bluuebunny/crossref_metadata_2025 huggingface dataset:
Large positive and negative lateral optical beam displacements due to surface plasmon resonance
Authors: Yin Xiaobo , Hesselink Lambertus , Liu Zhaowei , Fang Nicholas , Zhang Xiang
Published: July 2004

We report abnormally large positive and negative lateral optical beam shifts at a metal–air interface when the surface plasmon resonance of the metal is excited. The optimal thickness for minimal resonant reflection is identified as the critical thickness above which a negative beam displacement is observed. Experimental results show good agreement with theoretical predictions and the large observed bidirectional beam displacements also indicate the existence of forward and backward surface propagating waves at the surface plasmon resonance of the metal.
Isomer abundance of small carbon clusters formed in buffer He gas
Authors: Sheng Yang , Ning Xi-Jing , Li Peng
Published: July 2004

We calculated the isomer spectrum of carbon clusters of 3–36 atoms, and performed molecular dynamics simulations of the cluster growth in buffer helium gas, showing that the isomers with potentials higher than those of the most stable clusters form with considerable probabilities under common experimental conditions.
Older age becomes common late in human evolution
Authors: Caspari Rachel , Lee Sang-Hee
Published: July 2004

Increased longevity, expressed as number of individuals surviving to older adulthood, represents one of the ways the human life history pattern differs from other primates. We believe it is a critical demographic factor in the development of human culture. Here, we examine when changes in longevity occurred by assessing the ratio of older to younger adults in four hominid dental samples from successive time periods, and by determining the significance of differences in these ratios. Younger and older adult status is assessed by wear seriation of each sample. Whereas there is significant increased longevity between all groups, indicating a trend of increased adult survivorship over the course of human evolution, there is a dramatic increase in longevity in the modern humans of the Early Upper Paleolithic. We believe that this great increase contributed to population expansions and cultural innovations associated with modernity.
Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans
Authors: Davis Ian D. , Chen Weisan , Jackson Heather , Parente Phillip , Shackleton Mark , Hopkins Wendie , Chen Qiyuan , Dimopoulos Nektaria , Luke Tina , Murphy Roger , Scott Andrew M. , Maraskovsky Eugene , McArthur Grant , MacGregor Duncan , Sturrock Sue , Tai Tsin Yee , Green Simon , Cuthbertson Andrew , Maher Darryl , Miloradovic Lena , Mitchell Susan V. , Ritter Gerd , Jungbluth Achim A. , Chen Yao-Tseng , Gnjatic Sacha , Hoffman Eric W. , Old Lloyd J. , Cebon Jonathan S.
Published: July 2004

NY-ESO-1 is a “cancer-testis” antigen expressed in many cancers. ISCOMATRIX is a saponin-based adjuvant that induces antibody and T cell responses. We performed a placebo-controlled clinical trial evaluating the safety and immunogenicity of recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant. Forty-six evaluable patients with resected NY-ESO-1-positive tumors received three doses of vaccine intramuscularly at monthly intervals. The vaccine was well tolerated. We observed high-titer antibody responses, strong delayed-type hypersensitivity reactions, and circulating CD8+ and CD4+ T cells specific for a broad range of NY-ESO-1 epitopes, including known and previously unknown epitopes. In an unplanned analysis, vaccinated patients appeared to have superior clinical outcomes to those treated with placebo or protein alone. The vaccine is safe and highly potent immunologically.
Attenuation control of
pyrG
expression in
Bacillus subtilis
is mediated by CTP-sensitive reiterative transcription
Authors: Meng Qi , Turnbough Charles L. , Switzer Robert L.
Published: July 2004

In
Bacillus subtilis
and other Gram-positive bacteria, pyrimidine-mediated regulation of the
pyrG
gene, which encodes CTP synthetase, occurs through an attenuation mechanism involving an intrinsic transcription terminator in the
pyrG
leader region. Low intracellular levels of CTP prevent termination at the attenuator by a mechanism that requires the nontemplate strand sequence GGGC at the
pyrG
transcription initiation site (first G =+1) and the leader transcript sequence GCUCCC located at the 5′ end of the terminator RNA hairpin. In this study, we demonstrate that reiterative transcription adds G residues (up to at least 10) to the 5′ end of
pyrG
transcripts when
B
.
subtilis
cells are starved for pyrimidines but not when cells are grown with excess cytidine. Regulated repetitive addition of G residues, as well as pyrimidine-mediated
pyrG
regulation, requires the sequence GGGC or GGGT at the start of
pyrG
transcription. Mutational insertion of four extra G residues at the 5′ end of the
pyrG
transcript (i.e., 5′-GGGGGGGC) results in constitutive
pyrG
expression. We propose that the incorporation of extra G residues by reiterative transcription at the wild-type promoter occurs when normal transcription elongation is stalled at position +4 by low levels of the incoming substrate, CTP, during pyrimidine limitation. The poly(G) extensions on the 5′ ends of
pyrG
transcripts act to prevent transcription attenuation by base pairing with the sequence CUCCCUUUC located in the 5′ strand of the terminator hairpin. This control mechanism is likely to operate in other Gram-positive bacteria containing similar
pyrG
leader sequences.
The dynamics of genomic-length DNA molecules in 100-nm channels
Authors: Tegenfeldt Jonas O. , Prinz Christelle , Cao Han , Chou Steven , Reisner Walter W. , Riehn Robert , Wang Yan Mei , Cox Edward C. , Sturm James C. , Silberzan Pascal , Austin Robert H.
Published: July 2004

