bluuebunny/crossref_metadata_2025 huggingface dataset:
e‐Integration in the Supply Chain: Barriers and Performance*
Authors: Frohlich Markham T.
Published: June 2007

Current opinion holds that Internet‐based supply chain integration with upstream suppliers and downstream customers (called “e‐integration” in this paper) is superior to traditional ways of doing business. This proposition remains untested, however, and similarly we know little about what are the upstream, internal, and downstream barriers to implementing e‐integration. This paper empirically addressed these questions using data from a large single nation study, and found (1) a positive link between e‐integration and performance, and (2) that internal barriers impeded e‐integration more than either upstream supplier barriers or downstream customer barriers. Findings from this study contribute to our theoretical understanding of implementing change in contemporary supply chains, and have important implications for manufacturers interested in improving their supply chain's performance using the Internet.
Population structure and partial anadromy in Oncorhynchus mykiss from Kamchatka: relevance for conservation strategies around the Pacific Rim
Authors: McPhee M. V. , Utter F. , Stanford J. A. , Kuzishchin K. V. , Savvaitova K. A. , Pavlov D. S. , Allendorf F. W.
Published: June 2007

Abstract –  Conservation of life‐history diversity found in Oncorhynchus mykiss requires knowledge of the underlying population structure and genetic basis of this variability. We analysed variation at 10 microsatellite loci from seven rivers across Kamchatka to identify population structure and to test for divergence between life‐history forms. We found lower heterozygosity in Kamchatkan populations compared with North American populations, but population structure was substantial (region‐wide FST = 0.11) and followed an isolation‐by‐distance pattern similar to that reported for older North American populations. We found no evidence for genetic divergence between resident and anadromous individuals in the Sopochnaya River or between typically anadromous individuals and ‘half‐pounders’ in the Utkholok River. A review of other studies of reproductive isolation, in combination with our results, suggests: (1) that pristine populations of steelhead should be expected to exhibit partial anadromy; and (2) that managing anadromous and resident individuals separately without demonstrating reproductive isolation is biologically unsound.
Effects of bisphosphonate on the mandible of rats in the growing phase with steroid‐induced osteoporosis
Authors: Kimura E , Nishioka T , Hasegawa K , Maki K
Published: June 2007

Aim:  The objective of this study was to investigate the effects of bisphosphonate on the mandible of rats in the growing phase with steroid‐induced osteoporosis, and to estimate the biomechanical response in the mandibular bone.

Materials and methods:  Eight‐week‐old male Wistar rats (n = 50) were assigned to a 6‐week control (Co‐6) group, 6‐week steroid (St) group, 9‐week control (Co‐9) group, 9‐week steroid + standard diet (StSD) group, or 9‐week steroid + standard diet + bisphosphonate (StSDBp) group. The mandibular bone was evaluated by two‐dimensional bone density measurement (PDS‐15), three‐dimensional pQCT, and quantitative analysis of Ca, P, Mg, and Zn using a sequential high frequency plasma spectrometer (ICPS‐8000).

Results:  In PDS‐15 analysis, the bone density converted to aluminum equivalent was higher in StSDBp group when compared with the StSD group, and no significant difference was observed in bone density between St group and Co‐6 group. In pQCT analysis, trabecular bone density and mineral content were significantly higher, while all other bone parameters were significantly lower in St group when compared with the Co‐6 group. The densities of trabecular and cortical bones, mineral content and cross‐sectional area of cortical bone, and non‐invasive stress strain index with reference to x and yaxes were higher in StSDBp group than in StSD group. In quantitative analyses, Ca and P were markedly higher in StSDBp group than in StSD group, while there were no differences in Mg and Zn.

Conclusion:  Bisphosphonate treatment increases trabecular and cortical bone parameters in the mandible of growing rats with steroid‐induced osteoporosis.
A polygenic heterogeneity model for common epilepsies with complex genetics
Authors: Dibbens L. M. , Heron S. E. , Mulley J. C.
Published: June 2007

Approximately 40% of epilepsy has a complex genetic basis with an unknown number of susceptibility genes. The effect of each susceptibility gene acting alone is insufficient to account for seizure phenotypes, but certain numbers or combinations of variations in susceptibility genes are predicted to raise the level of neuronal hyperexcitability above a seizure threshold for a given individual in a given environment. Identities of susceptibility genes are beginning to be determined, initially by translation of knowledge gained from gene discovery in the monogenic epilepsies. This entrée into idiopathic epilepsies with complex genetics has led to the experimental validation of susceptibility variants in the first few susceptibility genes. The genetic architecture so far emerging from these results is consistent with what we have designated as a polygenic heterogeneity model for the epilepsies with complex genetics.
Elevated levels of human endogenous retrovirus‐W transcripts in blood cells from patients with first episode schizophrenia
Authors: Yao Y. , Schröder J. , Nellåker C. , Bottmer C. , Bachmann S. , Yolken R. H. , Karlsson H.
Published: June 2007

