 1920s through the 1940s.

Methods:

Cigarette endorsement contracts with Hollywood stars and movie studios were obtained from internal tobacco industry documents at the University of California, San Francisco (UCSF) Legacy Tobacco Documents Library and the Jackler advertising collection at Stanford.

Results:

Cigarette advertising campaigns that included Hollywood endorsements appeared from 1927 to 1951, with major activity in 1931–2 and 1937–8 for American Tobacco Company’s Lucky Strike, and in the late 1940s for Liggett & Myers’ Chesterfield. Endorsement contracts and communication between American Tobacco and movie stars and studios explicitly reveal the cross-promotional value of the campaigns. American Tobacco paid movie stars who endorsed Lucky Strike cigarettes US$218 750 in 1937–8 (equivalent to US$3.2 million in 2008) for their testimonials.

Conclusions:

Hollywood endorsements in cigarette advertising afforded motion picture studios nationwide publicity supported by the tobacco industry’s multimillion US dollar advertising budgets. Cross-promotion was the incentive that led to a synergistic relationship between the US tobacco and motion picture industries, whose artefacts, including “classic” films with smoking and glamorous publicity images with cigarettes, continue to perpetuate public tolerance of onscreen smoking. Market-based disincentives within the film industry may be a solution to decouple the historical association between Hollywood films and cigarettes.
Fungi associated with Tomicus minor on Pinus sylvestris in Poland and their succession into the sapwood of beetle-infested windblown trees
Authors: Jankowiak Robert
Published: September 2008

The study identified and measured frequency of fungal species associated with Tomicus minor (Hart.) on Pinus sylvestris L. (Scots pine) in Poland. Additionally, fungal succession in P. sylvestris sapwood was investigated during a 12 week period following an attack by this insect. Fungi were isolated from five populations of overwintered adult beetles and their galleries with 59 species of fungi being represented among the 2880 cultures obtained. The most frequent species, Ophiostoma canum (Münch) Syd. & P. Syd., Hormonema dematioides Lagerb. & Melin, and Ambrosiella tingens (Lagerb. & Melin) L.R. Batra, appeared to be specifically associated with T. minor. The succesional changes in species composition during a 12 week period following an attack by T. minor were observed. The pattern of fungal succession in P. sylvestris sapwood essentially agreed with a general scheme of fungal succession in tree sapwood infested by bark beetles. Ambrosiella tingens was the first invader of sapwood and occurred most frequently in its deeper layers. Ophiostoma canum, H. dematioides, and other molds were also often isolated from the sapwood; however, they were most common at a depth of 5 mm during the initial phase of fungal colonization. Later, Ophiostoma canum followed A. tingens in the sapwood invasion.
Resistance of Pinus taeda families under artificial inoculations with diverse fusiform rust pathogen populations and comparison with field trials
Authors: Isik Fikret , Amerson Henry V. , Whetten Ross W. , Garcia Saul A. , Li Bailian , McKeand Steven E.
Published: September 2008

Controlled inoculations with 10 bulk inocula of Cronartium quercuum (Berk) Miyabe ex Shirai f.sp. fusiforme were carried out on open-pollinated progeny of 25 fast-growing Pinus taeda L. parents. The parents had a range of breeding values for resistance to fusiform rust in progeny field trials. There were highly significant differences among the half-sib families in response to inoculations, and these differences were very reproducible; the half-sib family-mean heritability of resistance to controlled inoculation was 0.97. All of the families that were susceptible in the field were susceptible in controlled inoculations, and most (12 of 17) of the field-resistant families were resistant in response to controlled inoculations. Significant pathogenic variability was observed among the different bulk inocula, although this accounted for only 1.9% of the total variation. Genetic differences among families within field-resistant or field-susceptible groups accounted for 13.7% of the total variation. The family by inocula interaction was highly significant, but a single field-resistant family contributed 44% of the total family by inocula interaction variance, and two other field-resistant families also showed significant interactions.
ON THE ASPHERICITY OF CERTAIN RELATIVE PRESENTATIONS OVER TORSION-FREE GROUPS
Authors: KIM SEONG KUN
Published: September 2008