We show that genomic-length DNA molecules imaged in nanochannels have an extension along the channel that scales linearly with the contour length of the polymer, in agreement with the scaling arguments developed by de Gennes for self-avoiding confined polymers. This fundamental relationship allows us to measure directly the contour length of single DNA molecules confined in the channels, and the statistical analysis of the dynamics of the polymer in the nanochannel allows us to compute the SD of the mean of the extension. This statistical analysis allows us to measure the extension of λ DNA multimers with a 130-nm SD in 1 min.
Underreporting of energy intake from a self-administered food-frequency questionnaire completed by adults in Montreal
Authors: Bedard Daniel , Shatenstein Bryna , Nadon Sylvie
Published: July 2004

Background:

Energy intake determined from self-reported dietary assessment methods may be underreported. Therefore, it is important that such methods be validated against another with known validity for energy intake or energy expenditure.

Methods:

We investigated potential underestimation of energy intake obtained from our semi-quantitative food-frequency questionnaire (FFQ) administered between 2000 and 2001 in the metropolitan area of Montreal, Canada. The study population included 246 adults aged 18 to 82 years. The ratio of energy intake to estimated basal metabolic rate (EI/BMR) was used to assess underreporting and physical activity was determined from self-administered questions. Comparison of the EI/BMR ratio with the Goldberg statistical cut-off allowed us to detect individuals who were low energy reporters (LERs). LERs and non-LERs were compared to determine if they differed on sociodemographic, anthropometric and lifestyle variables.

Results:

The EI/BMR ratio was 1.26 for men and 1.32 for women. LERs represented 43% of the sample of individuals. Male LERs accounted for 54% compared with 35% among females. Underreporting of energy intake was highest in men and individuals who were older, heavier, with higher body mass index and lower education level. A higher proportion of male LERs perceived their financial situation as adequate while a greater proportion of female LERs considered themselves poor.

Conclusion:

Our data suggest that underreporting of energy intake from the FFQ was considerable and may bias dietary interpretation. As this was uneven across the sample, it is crucial to recognise the characteristics of LERs in order to increase the validity of reported energy intake.
Nine months postpartum weight retention predictors for Brazilian women
Authors: Kac Gilberto , Benicio Maria HDA , Velásquez-Meléndez Gustavo , Valente Joaquim G
Published: July 2004

Objective:

To identify factors potentially associated with weight retention measured 9 months after childbirth.

Design:

Prospective study with four follow-up waves in time (0.5, 2, 6 and 9 months postpartum).

Setting:

Rio de Janeiro, Brazil.

Subjects and methods:

Two hundred and sixty-six Brazilian women of childbearing age. Analysis was based on hierarchical logistic regression. The dependent variable was weight retention and was defined as the difference between weight at 9 months postpartum and pre-pregnancy weight, with a dichotomised cut-off at 7.5 kg. Covariates included demographic and socio-economic data, obstetric history, anthropometric data, and data on the infant. These data were grouped in blocks and ordered according to their influence on the dependent variable.

Results:

Of the women studied, 19.2% presented weight retention values ≥7.5 kg. According to the logistic regression analysis, the following variables remained associated with weight retention ≥7.5 kg: total family income, difficulty or inability to read a letter, age category ≥30 years, age at first childbirth <23 years, gestational weight gain ≥12 kg, body fat at baseline ≥30% and infant birth weight <3500 g. Infant hospitalisation was only marginally significant.

Conclusions:

Determinant factors identified by the analysis highlight the need for nutritional intervention policies during pregnancy and in the first months postpartum as a way of minimising obesity and the diseases resulting from it.
Waist circumference as a determinant of hypertension and diabetes in Brazilian women: a population-based study
Authors: Olinto MTA , Nacul LC , Gigante DP , Costa JSD , Menezes AMB , Macedo S
Published: July 2004

Objective:

To evaluate the role of central adiposity, as evaluated by the measurement of waist circumference (WC), as an independent risk factor for hypertension and type 2 diabetes mellitus in the setting of a developing country.

Design:

Population-based, cross-sectional study.

Setting:

A medium-sized town in southern Brazil.

Participants:

One thousand and ninety-five non-pregnant women, 20 to 69 years old, recruited by cluster random sampling between 1999 and 2000. Their mean WC was 85.3 cm (standard deviation 13.9 cm) and 23.3% (n = 255) were obese (body mass index >30 kg m−2). The prevalence of hypertension and diabetes was 25.6% (n = 280) and 6.2% (n = 68), respectively.

Results:

The risks of hypertension and diabetes were directly related to WC measurement. Women with WC > 80 cm had increased risk of hypertension (odds ratio (OR) = 6.2, P < 0.001). The association remained significant (OR = 1.04 per cm increase in WC, P = 0.02) after adjusting for confounders. The effect of WC on diabetes was modified by age. The effect was stronger in women younger than 40 years old (OR = 12.7, P = 0.016) than in those over 40 years old (OR = 2.8, P = 0.013). In the multivariate analysis, the odds ratio was 5.7 (P = 0.12) in those under 40 years old and 2.8 (P = 0.008) in older women.