We previously reported on the differential presence of transcripts related to the human endogenous retrovirus (HERV)‐W family in cerebrospinal fluid and plasma from patients with first‐episode schizophrenia compared with control individuals. Whether this is a consequence of qualitative or quantitative differences in transcription of genomic regions harboring HERV‐W elements is not known. The purpose of the present study was therefore to characterize the transcribed HERV‐W elements in mononuclear cells obtained from 30 patients first hospitalized for schizophrenia‐related psychosis and from 26 healthy control individuals. We observed elevated total levels of HERV‐Wgag(2.1‐fold,P< 0.01) but notenvtranscripts in the cells of patients compared with controls. By using the melting temperatures of the amplicons as a proxy marker for sequence identity, no absolute qualitative differences was detected between the two groups. Mapping of the detected transcripts identified several intronic and intergenic HERV‐W elements transcribed in the cells, including elements previously considered transcriptionally silent. Element‐specific assays revealed elevated levels of intronic transcripts containing HERV‐Wgagsequence from the putative gene PTD015 on chromosome 11q13.5 (1.6‐fold,P< 0.05) in the patients compared with the controls. Thus, studies aiming to further understanding of complex human disease such as schizophrenia may need to be extended beyond the strictly protein‐coding fraction of the transcriptome.
The Timing of Entry into a New Market: An Empirical Study of Taiwanese Firms in China
Authors: Tan Danchi , Hung Shih-Chang , Liu Nienchi
Published: June 2007

This study examines the determinants of the timing of Taiwanese firms' entry into China. Our empirical findings suggest that this strategic decision is influenced by both economic and institutional concerns. In particular, we found that Taiwanese firms that expected greater benefits from early entry tended to be early entrants in China, while those that were more sensitive to uncertainty chose to defer their entry. We also found a curvilinear relationship between firm size and timing of entry into China. Our findings further indicate that the negative relationship between investment irreversibility and early entry is weaker in the presence of substantial perceived first mover advantages.
Tim Holt
Authors: Holt Tim , Champkin Julian
Published: June 2007

Tim Holt Outgoing President of the Royal Statistical Society. Julian Champkin spoke to him about life and statistical independence.
Career Story: Opinion Poll Statistician
Authors: Kemp Bess
Published: June 2007

Bess Kemp works as a statistician for National Opinion Polls, the people who survey us to find out what we buy, what we watch, what we think. She tells all.
FISHING IN DIFFERENT PONDS: UNION ORGANIZING ACROSS INDUSTRIES
Authors: Chandler Timothy D. , Gely Rafael
Published: June 2007

A major complaint of the Change to Win Coalition (“Coalition”) is the American Federation of Labor‐Congress of Industrial Organizations’ failure to “follow the work” and allocate sufficient resources to organizing, particularly in industries experiencing job growth. Our article uses industry‐level data from National Labor Relations Board‐supervised elections from 1970 to 2000 to evaluate the validity of this criticism. We find support for the Coalition's claim. Most industrial groups faired better than manufacturing in election outcomes. Yet union organizing activity was lower in other industries. Moreover, declining organizing activity within manufacturing suggests that other industries, most notably services, account for an even greater share of new entrants into the labor movement.
SHOULD UNIONS PLAY GOLF WITH REPUBLICANS?: LABOR PAC SUPPORT ACROSS POLITICAL PARTIES
Authors: Zullo Roland
Published: June 2007

This essay examines the strategy of political voluntarism, defined as a neutral political affiliation, by testing whether or not union political action committee (PAC) donations to congresspersons in the 2000 election cycle affected their roll call votes in subsequent years. Results indicate that overall, the Republicans became more antilabor in their roll call patterns after the election of George W. Bush, and that labor PAC donations did not moderate this shift. Democrats, however, became more prolabor in their roll call voting, and this trend was likewise independent of labor support. Finally, there is no evidence that congresspersons retaliated against labor when an electoral rival was supported. These findings underscore the importance of political parties in shaping public policy and challenge the utility of a labor political strategy that is party neutral. A strategic alternative, political idealism, is discussed.
PICKING CHERRIES WITH BLINDERS ON: A COMMENT ON ERICKSON ET AL. (2007) REGARDING THE USE OF TESTS IN FAMILY COURT*
Authors: Erard Robert E.
Published: June 2007

Erickson, Lilienfeld, and Vitacco's (2007/this issue) review of the suitability and limitations of psychological tests invites legal and mental health professionals to rely on it as an objective guide for selecting, using, and admitting psychological tests in family court matters. Unfortunately, their discussion is marred by a pronounced bias in favor of multiscale, objective personality inventories and against performance‐based or projective instruments. This bias is evident not only in their unbalanced emphasis on the strengths of the former and weaknesses of the latter, but also in their use of selective citations and loaded language in launching what amounts to a polemical argument in support of tests that they favor. Their discussion of the Rorschach inkblot test is particularly misleading. This article refutes their unwarranted criticisms of the theoretical underpinnings of the Rorschach test, its research base, its norms, its interscorer reliability, the validity of its scores, and its admissibility in the courtroom. The value of multimethod assessments that include the use of direct clinical observation of performance under standardized conditions in custody evaluations is highlighted.
CHILD RELOCATION: AN INTRACTABLE INTERNATIONAL FAMILY LAW PROBLEM
Authors: Carmody Justice Tim
Published: June 2007