It is noteworthy to find whether a relative presentation with torsion-free coefficients is aspherical or not, since a nonaspherical relative presentation that defines a torsion-free group would provide a potential counterexample to the Kaplansky zero-divisor conjecture, see [7]. In this paper we investigate asphericity of the relative group presentation [Formula: see text] provided that m1, m2, …, mk are nonzero integers, k ≤ 3, each coefficient has infinite order and the relator is not a proper power.
SMALL p-GROUPS WITH FULL-RANK FACTORIZATION
Authors: HAANPÄÄ HARRI , ÖSTERGÅRD PATRIC R. J. , SZABÓ SÁNDOR
Published: September 2008

The problem of determining which abelian groups admit a full-rank normalized factorization is settled for the orders 64 = 26, 81 = 34, and 128 = 27. By a computer-aided approach, it is shown that such groups of these orders are exactly those of type (22,22,22), (22,22,2,2), (23,22,22), (23,22,2,2), (22,22,22,2), and (22,22,2,2,2).
SCHUR MULTIPLIERS OF n-ENGEL GROUPS
Authors: MORAVEC PRIMOŽ
Published: September 2008

We find a bound for the exponent of the Schur multiplier of a finite p-group in terms of the exponent and Engel length of the given group. It is also proved that if G is a 3-Engel group of finite exponent, then the exponent of H2(G) divides exp G. When G is a 4-Engel group of exponent e, the exponent of H2(G) divides 10e.
READING OFF KUROSH DECOMPOSITIONS
Authors: MARKUS-EPSTEIN L.
Published: September 2008

Geometric methods proposed by Stallings for treating finitely generated subgroups of free groups were successfully used to solve a wide collection of decision problems for free groups and their subgroups.

In the present paper we employ the generalized Stallings' folding method, developed by the author, to introduce a procedure, which has given a subgroup H of a free product of finite groups reads off its Kurosh decomposition from the subgroup graph of H.
CORRIGENDUM: "MINIMAL SEMIGROUPS GENERATING VARIETIES WITH COMPLEX SUBVARIETY LATTICES"
Authors: LEE EDMOND W. H.
Published: September 2008

A gap in the proof of Proposition 4.5 in the article cited in the heading is mended.
ORDERINGS ON ARTIN–TITS GROUPS
Authors: SIBERT HERVE
Published: September 2008

We prove that a construction similar to that described by Dehornoy in the case of braids is possible for every Artin–Tits group, yielding a partial ordering. A necessary condition for this partial order to be linear is that the associated Coxeter graph consists only of disjoint lines. So, in particular, type D is dismissed.
MODELING OF KNEE ARTICULAR CARTILAGE DISSIPATION DURING GAIT ANALYSIS
Authors: DESMARAIS MATHIEU , AISSAOUI RACHID
Published: September 2008

Articular cartilage dissipates contact loads according to three dissipative mechanisms: frictional drag, intrinsic viscoelasticity, and surface friction. Estimation of dissipation due to these three mechanisms during gait is required to understand the dissipative properties of articular cartilage. Fourteen healthy subjects performed a gait analysis on treadmill. Tibiofemoral contact forces were estimated from inverse dynamic analysis and from a reductionist knee contact model. These contact forces and the results obtained from a preloading creep simulation were introduced into a biphasic poroviscoelastic articular cartilage model, and a one-dimensional confined compression was performed. Articular dissipation from each dissipative mechanism was estimated. Sensitivity analysis was performed to determine the effects of material parameters and length of the preloading simulation on the patterns of the dissipative mechanisms. Dissipative force patterns for all dissipative mechanisms were found to be similar to those of tibiofemoral contact forces. Frictional drag was found to be the dominant dissipative mechanism. The initial permeability and the viscoelastic spectrum parameters were found to have an important impact on the magnitude of the peaks of dissipative patterns. If appropriate material parameters are introduced, this model could be used to compare the difference between healthy and osteoarthritic human articular cartilage.
SEGMENT CLASSIFICATION OF ECG DATA AND CONSTRUCTION OF SCATTER PLOTS USING PRINCIPAL COMPONENT ANALYSIS
Authors: CHAWLA M. P. S.
Published: September 2008