Conclusions:

Waist circumference is an independent determinant for hypertension and diabetes in women in this population. The stronger association between WC and diabetes in younger women suggests that the validity of this indicator to assess abdominal adiposity is age-specific. Further studies should validate the usefulness of WC measurement in different age groups.
Applications of Magnetic Resonance Microscopy
Authors: Maronpot Robert R. , Sills Robert C. , Johnson G. Allan
Published: July 2004

Magnetic resonance imaging (MRI) has enjoyed enormous clinical success since the first demonstration of the method more than 30 years ago. An increasing number of pharmaceutical manufacturers seeking new biomarkers for assessing drug efficacy and toxicity are turning to MRI. A specific application of MRI promises to revolutionize pathology for the basic scientist in the same way MRI has forever altered the standard of care in the clinical domain. More specifically, this application is the use of magnetic resonance microscopy (MRM) in conjunction with new staining methodologies that now make MRM routinely available to the widest range of investigators.
Thresholds for the Effects of 2-Acetylaminofluorene in Rat Liver
Authors: Williams Gary M. , Iatropoulos Michael J. , Jeffrey Alan M.
Published: July 2004

To explore for practical thresholds for DNA-reactive carcinogens in rat liver carcinogenicity, we have conducted a series of exposure-response studies using 2 well-studied hepatocarcinogens, 2-acetylaminofluorene (AAF) and diethylnitrosamine (DEN). Findings with AAF, including as yet unpublished experiments, are reviewed here and related to DEN observations. In these studies, we have administered exact intragastric doses during an initiation segment (IS) of 12—16 weeks followed in some experiments by phenobarbital (PB) as a liver tumor promoter for 24 weeks to enhance manifestation of initiation. The cumulative doses (CD) of AAF at the end of ISs ranged from 0.094 to 282.2 mg/kg. Our findings for AAF in the IS can be summarized as follows: (1) the earliest parameter to be affected with administration of low doses was the appearance of DNA adducts (around 4 weeks), followed at higher doses by cell proliferation; (2) formation of DNA adducts was nonlinear, with a no-observed effect level (NOEL) at a CD of 0.094 mg/kg and a plateau at higher doses (94.1 mg/kg); (3) cytotoxicity (necrosis) showed a NOEL at a CD of 28.2 mg/kg; (4) compensatory hepatocellular proliferation showed a NOEL at a CD of 28.2 mg/kg and was supralinear at a high CD (282.2 mg/kg); (5) formation of preneoplastic hepatocellular altered foci (HAF) showed a NOEL at a CD of 28.2 mg/kg, and was supralinear at a high CD (282.2 mg/kg); (6) a NOEL (CD 28.2 mg/kg) was found for tumor development and the exposure—response was supralinear. We interpret these findings to reflect practical thresholds for hepatocellular initiating effects of AAF and exaggerated responses at high-exposures doses, as also found for DEN. Thus, mechanisms of carcinogenesis can differ between low and high doses.
The Toxicology of HMG—CoA Reductase Inhibitors: Prediction of Human Risk
Authors: MacDonald James S. , Halleck Margaretann M.
Published: July 2004

The discovery that 3-hydroxy-3-methyglutaryl coenzyme A reductase was a rate-determining step in the biosynthesis of cholesterol led to the discovery of inhibitors of this enzyme. To support the development of these agents (statins) as potential hypocholesterolemic drugs, a variety of preclinical studies were conducted in several animal species. Not unexpectedly due to the central role played by mevalonic acid and its products including cholesterol in development and maintenance of cellular homeostasis, administration of high dosage levels of these agents led to the expression of a broad variety of adverse effects in many different tissues. Using the tools of toxicologic pathology and classical risk assessment, these varied toxicities were evaluated by many groups relative to the conditions of use in human therapy and a perspective was developed on potential human risk. These approaches of mechanism-based risk assessment predicted that most of the adverse effects observed in animals would not be seen under conditions of human use and supported the successful introduction of one of the most important classes of human medicines.
An Econometric Contribution to the U.S. Defense—Growth Nexus: Evidence from Error Correction Model
Authors: Mehanna Rock-Antoine
Published: July 2004

Past and contemporary research has examined the relationship between military spending and economic growth and has reported mixed results. These conflicting findings are perhaps due to the methodologies employed. Consequently, this study employs a simple, parsimonious New Growth model to investigate the link between military spending and economic growth in the United States over the period 1/1959—1/2001 by adopting a more robust estimation technique. It follows the Johansen co-integration and error correction methodology coupled with vector autoregression (VAR) and innovation accounting techniques. Findings are robustly substantiated and reveal that military spending and growth have neither a statistical nor an economic impact on each other. This suggests that current U.S. political debates opposing or favoring military spending on the grounds of its economic merit are irrelevant.
The Correlates of War 2 International Governmental Organizations Data Version 2.0
Authors: Pevehouse Jon , Nordstrom Timothy , Warnke Kevin
Published: July 2004