This article examines the current state of the law on child relocation across the major common law‐based jurisdictions, with particular emphasis on the contrasting approaches to the problem in Australia and the United Kingdom. It then goes on to suggest changes aimed at achieving more principled and predictable outcomes.
THIN‐LAYER DRYING KINETICS OF SESAME HULLS UNDER FORCED CONVECTION AND OPEN SUN DRYING
Authors: AL‐MAHASNEH MAJDI A. , RABABAH TAHA M. , AL‐SHBOOL MOHAMMAD A. , YANG W.
Published: June 2007

Sesame hulls are a useful by‐product of the sesame processing industry. The sesame hulls are produced at a high moisture content (68% wet basis) and need further drying to prevent deterioration. In this study, both open sun drying (OSD) and forced convection drying (FCD) at 42, 55, and 76C and 1.2 m/s air velocity were investigated. Six common thin‐layer drying models were fitted to the experimental data. Several statistical parameters were used to evaluate the performance of thin‐layer drying models, including r2, x2, root mean square error (RMSE) and residuals. Sesame hull drying was found to take place completely in the falling rate region. The modified Page model was found to describe OSD data well, while the Wang and Singh model was the best model for describing FCD. Effective diffusivity was found to be 1.89 × 10‐8 m2/s and 7.36 × 10‐10 to 1.20 × 10‐9 m2/s for OSD and FCD, respectively. Activation energy was also found to be 12.95 kJ/mol for FCD.
Whose autonomy matters? Reconciling the competing claims of privacy and freedom of expression
Authors: Gomery Geoffrey
Published: June 2007

English law has recently recognised a tort of misuse of private information through the development of the tort of breach of confidence. This paper considers the conceptual issues that arise in the particular context of cases contesting the privacy of information exchanged in an intimate relationship. The courts have said that the purpose of protecting privacy through the tort is the promotion of individual autonomy. Examining what is entailed in this approach, it is argued that cases involving shared privacies can only be understood as involving the indirect promotion of autonomy through the protection of certain socially sanctioned relationships. A framework of analysis is developed under which the underlying issues are laid bare and through which the reasoning of the courts may be understood and criticised.
Making amends or making things worse? Clinical negligence reform and patient redress in England
Authors: Farrell Anne-Maree , Devaney Sarah
Published: June 2007

This paper examines the government’s reform of the current system of clinical negligence litigation in England, focusing on an analysis of the redress scheme for low value claims to be established under the NHS Redress Act 2006. The Act establishes a scheme to provide a package of redress to patients in circumstances where they have suffered harm as a result of negligence during the course of medical treatment provided by the NHS. One of the British Government’s central aims in embarking upon reform in this area was to provide a low cost, quick and genuine alternative to the current clinical negligence litigation system. This paper critically analyses this reform of the current system by reference to an examination of what constitutes a just redress scheme in the circumstances. Such analysis shows that the government has missed a golden opportunity to establish a scheme which truly ‘makes amends’ to patients who have suffered harm through medical treatment in the NHS. Instead, the scheme is likely to operate in practice as an administrative scheme for low value claims that serves the institutional and financial interests of the NHS, and therefore fails to address longstanding patient concerns over the provision of redress arising out of harm suffered through medical treatment. As a result, patient confidence in the scheme is likely to be undermined in the long term.
A Multilevel Exploration
Authors: Jablonski David
Published: June 2007

Evolution and the Levels of Selection
.
By Samir Okasha
. Clarendon Press, Oxford, 2006. 275 pp. $55, £30. ISBN 9780199267972.

Considering conceptual and foundational aspects of the debates over levels of selection--natural selection acting on genes, individuals, groups, or species--Okasha pays particular attention to effects that filter from one level up or down to others.
Stepwise Quenching of Exciton Fluorescence in Carbon Nanotubes by Single-Molecule Reactions
Authors: Cognet Laurent , Tsyboulski Dmitri A. , Rocha John-David R. , Doyle Condell D. , Tour James M. , Weisman R. Bruce
Published: June 2007

Single-molecule chemical reactions with individual single-walled carbon nanotubes were observed through near-infrared photoluminescence microscopy. The emission intensity within distinct submicrometer segments of single nanotubes changed in discrete steps after exposure to acid, base, or diazonium reactants. The steps were uncorrelated in space and time and reflected the quenching of mobile excitons at localized sites of reversible or irreversible chemical attack. Analysis of step amplitudes revealed an exciton diffusional range of about 90 nanometers, independent of nanotube structure. Each exciton visited about 10,000 atomic sites during its lifetime, providing highly efficient sensing of local chemical and physical perturbations.
Evaluation of a New Chromogenic Medium, chromID VRE, for Detection of Vancomycin-Resistant Enterococci in Stool Samples and Rectal Swabs
Authors: Delmas Julien , Robin Frédéric , Schweitzer Cédric , Lesens Olivier , Bonnet Richard
Published: June 2007

We compared ChromID VRE medium with Enterococcosel containing vancomycin for the detection of vancomycin-resistant
Enterococcus
in 1,007 specimens. ChromID VRE in combination with Gram straining provided a higher specificity than Enterococcosel, irrespective of the incubation time and enrichment.
Shelf Life of Predosed Plates Containing Mefloquine, Artemisinin, Dihydroartemisinin, and Artesunate as Used for In Vitro
Plasmodium falciparum
Susceptibility Assessment
Authors: Houzé Sandrine , Munier Aline , Paoletti Xavier , Kaddouri Halima , Ringwald Pascal , Le Bras Jacques
Published: June 2007