In many medical applications, feature selection is obvious; but in medical domains, selecting features and creating a feature vector may require more effort. The wavelet transform (WT) technique is used to identify the characteristic points of an electrocardiogram (ECG) signal with fairly good accuracy, even in the presence of severe high-frequency and low-frequency noise. Principal component analysis (PCA) is a suitable technique for ECG data analysis, feature extraction, and image processing — an important technique that is not based upon a probability model. The aim of the paper is to derive better diagnostic parameters for reducing the size of ECG data while preserving morphology, which can be done by PCA. In this analysis, PCA is used for decorrelation of ECG signals, noise, and artifacts from various raw ECG data sets. The aim of this paper is twofold: first, to describe an elegant algorithm that uses WT alone to identify the characteristic points of an ECG signal; and second, to use a composite WT-based PCA method for redundant data reduction and better feature extraction. PCA scatter plots can be observed as a good basis for feature selection to account for cardiac abnormalities. The study is analyzed with higher-order statistics, in contrast to the conventional methods that use only geometric characteristics of feature waves and lower-order statistics. A new algorithm — viz. PCA variance estimator — is developed for this analysis, and the results are also obtained for different combinations of leads to find correlations for feature classification and useful diagnostic information. PCA scatter plots of various chest and augmented ECG leads are obtained to examine the varying orientations of the ECG data in different quadrants, indicating the cardiac events and abnormalities. The efficacy of the PCA algorithm is tested on different leads of 12-channel ECG data; file no. 01 of the Common Standards for Electrocardiography (CSE) database is used for this study. Better feature extraction is obtained for some specific combinations of leads, and significant improvement in signal quality is achieved by identifying the noise and artifact components. The quadrant analysis discussed in this paper highlights the filtering requirements for further ECG processing after performing PCA, as a primary step for decorrelation and dimensionality reduction. The values of the parameters obtained from the results of PCA are also compared with those of wavelet methods.
ANTICYTOSKELETAL DRUGS AND TIME CULTURE EFFECTS UPON THE MECHANICAL BEHAVIOR OF DERMAL EQUIVALENT TISSUE SUBMITTED TO UNCONFINED COMPRESSION LOADING
Authors: RAMTANI S. , GEIGER D.
Published: September 2008

The dermal equivalent (DE), a dermis substitute consisting of human skin fibroblasts growing into a three-dimensional collagen matrix, is extensively used in many applications: wound-healing response, pharmacological studies, skin grafting, fibroblast proliferation and migration, extracellular matrix remodeling, and efficacy of cosmetic products. The widespread growth of numerical modeling in biomechanical research has placed a heightened emphasis on accurate material property data for soft biological tissues, in particular for equivalent dermis which has not been so thoroughly investigated. Under unconfined compression loading, the effects of the strain rate, time culture, and cytoskeleton-disrupting agents are experimentally investigated. In order to model the observed mechanical behavior of the DE under the above conditions, the internal state variable approach is adopted for finite deformation viscoelasticity and the optimized material parameters are identified with respect to the stated thermodynamic restriction (i.e. positive viscous dissipation).
USER-PRODUCER INTERACTIONS IN EMERGING PHARMACEUTICAL AND FOOD INNOVATIONS
Authors: MOORS E. H. M. , BOON W. P. C. , NAHUIS R. , VANDEBERG R. L. J.
Published: September 2008

In order to study user-producer interaction (UPI) in emerging pharmaceutical and food innovation processes, a classification of user involvement has been developed, including a contextualised view on UPIs. Case studies are performed on two types of UPI: demand articulation in intermediary organisations and interactive learning in consortia, in the pharmaceutical and food sector, respectively.

Regarding demand articulation processes, articulation of problems, needs, demands and expectations through agenda-setting practices is important. Expression and evaluation of demands with other factors leads to moblization of creative potential of prospective users and facilitation of emerging innovation processes.