This article summarizes the new Correlates of War 2 International Governmental Organizations (IGOs) data. The data in the Correlates of War IGO data sets capture state memberships in the network of international governmental organizations. The expanded version 2.0 updates the original Wallace and Singer (1970) data set to provide membership information from1964 to 2001. Following a brief review of the literature pertaining to IGOs and world politics, we provide descriptions of all three versions of the data (country-year, IGO-year, and joint dyadic membership), discuss coding rules and subsequent changes to the data, and present graphical representations of changes in the network of IGOs over time using all three versions of the data.
A Suggestion for Clarifying the Study of Dissent in Economics
Authors: Backhouse Roger E.
Published: July 2004

The answer to this question might seem obvious: like Everest, dissent and controversy are there. However, for most academic economists, dissent is negligible and controversy is far less important than it is commonly made out to be. To draw attention to disagreements between economists is to offer a distorted picture of what economics is about. Instead, they argue, the focus of attention should be on the enormous extent to which economists agree. From this perspective, dissent and controversy are not worth much attention. Another justification for studying controversy is that it is exciting. James Tobin once argued (explaining the appeal of Keynesian economics) that when you are young you like theoretical controversy: you like hearing about the good guys and the bad guys, and the idea of being on the side of progressive thought and against an encrusted orthodoxy. Similarly, historians are interested in dissent and controversy in much the same way that writers of thrillers are more interested in neighborhoods where murders happen than in ones where everyone just watches TV all day! What these answers have in common is that they associate controversy and dissent with the pathology of the subject. Disagreement is something to be avoided and which reflects badly on the profession. The most famous representative of this view was probably Alfred Marshall. In his attempt to establish economics as a science that carried authority with the public, he studiously refrained (most of the time) from entering into controversy, and he sought to reconcile within his own work divergent trends that were tearing apart the subject in other countries.
Mx1 GTPase accumulates in distinct nuclear domains and inhibits influenza A virus in cells that lack promyelocytic leukaemia protein nuclear bodies
Authors: Engelhardt Othmar G. , Sirma Hüseyin , Pandolfi Pier-Paolo , Haller Otto
Published: July 2004

The interferon-induced murine Mx1 GTPase is a nuclear protein. It specifically inhibits influenza A viruses at the step of primary transcription, a process known to occur in the nucleus of infected cells. However, the exact mechanism of inhibition is still poorly understood. The Mx1 GTPase has previously been shown to accumulate in distinct nuclear dots that are spatially associated with promyelocytic leukaemia protein (PML) nuclear bodies (NBs), but the significance of this association is not known. Here it is reported that, in cells lacking PML and, as a consequence, PML NBs, Mx1 still formed nuclear dots. These dots were indistinguishable from the dots observed in wild-type cells, indicating that intact PML NBs are not required for Mx1 dot formation. Furthermore, Mx1 retained its antiviral activity against influenza A virus in these PML-deficient cells, which were fully permissive for influenza A virus. Nuclear Mx proteins from other species showed a similar subnuclear distribution. This was also the case for the human MxA GTPase when this otherwise cytoplasmic protein was translocated into the nucleus by virtue of a foreign nuclear localization signal. Human MxA and mouse Mx1 do not interact or form heterooligomers. Yet, they co-localized to a large degree when co-expressed in the nucleus. Taken together, these findings suggest that Mx1 dots represent distinct nuclear domains (‘Mx nuclear domains’) that are frequently associated with, but functionally independent of, PML NBs.
Sequence analysis of human rhinoviruses in the RNA-dependent RNA polymerase coding region reveals large within-species variation
Authors: Savolainen Carita , Laine Pia , Mulders Mick N. , Hovi Tapani
Published: July 2004

Human rhinoviruses (HRVs; family Picornaviridae), the most frequent causative agents of respiratory infections, comprise more than 100 distinct serotypes. According to previous phylogenetic analysis of the VP4/VP2-coding sequences, all but one of the HRV prototype strains distribute between the two established species, Human rhinovirus A (HRV-A) and Human rhinovirus B (HRV-B). Here, partial sequences of the RNA-dependent RNA polymerase (3D polymerase)-coding gene of 48 HRV prototype strains and 12 field isolates were analysed. The designated division of the HRV strains into the species HRV-A and HRV-B was also seen in the 3D-coding region. Phylogenetically, HRV-B clustered closer to human enterovirus (HEV) species HEV-B, HEV-C and poliovirus than to HRV-A. Intraspecies variation within both HRV-A and HRV-B was greater in the 3D-coding region than in the VP4/VP2-coding region, with the difference maxima reaching 48 % at the nucleotide level and 36 % at the amino acid level in HRV-A and 53 and 35 %, respectively, in HRV-B. Within both species, a few strains formed a separate cluster differing from the majority of strains as much as HEV-B from HEV-C. Furthermore, the tree topology within HRV-A differed from that for VP4/VP2, suggesting possible recombination events in the evolutionary history of the strains. However, all 12 field isolates clustered similarly, as in the capsid region. These results showed that the within-species variation in the 3D region is greater in HRV than in HEV. Furthermore, HRV variation in the 3D region exceeds that in the capsid-coding region.
Potent virucidal activity in larval Heliothis virescens plasma against Helicoverpa zea single capsid nucleopolyhedrovirus
Authors: Popham Holly J. R. , Shelby Kent S. , Brandt Sandra L. , Coudron Thomas A.
Published: July 2004