The shelf lives of preserved antimalarial agent-predosed plates according to the type of wrapping and the temperature of storage were studied by measuring the 50% inhibitory concentrations of drug for
Plasmodium falciparum
3D7. The shelf life of mefloquine was 8 weeks at 25°C; and those of artesunate, artemisinin, and dihydroartemisinin were a minimum of 24, 12, and 8 weeks, respectively, at 4°C.
Vpr Cytopathicity Independent of G
2
/M Cell Cycle Arrest in Human Immunodeficiency Virus Type 1-Infected CD4
+
T Cells
Authors: Bolton Diane L. , Lenardo Michael J.
Published: June 2007

The mechanism of CD4
+
T-cell depletion in human immunodeficiency virus type 1 (HIV-1)-infected individuals remains unknown, although mounting evidence suggests that direct viral cytopathicity contributes to this loss. The HIV-1 Vpr accessory protein causes cell death and arrests cells in the G
2
/M phase; however, the molecular mechanism underlying these properties is not clear. Mutation of hydrophobic residues on the surface of its third alpha-helix disrupted Vpr toxicity, G
2
/M arrest induction, nuclear localization, and self-association, implicating this region in multiple Vpr functions. Cytopathicity by virion-delivered mutant Vpr protein correlated with G
2
/M arrest induction but not nuclear localization or self-association. However, infection with whole virus encoding these Vpr mutants did not abrogate HIV-1-induced cell killing. Rather, mutant Vpr proteins that are impaired for G
2
/M block still prevented infected cell proliferation, and this property correlated with the death of infected cells. Chemical agents that inhibit infected cells from entering G
2
/M also did not reduce HIV-1 cytopathicity. Combined, these data implicate Vpr in HIV-1 killing through a mechanism involving inhibiting cell division but not necessarily in G
2
/M. Thus, the hydrophobic region of the third alpha-helix of Vpr is crucial for mediating G
2
/M arrest, nuclear localization, and self-association but dispensable for HIV-1 cytopathicity due to residual cell proliferation blockade mediated by a separate region of the protein.
A Mutation in the Human Herpes Simplex Virus Type 1 UL52 Zinc Finger Motif Results in Defective Primase Activity but Can Recruit Viral Polymerase and Support Viral Replication Efficiently
Authors: Chen Yan , Livingston Christine M. , Carrington-Lawrence Stacy D. , Bai Ping , Weller Sandra K.
Published: June 2007

Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase/primase complex consisting of UL5, UL8, and UL52. UL5 contains conserved helicase motifs, while UL52 contains conserved primase motifs, including a zinc finger motif. Although HSV-1 and HSV-2 UL52s contain a leucine residue at position 986, most other herpesvirus primase homologues contain a phenylalanine at this position. We constructed an HSV-1 UL52 L986F mutation and found that it can complement a UL52 null virus more efficiently than the wild type (WT). We thus predicted that the UL5/8/52 complex containing the L986F mutation might posses increased primase activity; however, it exhibited only 25% of the WT level of primase activity. Interestingly, the mutant complex displayed elevated levels of DNA binding and single-stranded DNA-dependent ATPase and helicase activities. This result confirms a complex interdependence between the helicase and primase subunits. We previously showed that primase-defective mutants failed to recruit the polymerase catalytic subunit UL30 to prereplicative sites, suggesting that an active primase, or primer synthesis, is required for polymerase recruitment. Although L986F exhibits decreased primase activity, it can support efficient replication and recruit UL30 efficiently to replication compartments, indicating that a partially active primase is capable of recruiting polymerase. Extraction with detergents prior to fixation can extract nucleosolic proteins but not proteins bound to chromatin or the nuclear matrix. We showed that UL30 was extracted from replication compartments while UL42 remained bound, suggesting that UL30 may be tethered to the replication fork by protein-protein interactions.
Decreased CXCR3+CD8 T Cells in Advanced Human Immunodeficiency Virus Infection Suggest that a Homing Defect Contributes to Cytotoxic T-Lymphocyte Dysfunction
Authors: Brainard Diana M. , Tager Andrew M. , Misdraji Joseph , Frahm Nicole , Lichterfeld Mathias , Draenert Rika , Brander Christian , Walker Bruce D. , Luster Andrew D.
Published: June 2007