Regarding interactive learning, geographical, organisational, regulatory and cognitive proximity conditions could facilitate structures for emerging technology development, and codes and networks for frequent interaction between complementary stakeholders. Demands, concerns and opportunities are articulated by shared visions. Organised UPIs via intermediary user organisations or consortia seem to be the important tools for demand articulation and interactive learning involving patient organisations, researchers and private and public organisations.
TRANSITION PATHWAYS TOWARDS USER-CENTRIC INNOVATION
Authors: WARNKE PHILINE , WEBER MATTHIAS , LEITNER KARL-HEINZ
Published: September 2008

Although various user-centric innovation concepts have proved successful in niche markets and specific industries, there is yet little understanding how these models may become more widely diffused in manufacturing industries. We apply an evolutionary economics perspective to explore possible transition pathways towards user-centric innovation paradigms. In order to understand not only the past but also possible future transition trajectories, we complement the co-evolution analysis with prospective elements such as scenario building and roadmapping. Using this combined approach, we identify possible future working configurations of user-centric innovation models and specify a number of diverse elements relevant on different levels of the transition arena. We argue that these insights can be used to define and set-up dedicated learning spaces for user-centric innovation. It is suggested that similar approaches may be useful for companies and policy actors to guide governance of change towards user-centric innovation models.
THE ROLE OF ONLINE BRAND COMMUNITY IN NEW PRODUCT DEVELOPMENT: CASE STUDIES ON DIGITAL PRODUCT MANUFACTURERS IN KOREA
Authors: KIM JOONG HYUN , BAE ZONG-TAE , KANG SHIN HYUNG
Published: September 2008

The focus of this study is on how online brand communities are utilised throughout the new product development (NPD) process by promoting communications between firms and communities. We investigate leading MP3 player manufacturers and mobile phone handset manufacturers in Korea. The results of our case studies show that the roles of online brand communities vary along the NPD stages — from trendsetters (lead users) to innovation facilitators (users as innovators), and information disseminators (early adopters). These communities can help firms gain insight into customer needs, desirable characteristics of new products and trends for future development. Furthermore, various inputs from online brand communities can stimulate firms' internal communication among several departments involved in the NPD. Finally, this study suggests the extended research model and generates hypotheses on the roles and impacts of online brand communities.
THREE APPROACHES TO TAKE THE USER PERSPECTIVE INTO ACCOUNT DURING NEW PRODUCT DESIGN
Authors: PALS NICO , STEEN MARC G. D. , LANGLEY DAVID J. , KORT JOKE
Published: September 2008

This paper addresses three different approaches which can be employed to adequately answer different questions faced by product developers. These approaches differ in the ways users themselves are involved in developing the "real" user perspective. In participatory design, products and product concepts are developed together with users so that they fit better with what the users do and want to do. The modelling of product adoption quantifies the likely market adoption of products, based on user characteristics and product attributes. The evaluation of user experience describes a way to evaluate products in terms of their users' interaction with the product daily life. These approaches have originated from different areas and are often seen as competing viewpoints. This paper shows that the three approaches be seen as complementary to each other and suggests a method for to choose the right approach.
INTERMEDIARIES, USERS AND SOCIAL LEARNING IN TECHNOLOGICAL INNOVATION
Authors: STEWART JAMES , HYYSALO SAMPSA
Published: September 2008

This paper explores the role of intermediaries in the development and appropriation of new technologies. We focus on intermediaries that facilitate user innovation, and the linking of user innovation into supply side activities. We review findings on intermediaries in some of our studies and other available literature to build a framework to explore of how intermediaries work in making innovation happen. We make sense of these processes by taking a long-term view of the dynamics of technology and market development using the social learning in technological innovation (SLTI) framework. Our primary concern is with innovation intermediaries and their core roles of configuring, facilitating and brokering technologies, uses and relationships in uncertain and emerging markets. We show the range of positions and influence they have along the supply-use axis in a number of different innovation contexts, and how they are able to bridge the user-developer innovation domains. Equipped with these insights, we explore in more depth how intermediaries affect the shape of new information and communication technologies and the importance of identifying and nurturing the user-side intermediaries that are crucial to innovation success.
PROACTIVE INVOLVEMENT OF CONSUMERS IN INNOVATION: SELECTING APPROPRIATE TECHNIQUES
Authors: JANSSEN KAREN L. , DANKBAAR BEN
Published: September 2008