Lepidopteran larvae resist baculovirus infection by selective apoptosis of infected midgut epithelial cells and by sloughing off infected cells from the midgut. Once the infection breaches the midgut epithelial barrier and propagates from infective foci to the haemocoel, however, there are few mechanisms known to account for the resistance and clearance of infection observed in some virus–host combinations. The hypothesis that factors present in the plasma of infected pest larvae act to limit the spread of virus from initial infective foci within the haemocoel was tested. An in vitro bioassay was developed in which Helicoverpa zea single capsid nucleopolyhedrovirus (HzSNPV) was incubated with plasma collected from uninfected Heliothis virescens larvae. Infectious HzSNPV particles were then titrated on HzAM1 cells. Diluted plasma from larval Heliothis virescens exhibited a virucidal effect against HzSNPV in vitro, reducing the TCID50 ml−1 by more than 64-fold (from 4·3±3·6×105 to 6·7±0·6×103). The antiviral activity was heat-labile but was unaffected by freezing. In addition, protease inhibitors and specific chemical inhibitors of phenol oxidase or prophenol oxidase activation added to diluted plasma eliminated the virucidal activity. Thus, in the plasma of larval lepidopterans, the enzyme phenol oxidase may act as a constitutive, humoral innate antiviral immune response.
Modified vaccinia virus Ankara induces moderate activation of human dendritic cells
Authors: Drillien Robert , Spehner Danièle , Hanau Daniel
Published: July 2004

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain known to be an effective vaccine vector. Here it is demonstrated that MVA, unlike standard vaccinia virus (VACV) strains, activates monocyte-derived human dendritic cells (DCs) as testified by an increase in surface co-stimulatory molecules and the secretion of pro-inflammatory cytokines. Inhibition of virus gene expression by subjecting MVA to UV light or heat treatment did not alter its ability to activate DCs. On the other hand, standard VACV strains activated DCs if virus gene expression was prevented by prior UV light or heat treatment. These results suggest that MVA or standard VACV particles are responsible for DC activation but, in the case of standard VACV strains, virus gene expression prevents activation. Additional experiments showed that DCs were activated by MVA-infected HeLa cells and, under these conditions, could induce secretion of gamma interferon from T lymphocytes more efficiently than if a replication-competent VACV strain was employed. These data provide one explanation for the remarkable immune-stimulating capacity of MVA in the absence of virus multiplication.
Functional properties of a 16 kDa protein translated from an alternative open reading frame of the core-encoding genomic region of hepatitis C virus
Authors: Basu Arnab , Steele Robert , Ray Ranjit , Ray Ratna B.
Published: July 2004

Hepatitis C virus (HCV) often causes persistent infection in humans. This could be due in part to the effect of viral proteins on cellular gene expression. Earlier observations suggest that the HCV core protein expressed from genotype 1a modulates important cellular genes at the transcriptional level, affects programmed cell death (apoptosis) and promotes cell growth. Recently, different groups of investigators have reported the translation of an ∼16 kDa protein (named F/ARFP/core+1 ORF) from an alternate open reading frame of the HCV core-encoding genomic region. The functional significance of this F protein is presently unknown. Thus, whether the F and core proteins have both shared and distinct functions was investigated here. The experimental observations suggested that the F protein does not significantly modulate c-myc, hTERT and p53 promoter activities, unlike the HCV core protein. Interestingly, the F protein repressed p21 expression. Further studies indicated that the F protein does not inhibit tumour necrosis factor alpha-mediated apoptosis of HepG2 cells or promote rat embryo fibroblast growth. Taken together, these results suggest that the F protein does not share major properties identified previously for the HCV core protein, other than regulating p21 expression.
Broad-spectrum detection of papillomaviruses in bovine teat papillomas and healthy teat skin
Authors: Ogawa Tomoko , Tomita Yoshimi , Okada Mineyuki , Shinozaki Kuniko , Kubonoya Hiroko , Kaiho Ikuo , Shirasawa Hiroshi
Published: July 2004

To investigate the prevalence of bovine papillomavirus (BPV) in bovine papilloma and healthy skin, DNA extracted from teat papillomas and healthy teat skin swabs was analysed by PCR using the primer pairs FAP59/FAP64 and MY09/MY11. Papillomavirus (PV) DNA was detected in all 15 papilloma specimens using FAP59/FAP64 and in 8 of the 15 papilloma specimens using MY09/MY11. In swab samples, 21 and 8 of the 122 samples were PV DNA positive using FAP59/FAP64 and MY09/MY11, respectively. Four BPV types (BPV-1, -3, -5 and -6), two previously identified putative BPV types (BAA1 and -5) and 11 putative new PV types (designated BAPV1 to -10 and BAPV11MY) were found in the 39 PV DNA-positive samples. Amino acid sequence alignments of the putative new PV types with reported BPVs and phylogenetic analyses of the putative new PV types with human and animal PV types showed that BAPV1 to -10 and BAPV11MY are putative new BPV types. These results also showed the genomic diversity and extent of subclinical infection of BPV.
Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages
Authors: Sirén Jukka , Sareneva Timo , Pirhonen Jaana , Strengell Mari , Veckman Ville , Julkunen Ilkka , Matikainen Sampsa
Published: July 2004