To exert their cytotoxic function, cytotoxic T-lymphocytes (CTL) must be recruited into infected lymphoid tissue where the majority of human immunodeficiency virus (HIV) replication occurs. Normally, effector T cells exit lymph nodes (LNs) and home to peripheral sites of infection. How HIV-specific CTL migrate into lymphoid tissue from which they are normally excluded is unknown. We investigated which chemokines and receptors mediate this reverse homing and whether impairment of this homing could contribute to CTL dysfunction as HIV infection progresses. Analysis of CTL chemokine receptor expression in the blood and LNs of untreated HIV-infected individuals with stable, chronic infection or advanced disease demonstrated that LNs were enriched for CXCR3+CD8 T cells in all subjects, suggesting a key role for this receptor in CTL homing to infected lymphoid tissue. Compared to subjects with chronic infection, however, subjects with advanced disease had fewer CXCR3+CD8 T cells in blood and LNs. CXCR3 expression on bulk and HIV-specific CD8 T cells correlated positively with CD4 count and negatively with viral load. In advanced infection, there was an accumulation of HIV-specific CD8 T cells at the effector memory stage; however, decreased numbers of CXCR3+CD8 T cells were seen across all maturation subsets. Plasma CXCL9 and CXCL10 were elevated in both infected groups in comparison to the levels in uninfected controls, whereas lower mRNA levels of CXCR3 ligands and CD8 in LNs were seen in advanced infection. These data suggest that both CXCR3+CD8 T cells and LN CXCR3 ligands decrease as HIV infection progresses, resulting in reduced homing of CTL into LNs and contributing to immune dysfunction.
Cyclosporine Inhibits Mouse Cytomegalovirus Infection via a Cyclophilin-Dependent Pathway Specifically in Neural Stem/Progenitor Cells
Authors: Kawasaki Hideya , Mocarski Edward S. , Kosugi Isao , Tsutsui Yoshihiro
Published: June 2007

The potential of neural stem and progenitor cell (NSPC) transplantation in neurodegenerative disease raises a concern about immunosuppressive agents and opportunistic neurotropic pathogens that may interfere with engraftment. Cytomegalovirus (CMV) is an important opportunistic pathogen infecting the central nervous system, where it may remain latent for life, following transplacental transmission. Cyclosporine (Cs), an immunosuppressive drug used in organ transplantation, where its use is associated with CMV reactivation, suppressed murine CMV (MCMV) infection in cultured NSPCs but not in fibroblasts. This activity of Cs appears to be mediated via cyclophilin (CyP) rather than via calcineurin. First, the calcineurin-specific inhibitor FK506 failed to suppress replication. Second, the CyP-specific inhibitor NIM811 strongly suppressed replication in NSPC. NSPCs maintained in the presence of NIM811 retained viral genomes for several weeks without detectable viral gene expression or obvious deleterious effects. The withdrawal of NIM811 reactivated viral replication, suggesting that the inhibitory mechanism was reversible. Finally, inhibition of endogenous CyP A (CyPA) by small interfering RNA also inhibited replication in NSPCs. These results show that MCMV replication depends upon cellular CyPA pathways in NSPCs (in a specific cell type-dependent fashion), that CyPA plays an important role in viral infection in this cell type, and that inhibition of viral replication via CyP leads to persistence of the viral genome without cell damage. Further, the calcineurin-signaling pathway conferring immunosuppression in T cells does not influence viral replication in a detectable fashion.
Environment Determines Fidelity for an RNA Virus Replicase
Authors: Pita Justin S. , de Miranda Joachim R. , Schneider William L. , Roossinck Marilyn J.
Published: June 2007

The rate of insertion and deletion mutations of the replicase of
Cucumber mosaic virus
(CMV) was determined in planta by using a parasitic satellite RNA (satRNA) as a reporter. We found that the CMV replicase had different fidelity in different environments, with important implications in viral disease evolution. Insertions were very rare events, irrespective of the region of the satRNA genome assayed and independent of the hosts tested. On the other hand, deletion events were more frequent but were restricted to a highly structured region of the reporter. Deletion mutation rates were different for the two hosts tested, although the mutation distribution was not influenced by the hosts. Moreover, hot spots with high mutation rates were identified on the satRNA genome.
Two Distinct Low-pH Steps Promote Entry of Vaccinia Virus
Authors: Townsley Alan C. , Moss Bernard
Published: June 2007

Entry of vaccinia virus into cells occurs by an endosomal route as well as through the plasma membrane. Evidence for an endosomal pathway was based on findings that treatment at a pH of <6 of mature virions attached to the plasma membrane enhances entry, whereas inhibitors of endosomal acidification reduce entry. Inactivation of infectivity by low-pH treatment of virions prior to membrane attachment is characteristic of many viruses that use the endosomal route. Nevertheless, we show here that the exposure of unattached vaccinia virus virions to low pH at 37°C did not alter their infectivity. Instead, such treatment stably activated virions as indicated by their accelerated entry upon subsequent addition to cells, as measured by reporter gene expression. Moreover, the rate of entry was not further enhanced by a second low-pH treatment following adsorption to the plasma membrane. However, the entry of virions activated prior to adsorption remained sensitive to inhibitors of endosomal acidification, whereas virions treated with low pH after adsorption were resistant. Activation of virions by low pH was closely mimicked by proteinase digestion, suggesting that the two treatments operate through a related mechanism. Although proteinase cleavage of the virion surface proteins D8 and A27 correlated with activation, mutant viruses constructed by individually deleting these genes did not exhibit an activated phenotype. We propose a two-step model of vaccinia virus entry through endosomes, in which activating or unmasking the fusion complex by low pH or by proteinase is rate limiting but does not eliminate a second low-pH step mediating membrane fusion.
Targeting of Adenovirus Serotype 5 (Ad5) and 5/47 Pseudotyped Vectors In Vivo: Fundamental Involvement of Coagulation Factors and Redundancy of CAR Binding by Ad5
Authors: Waddington Simon N. , Parker Alan L. , Havenga Menzo , Nicklin Stuart A. , Buckley Suzanne M. K. , McVey John H. , Baker Andrew H.
Published: June 2007