There are many techniques for the involvement of consumers to support the development of innovations, but knowledge is lacking in the appropriateness of different techniques in various situations. This is, especially, true for consumer involvement in radical innovation. This paper presents the requirements of consumer involvement in different situations, covering the two main phases of the development process, and specified for three types of radical product innovation. Based on a review of literature, we identified four characteristics of consumers-involvement techniques and developed a mix of differentiating characteristics for six situations in the new product development, which form the basis of a model to select the appropriate techniques. We then evaluated this model by using a historical comparative case-study approach. This paper contributes to the understanding of the appropriateness of different techniques for the proactive involvement of consumers to support the development of radical product innovations.
THE FREEDOM-FIGHTERS: HOW INCUMBENT CORPORATIONS ARE ATTEMPTING TO CONTROL USER-INNOVATION
Authors: BRAUN VIKTOR , HERSTATT CORNELIUS
Published: September 2008

Novel information and communication technologies, foremost the Internet, have revolutionised the innovation landscape. Mass-collaboration involving end-users is now, a critical component of many types of software improvement and has the potential to make users as the main innovation source of the 21st century. The vision of democratising innovation is not, however, in everybody's interest. Many incumbent corporations are actively engaging in efforts to prevent users from modifying and improving their products. In this paper, we investigate the barriers that incumbents impose upon potentially innovative users and ask under which conditions such behaviours are likely to be sustainable.
THE DYNAMICS OF USER INNOVATION: DRIVERS AND IMPEDIMENTS OF INNOVATION ACTIVITIES
Authors: RAASCH CHRISTINA , HERSTATT CORNELIUS , LOCK PHILLIP
Published: September 2008

Users have proven to be a principal driving force of many innovations in different industries. Therefore, more and more firms try to identify avenues to systematically involve users into their new product development. Despite the growing interest in user-driven or user-centred innovation, both in academia and industry, the drivers and impediments affecting the evolvement of user innovation activities over time have only recently become a focus of analysis. This study aims to examine user innovation over time and contribute to the extension of the existing model of user-driven innovation to a more dynamic setting. For this purpose, we study the evolution of user innovation in a field of sports equipment, a high-performance sailboat called Moth. We analyse innovation activities over several decades based on secondary data, interviews and survey results. We find that the level of user activity does not follow a unidirectional trend, but rather develops depending on a number of contextual factors. This suggests that, given a stimulating setting, user innovation can be sustained over long periods of time.
USER-CENTRED IMPROVEMENTS TO ENERGY EFFICIENCY PRODUCTS AND RENEWABLE ENERGY SYSTEMS: RESEARCH ON HOUSEHOLD ADOPTION AND USE
Authors: CAIRD SALLY , ROY ROBIN
Published: September 2008

The development and rapid consumer adoption of energy efficiency products and renewable energy systems are key elements of the UK and the EU carbon reduction strategies to meet the challenge of climate change. Many such technologies are available for domestic use, but despite government incentives to meet carbon reduction targets consumer adoption has been slow. This Open University research with 111 in-depth interviews plus an on-line survey with nearly 400 responses, investigates consumer adoption, non-adoption and use of these technologies. Results show that it is important to research consumer use experiences, problems and requirements when designing and developing "green" technologies. With results tailored to each technology, this study shows that user-centred improvements are required to improve functionality, ergonomics, inter-connectedness with other systems and symbolic value, and to reduce cost and payback. User-centred research supports new product/system design and development to promote more rapid adoption and carbon-saving use of energy efficient and renewable technologies in homes.
OUTLAW COMMUNITY INNOVATIONS
Authors: SCHULZ CELINE , WAGNER STEFAN
Published: September 2008