NK cells participate in innate immune responses by secreting gamma interferon (IFN-γ) and by destroying virus-infected cells. Here the interaction between influenza A or Sendai virus-infected macrophages and NK cells has been studied. A rapid, cell–cell contact-dependent production of IFN-γfrom NK cells cultured with virus-infected macrophages was observed. Expression of the MHC class I-related chain B (MICB) gene, a ligand for NK cell-activating receptor NKG2D, was upregulated in virus-infected macrophages suggesting a role for MICB in the activation of the IFN-γgene in NK cells. IL12Rβ2, IL18R and T-bet mRNA synthesis was enhanced in NK cells cultured with virus-infected macrophages. Upregulation of these genes was dependent on macrophage-derived IFN-α. In contrast to IL12Rβ2, expression of WSX-1/TCCR, a receptor for IL27, was reduced in NK cells in response to virus-induced IFN-α. In conclusion, these results show that virus-infected macrophages activate NK cells via cytokines and direct cellular interactions and further emphasize the role of IFN-αin the activation of innate immunity.
Immunization with dendritic cells can break immunological ignorance toward a persisting virus in the central nervous system and induce partial protection against intracerebral viral challenge
Authors: Fassnacht Ulrike , Ackermann Andreas , Staeheli Peter , Hausmann Jürgen
Published: July 2004

Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropicBorna disease virus(BDV) in mice was evaluated. Certain strains of mice only rarely develop spontaneous neurological disease, despite massive BDV replication in the brain. Resistance to disease is due to immunological ignorance toward BDV antigen in the central nervous system. Ignorance in mice can be broken by immunization with DCs coated with TELEISSI, a peptide derived from the N protein of BDV, which represents the immunodominant cytotoxic T lymphocyte epitope in H-2kmice. Immunization with TELEISSI-coated DCs further induced solid protective immunity against intravenous challenge with a recombinant vaccinia virus expressing BDV-N. Interestingly, however, this immunization scheme induced only moderate protection against intracerebral challenge with BDV, suggesting that immune memory raised against a shared antigen may be sufficient to control a peripherally replicating virus, but not a highly neurotropic virus that is able to avoid activation of T cells. This difference might be due to the lack of BDV-specific CD4 T cells and/or inefficient reactivation of DC-primed, BDV-specific CD8 T cells by the locally restricted BDV infection. Thus, a successful vaccine against persistent viruses with strong neurotropism should probably induce antiviral CD8 (as well as CD4) T-cell responses and should favour the accumulation of virus-specific memory T cells in cervical lymph nodes.
The Paradoxical Nature of The Relationship Between Training and Learning
Authors: Antonacopoulou Elena P.
Published: July 2004

The difficulty of explaining the paradoxical nature of organizational life has resulted in reductionist approaches, which present the relationships between processes as causal and linear. The relationship between training and economic performance, the contribution of training to individuals’ adaptability to change and the significance of knowledge and learning to organizational competitiveness are just some examples of the perceived linearity of the relationships between processes. The relationship between training and learning falls in the same category in that it is assumed to be very strong. This article makes a contribution to this debate by providing new insights about the relationship between training and learning. Using recent empirical findings from a longitudinal study in the Financial Services Sector, this article examines some of the basic differences between training and learning using the individual manager as the unit of analysis. These differences reveal some of the conditions that shape the relationship between training and learning. The findings from the study suggest that the relationship between training and learning may appear strong on the surface; however in essence it may be superficial and mechanistic.
The Negotiation of Purpose in Multi‐Organizational Collaborative Groups
Authors: Eden Colin , Huxham Chris
Published: July 2004

The negotiation and agreement of goals for collaborations between public and non‐profit organizations is argued to be a complex and painful process. Thus, the research described in this paper used action research to explore some of the critical behaviours in such groups. Based on the two units of analysis of ‘goal ownership’ and ‘episodes in negotiation’, a categorization of types of multi‐organizational group negotiation behaviour is developed. The categories are intended to be of practical use to those seeking to ensure the success of a collaboration.
Stakeholding: Confusion or Utopia? Mapping the Conceptual Terrain
Authors: Stoney Christopher , Winstanley Diana
Published: July 2004

The paper has three main objectives. The first aim is to examine and clarify the burgeoning stakeholder literature that currently seeks to inform management practice, corporate governance and public policy with particular emphasis on the UK. We do this by continuing the process of clarification started by Donaldson and Preston (1995), focusing mainly on the political and practitioner literature generated within the UK. We begin this task by setting out a critique of stakeholding and develop this by using four key themes of enquiry. First, we examine stakeholding’s conceptual confusion; second, we outline and develop criticism of its underlying pluralist assumptions; third, we consider the problems of implementation; and finally, we assess some of the key arguments concerning its potential impact on business performance and competitiveness.

The second aim is to develop and examine the central criticisms of stakeholding from both the neo‐liberal and Marxist/radical perspectives. By so doing we identify the key theoretical and practical issues which stakeholder proponents must address if they are to convince sceptics of the model’s validity.

The third aim is to develop a conceptual framework capable of illustrating the different stakeholder perspectives and assumptions on which they are based. This consists of five continuums: the first locates authors on a left–right political continuum; the second distinguishes between those authors who use stakeholding primarily for analysis and those who use it to formulate and prescribe specific courses of action; the third differentiates between intrinsic (good in itself) and instrumental (means to an end) motives; the fourth identifies the various levels of proposed intervention; and the fifth illustrates the different degrees of enforcement advocated.