Vitamin K-dependent coagulation factors can promote adenoviral cell transduction in vitro. In vivo, warfarin pretreatment ablates liver targeting of an adenovirus serotype 5 (Ad5) vector deleted of CAR binding capability. Here, we assess in vivo transduction and biodistribution of Ad5 vectors with nonmodified fibers (Ad5) and a serotype 47 fiber-pseudotyped Ad5 (Ad5/47; subgroup D) virus following intravascular injection. Warfarin reduced liver transduction by both viruses. However, no impact on early liver virus accumulation was observed, suggesting no effect on Kupffer cell interactions. Hence, coagulation factors play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5 and Ad5/47 vectors.
Heterologous Prime/Boost Immunization of Rhesus Monkeys by Using Diverse Poxvirus Vectors
Authors: Santra Sampa , Sun Yue , Parvani Jenny G. , Philippon Valerie , Wyand Michael S. , Manson Kelledy , Gomez-Yafal Alicia , Mazzara Gail , Panicali Dennis , Markham Phillip D. , Montefiori David C. , Letvin Norman L.
Published: June 2007

As the diversity of potential immunogens increases within certain classes of vectors, the possibility has arisen of employing heterologous prime/boost immunizations using diverse members of the same family of vectors. The present study was initiated to explore the use of divergent pox vectors in a prime/boost regimen to elicit high-frequency cellular immune responses to human immunodeficiency virus type 1 envelope and simian immunodeficiency virus
gag
in rhesus monkeys. We demonstrated that monkeys vaccinated with a recombinant modified vaccinia virus Ankara (rMVA) prime/recombinant fowlpox virus (rFPV) boost regimen and monkeys vaccinated with a recombinant vaccinia virus prime/rFPV boost regimen developed comparable cellular immune responses that were greater in magnitude than those elicited by a homologous prime/boost with rMVA. Nevertheless, comparable magnitude recall cellular immune responses were observed in monkeys vaccinated with heterologous and homologous recombinant poxvirus following challenge with the CXCR4-tropic SHIV-89.6P. Consistent with this finding, comparable levels of containment of viral replication and CD4
+
T-lymphocyte preservation were seen in these groups of recombinant poxvirus-vaccinated monkeys. This study supports further exploration of combining recombinant vectors of the same family in prime/boost immunization strategies to optimize vaccine-elicited cellular immune responses.
Semliki Forest Virus Nonstructural Protein 2 Is Involved in Suppression of the Type I Interferon Response
Authors: Breakwell Lucy , Dosenovic Pia , Karlsson Hedestam Gunilla B. , D'Amato Mauro , Liljeström Peter , Fazakerley John , McInerney Gerald M.
Published: June 2007

The type I interferons (IFNs) are potent mediators of antiviral immunity, and many viruses have developed means to block their expression or their effects. Semliki Forest virus (SFV) infection induces rapid and profound silencing of host cell gene expression, a process believed to be important for the inhibition of the IFN response. In SFV-infected cells, a large proportion of the nonstructural protein nsp2 is found in the nucleus, but a role for this localization has not been described. In this work we demonstrate that a viral mutant, SFV4-RDR, in which the nuclear localization sequence of nsp2 has been rendered inactive, induces a significantly more robust IFN response in infected cells. This mutant virus replicates at a rate similar to that of the parental SFV4 strain and also shuts off host cell gene expression to similar levels, indicating that the general cellular shutoff is not responsible for the inhibition of IFN expression. Further, the rate of virus-induced nuclear translocation of early IFN transcription factors was not found to differ between the wild-type and mutant viruses, indicating that the effect of nsp2 is at a later stage. These results provide novel information about the mode of action of this viral IFN antagonist.
Na+-K+ pumps in the transverse tubular system of skeletal muscle fibers preferentially use ATP from glycolysis
Authors: Dutka T. L. , Lamb G. D.
Published: June 2007

The Na+-K+ pumps in the transverse tubular (T) system of a muscle fiber play a vital role keeping K+ concentration in the T-system sufficiently low during activity to prevent chronic depolarization and consequent loss of excitability. These Na+-K+ pumps are located in the triad junction, the key transduction zone controlling excitation-contraction (EC) coupling, a region rich in glycolytic enzymes and likely having high localized ATP usage and limited substrate diffusion. This study examined whether Na+-K+ pump function is dependent on ATP derived via the glycolytic pathway locally within the triad region. Single fibers from rat fast-twitch muscle were mechanically skinned, sealing off the T-system but retaining normal EC coupling. Intracellular composition was set by the bathing solution and action potentials (APs) triggered in the T-system, eliciting intracellular Ca2+ release and twitch and tetanic force responses. Conditions were selected such that increased Na+-K+ pump function could be detected from the consequent increase in T-system polarization and resultant faster rate of AP repriming. Na+-K+ pump function was not adequately supported by maintaining cytoplasmic ATP concentration at its normal resting level (∼8 mM), even with 10 or 40 mM creatine phosphate present. Addition of as little as 1 mM phospho(enol)pyruvate resulted in a marked increase in Na+-K+ pump function, supported by endogenous pyruvate kinase bound within the triad. These results demonstrate that the triad junction is a highly restricted microenvironment, where glycolytic resynthesis of ATP is critical to meet the high demand of the Na+-K+ pump and maintain muscle excitability.
A mechanistic approach to understanding conjugated linoleic acid's role in inflammation using murine models of rheumatoid arthritis
Authors: Butz Daniel E. , Li Guangming , Huebner Shane M. , Cook Mark E.
Published: June 2007