Recent studies of outlaw communities provide qualitative evidence of their existence and the organisation of the underlying innovation processes. We provide descriptive results from a large scale survey of two online outlaw communities focussing on Microsoft's XBox (a gaming console). Based on the previous findings, we identify two types of participants in outlaw communities — user innovators and adopters. Based on 2256 responses, we find that users modify their XBox mainly to be able to increase the set of available functions of their XBox. Users are also motivated to modify their XBox for the sake of having fun and to conduct pirate behaviour. Finally, results from our survey also suggest that user innovators are largely intrinsically motivated by fun and the intellectual stimulation of writing code for homebrew software.
Conflict, Convergent Evolution, and the Relative Importance of Immature and Adult Characters in Endopterygote Phylogenetics
Authors: Meier Rudolf , Lim Gwynne Shimin
Published: September 2008

We use two episodes from systematic history to illustrate how conflict between immature and adult data was important for the development of phylogenetic systematics. A reference search in Zoological Record reveals that most phylogenetic analyses of endopterygote insects continue to utilize morphological rather than DNA sequence data. However, the use of immature and adult data is established for only a few taxa. An assessment of the phylogenetic utility of 73 matrices with immature and adult data reveals that the immature partitions have fewer characters and that immature characters provide lower node support through homoplasy levels in immatures, and adult partitions are comparable. Despite much conflict, analyses based on all available evidence yield better tree resolution and higher support. We argue that DNA sequence-based matching of immature and adult stages will greatly help with the study of endopterygote immatures and facilitate the assembly of combined character matrices with data from all life-history stages.
Host-Parasitoid Associations in Strepsiptera
Authors: Kathirithamby Jeyaraney
Published: September 2008

Strepsiptera are obligate endoparasitoids that exhibit extreme sexual dimorphism and parasitize seven orders and 33 families of Insecta. The adult males and the first instar larvae in the Mengenillidia and Stylopidia are free-living, whereas the adult females in Mengenillidia are free-living but in the suborder Stylopidia they remain endoparasitic in the host. Parasitism occurs at the host larval/nymphal stage and continues in a mobile host until that host's adult stage. The life of the host is lengthened to allow the male strepsipteran to complete maturation and the viviparous female to release the first instar larvae when the next generation of the host's larvae/nymphs has been produced. The ability of strepsipterans to parasitize a wide range of hosts, in spite of being endoparasitoids, is perhaps due to their unique immune avoidance system. Aspects of virulence, heterotrophic heteronomy in the family Myrmecolacidae, cryptic species, genomics, immune response, and behavior of stylopized hosts are discussed in this chapter.
Lagrangian Properties of Particles in Turbulence
Authors: Toschi Federico , Bodenschatz Eberhard
Published: September 2008

The Lagrangian description of turbulence is characterized by a unique conceptual simplicity and by an immediate connection with the physics of dispersion and mixing. In this article, we report some motivations behind the Lagrangian description of turbulence and focus on the statistical properties of particles when advected by fully developed turbulent flows. By means of a detailed comparison between experimental and numerical results, we review the physics of particle acceleration, Lagrangian velocity structure functions, and pairs and shapes evolution. Recent results for nonideal particles are discussed, providing an outlook on future directions.
Rheology of the Cytoskeleton
Authors: Mofrad Mohammad R.K.
Published: September 2008

The cytoskeleton is the primary internal structure of the cell, providing its structural integrity. The rheology and mechanics of the cytoskeleton, therefore, are key to the cell's ability to accomplish its diverse functions in health and disease. Although the importance of the cytoskeleton is well established, the relationship between the microstructural details and the macroscopic rheological behavior of the cytoskeleton remains elusive. A wide range of computational and phenomenological models as well as experimental techniques have been proposed over the past two decades to describe the cytoskeleton, giving rise to several, often contradictory, theories for describing its rheology. This concise review attempts to bring together the key experimental methods and theoretical and computational models regarding cytoskeletal rheology and mechanics.