We believe that this framework provides a clear illustration of our arguments and serves as a useful instrument for clarifying the stakeholder concept. In addition, it is used to position or map the work of key authors within the stakeholder debate and we believe it may provide a more coherent basis for future research and debate.
Hoshin Kanri: Policy Management In Japanese‐Owned UK Subsidiaries
Authors: Witcher Barry J. , Butterworth Rosemary
Published: July 2004

This paper presents the findings from an ESRC two‐year research project about Hoshin Kanri (policy management). Hoshin Kanri is a form of corporate‐wide management that combines strategic management and operational management by linking the achievement of top management goals with daily management at an operation level. The research explored practice in real time in three Japanese manufacturing UK‐based subsidiaries. This paper consists of: an introductory review of the Hoshin Kanri and Japanization literature; a description of the research and a presentation of the three case studies and the main specific issues; and a discussion of the model and the parts played by lean working and TQM, catchball and nemawashi, strategic management, and the uniqueness of Hoshin Kanri, especially in relation to conventional planning, MBO (management by objectives), and the balanced scorecard. Hoshin Kanri is found to be an organizing framework for policy‐based objectives. These are translated into QCDE (quality, cost, delivery, education) targets which are used in daily management to drive progress. Hoshin Kanri employs a participative approach to developing and deploying objectives, and is driven by a process of review. Hoshin Kanri must be managed as a process. Some of the main issues include changes in organization and personnel, problems with administering periodic review, and cross‐functional working in departmental forms of organization.
The New International Division of Labour in Asian Electronics: Work Organization and Human Resources in Japan and Malaysia
Authors: Wilkinson Barry , Gamble Jos , Humphrey John , Morris Jonathan , Anthony Doug
Published: July 2004

This article documents and analyses the organization of work and human resources management in ten manufacturing plants in Malaysia and three plants in Japan. Each of the plants carries out specific tasks within an emergent international division of labour surrounding two Japanese multinational producers of consumer electronics goods. Plant roles reflect their positions in commodity chains driven by the multinationals, varying in relation to product‐to‐product and component‐to‐component divisions of labour, and in relation to the location of product and process innovations. How work is organized and how workers are managed are explained by the location of each plant within this division of labour, and by the characteristics and situation of labour, the one commodity which talks back, within the local environment.
Markets, Culture and Institutions: The Emergence of Large Business Groups in Taiwan, 1950s–1970s
Authors: Chung Chi‐nien
Published: July 2004

Business groups are a special type of enterprise system existing in almost every market economy. Member firms do not operate as isolated units in the markets but have institutionalized relationships with each other and work coherently as an entity. Groups play a central role in economies in which they operate. For Taiwan, the largest 100 groups produced one third of the GNP in the past 20 years. Why does this organizational form exist in the first place? This paper reviews three relevant theories, market‐centred theories, culturalist perspective, and the institutional approach, and employs the data of 150 Taiwanese groups for the answer. The market‐centred theories and the institutional arguments are examined statistically and the latter is supported by the data. Following this evidence, the Boolean comparison of group firms with non‐group firms confirms that lacking a coherent core in ownership and management makes firms unable to respond to institutional incentives promptly. Finally, the structure of family ownership network in business groups refutes the cultural perspective which argues that the equal inheritance pattern of family property drives entrepreneurs to establish separate firms rather than single hierarchies. While both markets and culture play a distinct part in the story, it is regulatory institutions that lead to group formation.
Genetic counseling for familial conditions during pregnancy: an analysis of patient characteristics
Authors: Aalfs CM , Mollema ED , Oort FJ , De Haes JCJM , Leschot NJ , Smets EMA
Published: July 2004

Reproductive genetic counseling for a familial genetic risk factor preferably takes place before conception. However, of the women with a family history of genetic conditions who attend our department of clinical genetics, about 10–20% attend for the first time during a pregnancy. The current study aims to explore patient‐related factors that may affect this late timing of reproductive genetic counseling. Consecutive pregnant (n = 100) and non‐pregnant (n = 84) women visiting the department of clinical genetics for a genetic risk factor which was not age related completed a questionnaire immediately prior to the consultation. The questionnaire asked for (a) background characteristics, i.e. socio‐demographic, obstetric, and disease characteristics (b) cognitive factors, i.e. initiative of referral, knowledge of the risk factor involved, risk perception, worry, child wish, attitudes toward abortion, and preferred participation in decision making, and (c) reasons for the timing of the consultation and for seeking genetic counseling. Pregnant women appeared to be higher educated, considered their children more often as healthy and were less often affected themselves, as compared to non‐pregnant women. They also estimated their chance of having an affected child as lower, and they worried less. Furthermore, the initiative for referral was taken less often by the pregnant woman herself and more often by a medical worker. There were no major differences between the two study groups in knowledge, perceived severity of the risk factor, child wish, attitudes toward abortion, desired participation in decision making, and reasons to seek genetic counseling. Women indicated no specific reasons for their timing of referral for reproductive genetic counseling, e.g. during vs before pregnancy. Our data suggest that this timing of referral is not influenced predominantly by the women's level of knowledge. Rather, women's estimation of genetic risks and their degree of worry, which may be in accordance with the actual risk figures, seem to play a role in seeking genetic counseling. Although further studies are required, a more active role of health care providers seems warranted if we want to prevent genetic counseling for familial genetic conditions during pregnancy as much as possible.
Fishing for new genes in skin biology: impact of cytogenetics on gene discovery
Authors: Tadin‐Strapps M , Warburton D , Salas‐Alanis JC , Lopez‐Cepeda LD , Christiano AM
Published: July 2004