A naturally occurring fatty acid, conjugated linoleic acid (CLA), reduces immune-induced TNF and inducible cyclooxygenase (COX-2) expression; key mediators of inflammation in rheumatoid arthritis (RA). On the basis of previous work, it was hypothesized that dietary CLA would act as an anti-inflammatory agent in select animal models of RA. In the collagen antibody-induced arthritis (CAIA) model, mice fed CLA (mixed isomers of c9, t11, and t10, c12-CLA) for 3 wk before anticollagen antibody injection had reduced lipopolysaccharide-induced plasma TNF levels and had arthritic scores that were 60% of mice fed corn oil (CO). In the collagen-induced arthritis (CIA) model, mice fed mixed isomers of CLA for 21 days before immunization had lower IgG1titers, earlier signs of joint inflammation, but similar arthritis scores compared with CO fed mice during the remaining 70-day post-injection period. Beginning on day 80 to 133, CLA-fed mice had arthritic scores 70% that of the CO-fed mice. In a second CIA experiment, CLA was fed only after the booster injection. Plasma IgG1levels were not reduced and arthritis onset was delayed 4 days in CLA-fed mice compared with the CO-fed mice. Peak arthritis score was similar between CLA and CO-fed mice from day 35 to 56. Because CLA reduced inflammation in the CAIA model, delayed onset of arthritis in the CIA model (CIA experiment 2) and reduced arthritis score after day 80 in the CIA model (CIA experiment 1), we concluded that dietary CLA exhibited anti-inflammatory activity that was dependent on antibody.
Impact of α1-adrenoceptor expression on contractile properties of vascular smooth muscle cells
Authors: Gericke Adrian , Martinka Peter , Nazarenko Irina , Persson Pontus B. , Patzak Andreas
Published: June 2007

Low-frequency blood pressure oscillations (Mayer waves) are discussed as a marker for sympathetic modulation of vascular tone. However, the factors that determine the frequency response of the vasculature to sympathetic stimuli are not fully understood. Possible mechanisms include functions related to α1-adrenergic receptors (α1-AR) and postreceptor processes involved in the vascular contractile response. The purpose of the present study was to examine the hypothesis that expression levels of α1-AR and their subtype distribution determine velocity and magnitude of α1-AR-mediated vascular smooth muscle cell (VSMC) contraction. α1A-, α1B-, and α1D-AR subtypes were transfected into VSMCs from rat aorta and characterized immunocytochemically via confocal microscopy. Functional studies in isolated cells were performed using video microscopy. The α1-AR agonist phenylephrine produced dose-dependent contractions of VSMCs. All transfected groups were more sensitive to phenylephrine compared with controls. Maximal contraction velocity almost doubled in transfected cells. However, no differences in observed parameters were found between the three transfected groups. Contractile properties in response to membrane depolarization with KCl were similar in all groups. In conclusion, α1-AR density determines velocity and sensitivity of α1-AR-mediated contraction in VSMCs. α1-AR subtype distribution does not appear to influence vasoconstriction to sympathetic stimuli.
Diurnal protein expression in blood revealed by high throughput mass spectrometry proteomics and implications for translational medicine and body time of day
Authors: Martino Tami A. , Tata Nazneen , Bjarnason Georg A. , Straume Marty , Sole Michael J.
Published: June 2007

Molecular gene cycling is useful for determining body time of day (BTOD) with important applications in personalized medicine, including cardiovascular disease and cancer, our leading causes of death. However, it impractically requires repetitive invasive tissue sampling that is obviously not applicable for humans. Here we characterize diurnal protein cycling in blood using high-throughput proteomics; blood proteins are easily accessible, minimally invasive, and can importantly serve as surrogates for what is happening elsewhere in the body in health and disease. As proof of the concept, we used normal C57BL/6 mice maintained under regular 24-h light and dark cycles. First, we demonstrated fingerprint patterns in 24-h plasma, revealed using surface-enhanced laser desorption and ionization (SELDI). Second, we characterized diurnal cycling proteins in blood using chromatography and tandem electrospray ionization mass spectrometry. Importantly, we noted little association between the cycling blood proteome and tissue transcriptome, delineating the necessity to identify de novo cycling proteins in blood for measuring BTOD. Furthermore, we explored known interaction networks to identify putative functional pathways regulating protein expression patterns in blood, thus shedding new light on our understanding of integrative physiology. These studies have profound clinical significance in translating the concept of BTOD to the practical realm for molecular diagnostics and open new opportunities for clinically relevant discoveries when applied to ELISA-based molecular testing and/or point-of-care devices.
Profitability Analysis of Price-Taking Strategy in Disequilibrium
Authors: Huang Weihong
Published: June 2007