Research into the field of skin biology has grown exponentially over the past two decades. Even though the fundamental molecular pathways are still not fully understood, there have been significant advances in our understanding of the underlying mechanisms involved in the pathogenesis of genodermatosis. The cloning of many candidate genes involved in the etiology of skin diseases has been facilitated by initial cytogenetic evidence. This review will synthesize recent findings that led to the discovery of candidate genes for anhidrotic ectodermal dysplasia, Williams‐Beuren syndrome, neurofibromatosis‐I and tricho‐rhino‐phalangeal syndrome.
Malignant Refractory Epilepsy in Identical Twins Mosaic for a Supernumerary Ring Chromosome 19
Authors: Shahwan Amre , Green Andrew J. , Carey Aiveen , Stallings Raymond L. , O'Flaherty Odette C. , King Mary D.
Published: July 2004

Summary:  We report identical twins with supernumerary ring chromosome 19 mosaicism, who had severe refractory epilepsy at an early age. The epilepsy was dominated largely by severe life‐threatening tonic seizures. Both twins died, likely as a consequence of their severe epilepsy. They displayed no dysmorphic features. Eight cases of ring chromosome 19 have been reported in the literature, all to our knowledge without epilepsy. The clinical picture of these twins emphasizes the importance of carrying out a karyotype study on patients with early‐onset epilepsy even in the absence of dysmorphic features.
Todd, Faraday, and the Electrical Basis of Epilepsy
Authors: Reynolds Edward H.
Published: July 2004

Summary:  Purpose: To consider the origins of our understanding of the electrical basis of epilepsy in the light of the Lumleian lectures to the Royal College of Physicians in London for 1849, “On the pathology and treatment of convulsive diseases,” by Robert Bentley Todd (1809–1860).

Methods: I have reviewed Todd's neglected Lumleian lectures and his observations and concepts of the electrical basis of epilepsy in relation to the influence of Michael Faraday (1791–1867), his contemporary in London, and in relation to later nineteenth century writings on the subject by Jackson, Ferrier, and Hitzig, all of whom overlooked Todd's lectures.

Results: Todd was a clinical scientist as well as Professor of Physiology and Morbid Anatomy, with a special interest in the nervous system, at King's College, where he came into contact with Michael Faraday, the greatest electrical scientist of all time, at the nearby Royal Institution. On the basis of his own clinical and experimental studies and his cutting‐edge knowledge of neuroanatomy, neurophysiology, neuropathology, and electrical science, Todd brilliantly developed his concepts of the electrical basis of brain activity and of epilepsy in particular. With his microscope, he perceived each nerve vesicle and its related fibres (neurone in later terminology) as distinct entities for the generation of nervous polarity (force) and its transmission in the white nerve fibres throughout the nervous system by unknown molecular mechanisms. In epilepsy, an increase in electrical tension, especially in the grey matter of the hemispheres, led to periodic, sudden explosive discharges, based on Faraday's concept of disruptive discharges.

Conclusions: Todd was the United Kingdom's first outstanding neurologist and neuroscientist before these disciplines existed. Influenced by Faraday, he proposed and confirmed the electrical basis of nervous discharges in epilepsy more than 20 years ahead of Jackson, Ferrier, and Hitzig, who did not refer to his priority, although Ferrier also worked at King's College, and Jackson also gave his own famous Lumleian lectures on the same subject in 1890. Todd deserves the credit for laying the foundations of our modern understanding of epilepsy.
Dialyzability of the Antiepileptic Drug Zonisamide in Patients Undergoing Hemodialysis
Authors: Ijiri Yoshio , Inoue Toru , Fukuda Fumio , Suzuki Kaoru , Kobayashi Toyohide , Shibahara Nobuhisa , Takenaka Hiroshi , Tanaka Kazuhiko
Published: July 2004

Summary:  Purpose: The influence of hemodialysis on plasma zonisamide (ZNS) concentration has not been clarified. In this study, the dialyzability of ZNS during hemodialysis was investigated in four ZNS‐treated women with systemic lupus erythematosus complicated by seizures.

Methods: The total and unbound plasma concentrations of ZNS were measured before and after hemodialysis. The concentration of ZNS in the spent dialysate also was determined.

Results: The reduction in plasma ZNS concentration after a 4.5‐h hemodialysis was 52.0 ± 7.6%, and the dialyzer (BLF‐16GW) clearance of ZNS was 55.1 ± 7.0 ml/min. Dosage was gradually increased up to 200 to 500 mg/day, and the seizures were controlled satisfactorily.

Conclusions: The plasma concentration of ZNS was reduced by approximately 50% during one session of dialysis. For patients undergoing daytime hemodialysis sessions every 2 or 3 days, the usual dosage of ZNS (4–8 mg/kg/day) may be prescribed once a day in the evening. If seizures occur after hemodialysis, a supplemental daily dose may be prescribed in the morning.