Conventional economic assumption that more sophistication in decision making is better than less is challenged with a profitability analysis conducted with an oligopolistic model consisting of a naive firm and a group of sophisticated firms. While the naive firm is assumed to adopt a simple Cobweb strategy by equating its marginal cost of current production to the last period's price, the sophisticated firms can take either individually or collusively any conventional sophisticated strategy such as Cournot and Stackelberg strategies. Contrary to the economic intuition, it is not the sophisticated firms but the naive firm who triumphs in equilibrium as well as during the dynamical transitionary periods, no matter what strategies the sophisticated firms may take. Moreover, when the economy turns cyclic or chaotic, a combination of the Cobweb strategy with a cautious adjustment strategy could also bring relative higher average profits for the naive firm than its rivals.
Web Content Search and Adaptation for IDTV: One Step Forward in the Mediamorphosis Process toward Personal-TV
Authors: Ferretti Stefano , Roccetti Marco , Palazzi Claudio E.
Published: June 2007

We are on the threshold of a mediamorphosis that will revolutionize the way we interact with our TV sets. The combination between interactive digital TV (IDTV) and the Web fosters the development of new interactive multimedia services enjoyable even through a TV screen and a remote control. Yet, several design constraints complicate the deployment of this new pattern of services. Prominent unresolved issues involve macro-problems such as collecting information on the Web based on users' preferences and appropriately presenting retrieved Web contents on the TV screen. To this aim, we propose a system able to dynamically convey contents from the Web to IDTV systems. Our system presents solutions both for personalized Web content search and automatic TV-format adaptation of retrieved documents. As we demonstrate through two case study applications, our system merges the best of IDTV and Web domains spinning the TV mediamorphosis toward the creation of the personal-TV concept.
Integer Powers of Arcsin
Authors: Borwein Jonathan M. , Chamberland Marc
Published: June 2007

New simple nested-sum representations for powers of the arcsin function are given. This generalization of Ramanujan's work makes connections to finite binomial sums and polylogarithms.
Characterization of the De Novo Biosynthetic Enzyme of Platelet Activating Factor, DDT-Insensitive Cholinephosphotransferase, of Human Mesangial Cells
Authors: Tsoupras Alexandros Basilios , Fragopoulou Elizabeth , Nomikos Tzortzis , Iatrou Christos , Antonopoulou Smaragdi , Demopoulos Constantinos Alexandros
Published: June 2007

Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT) of human mesangial cell (HMC), the main regulatory enzyme of PAFde novobiosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA), dithiothreitol (DTT), divalent cations (Mg2+and Ca2+), EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid) and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass “Dicentrarchuslabrax,” and gilthead sea bream “Sparus aurata”). The results indicated that the above compounds can influence PAF-CPT activity of HMC.
Rosiglitazone, an Agonist of PPARγ, Inhibits Non-Small Cell Carcinoma Cell Proliferation In Part through Activation of Tumor Sclerosis Complex-2
Authors: Han ShouWei , Zheng Ying , Roman Jesse
Published: June 2007

PPARγligands inhibit the proliferation of non-small cell lung carcinoma (NSCLC) cells in vitro. The mechanisms responsible for this effect remain incompletely elucidated, but PPARγligands appear to inhibit the mammalian target of rapamycin (mTOR) pathway. We set out to test the hypothesis that PPARγligands activate tuberous sclerosis complex-2 (TSC2), a tumor suppressor gene that inhibits mTOR signaling. We found that the PPARγligand rosiglitazone stimulated the phosphorylation of TSC2 at serine-1254, but not threonine-1462. However, an antagonist of PPARγand PPARγsiRNA did not inhibit these effects. Rosiglitazone also increased the phosphorylation of p38 MAPK, but inhibitors of p38 MAPK and its downstream signal MK2 had no effect on rosiglitazone-induced activation of TSC2. Activation of TSC2 resulted in downregulation of phosphorylated p70S6K, a downstream target of mTOR. A TSC2 siRNA induced p70S6K phosphorylation at baseline and inhibited p70S6K downregulation by rosiglitazone. When compared to a control siRNA in a thymidine incorporation assay, the TSC2 siRNA reduced the growth inhibitory effect of rosiglitazone by fifty percent. These observations suggest that rosiglitazone inhibits NSCLC growth partially through phosphorylation of TSC2 via PPARγ-independent pathways.
Hawaii Cohort Study of Serum Micronutrient Concentrations and Clearance of Incident Oncogenic Human Papillomavirus Infection of the Cervix
Authors: Goodman Marc T. , Shvetsov Yurii B. , McDuffie Katharine , Wilkens Lynne R. , Zhu Xuemei , Franke Adrian A. , Bertram Cathy Cramer , Kessel Bruce , Bernice Marge , Sunoo Christian , Ning Lily , Easa David , Killeen Jeffrey , Kamemoto Lori , Hernandez Brenda Y.
Published: June 2007

The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and β), total trans-lycopene and cis-lycopene, carotene (α, β, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (≤120 days). HPV clearance time was also significantly shorter among women with the highest compared with the lowest serum levels of α-tocopherol and total-tocopherol, but significant trends in these associations were limited to infections lasting ≤120 days. Clearance of persistent HPV infection (lasting >120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix. [Cancer Res 2007;67(12):5987–96]