bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of an Experimental Model To Test the Efficacy of Planned Exposure to Live Porcine Reproductive and Respiratory Syndrome Virus
Authors: Opriessnig Tanja , Baker Rodney B. , Halbur Patrick G.
Published: October 2007

The objectives of this study were to test the efficacy and safety of planned exposure to porcine reproductive and respiratory syndrome virus (PRRSV) in protecting naïve and previously exposed pigs against PRRSV challenge and to gain information on the dose of PRRSV necessary to induce a protective immune response. Fifty 2-week-old pigs were randomly assigned to one of five groups: a group exposed to a low dose of autogenous PRRSV vaccine (the L-VAC group), a group exposed to a high dose of autogenous vaccine (the H-VAC group), a group exposed to a low dose of a heterologous PRRSV strain (strain SDSU73) prior to planned exposure (the SDSU73-L-VAC group), a group exposed to a high dose of a heterologous PRRSV strain (strain SDSU73) prior to planned exposure (the SDSU73-H-VAC group), and a control group. All groups were challenged with PRRSV VR2385 5 weeks after the planned exposure. Necropsy was done 2 weeks after the PRRSV challenge. The H-VAC, SDSU73-L-VAC, and SDSU73-H-VAC groups had significantly (P< 0.05) less severe clinical disease (sneezing, respiratory scores, and weight gain), significantly (P< 0.05) less severe macroscopic and microscopic lung lesions, and significantly (P< 0.05) lower numbers of PRRSV genomic copy numbers in their sera compared to the results for the control group. Planned exposure to live PRRSV can be used as an inexpensive and effective way to decrease the severity of PRRSV-induced disease following subsequent challenge.
Evaluation of a Multiplexed PCR Assay for Detection of Respiratory Viral Pathogens in a Public Health Laboratory Setting
Authors: Marshall David J. , Reisdorf Erik , Harms Gerda , Beaty Edward , Moser Michael J. , Lee Wai-Ming , Gern James E. , Nolte Frederick S. , Shult Pete , Prudent James R.
Published: October 2007

There are numerous viral and bacterial causes of respiratory disease. To enable rapid and sensitive detection of even the most prevalent causes, there is a need for more-simplified testing systems that enable researchers and clinicians to perform multiplexed molecular diagnostics quickly and easily. To this end, a new multiplexed molecular test called the MultiCode-PLx respiratory virus panel (PLx-RVP) was developed and then implemented in a public health laboratory setting. A total of 687 respiratory samples were analyzed for the presence of 17 viruses that commonly cause respiratory disease. As a comparator, the samples were also tested using a standard testing algorithm that included the use of a real-time influenza virus A and B reverse transcription-PCR test and routine viral culture identification. The standard testing algorithm identified 503 (73%) samples as positive and 184 as negative. Analyzing the same 687 samples, the PLx-RVP assay detected one or more targets in 528 (77%) samples and found 159 samples negative for all targets. There were 25 discordant results between the two systems; 14 samples were positive for viruses not routinely tested for by the Wisconsin State Laboratory of Hygiene, and 13 of these were confirmed by real-time PCR. When the results of the standard testing algorithm were considered “true positives,” the PLx-RVP assay showed an overall sensitivity of 99% and an overall specificity of 87%. In total, the PLx-RVP assay detected an additional 40 viral infections, of which 11 were mixed infections.
Genotypic and Phenotypic Analysis of
Enterobacter sakazakii
Strains from an Outbreak Resulting in Fatalities in a Neonatal Intensive Care Unit in France
Authors: Caubilla-Barron J. , Hurrell E. , Townsend S. , Cheetham P. , Loc-Carrillo C. , Fayet O. , Prère M.-F. , Forsythe S. J.
Published: October 2007

In 1994, an outbreak of
Enterobacter sakazakii
infections occurred in a neonatal intensive care unit in France from 5 May to 11 July. During the outbreak, 13 neonates were infected with
E. sakazakii
, resulting in 3 deaths. In addition, four symptomless neonates were colonized by
E. sakazakii
. The strains were subjected to 16S rRNA gene sequence analysis, genotyped using pulsed-field gel electrophoresis, and phenotyped for a range of enzyme activities.
E. sakazakii
was isolated from various anatomical sites, reconstituted formula, and an unopened can of powdered infant formula. A fourth neonate died from septic shock, attributed to
E. sakazakii
infection, during this period. However, 16S rRNA gene sequence analysis revealed that the organism was
Enterobacter cloacae
. There were three pulsotypes of
E. sakazakii
associated with infected neonates, and three neonates were infected by more than one genotype. One genotype matched isolates from unused prepared formula and unfinished formula. However, no pulsotypes matched the
E. sakazakii
strain recovered from an unopened can of powdered infant formula. One pulsotype was associated with the three fatal cases, and two of these isolates had extended-spectrum β-lactamase activity. It is possible that
E. sakazakii
strains differ in their pathogenicities, as shown by the range of symptoms associated with each pulsotype.
Isolation and Characterization of a Novel Helicobacter Species, “
Helicobacter macacae
,” from Rhesus Monkeys with and without Chronic Idiopathic Colitis
Authors: Fox James G. , Boutin Samuel R. , Handt Laurence K. , Taylor Nancy S. , Xu Shilu , Rickman Barry , Marini Robert P. , Dewhirst Floyd E. , Paster Bruce J. , Motzel Sherri , Klein Hilton J.
Published: October 2007

Chronic idiopathic colitis is a common clinical entity in young captive rhesus monkeys. Eight isolates, cultured from five monkeys in colony 1 with endemic diarrhea and three from colony 2 without diarrhea, were grown under microaerobic conditions on selective agar and were classified by full 16S rRNA sequence, biochemical, and phenotypic analysis as a novel helicobacter, “
Helicobacter macacae
” (proposed name). All eight strains of
H. macacae
had 99.5% identical 16S rRNA sequences.
Comparison of Microsatellite Length Polymorphism and Multilocus Sequence Typing for DNA-Based Typing of
Candida albicans
Authors: Garcia-Hermoso Dea , Cabaret Odile , Lecellier Gael , Desnos-Ollivier Marie , Hoinard Damien , Raoux Dorothée , Costa Jean-Marc , Dromer Françoise , Bretagne Stéphane
Published: October 2007

For genotyping
Candida albicans
isolates, two PCR-based methods have recently emerged: multilocus sequence typing (MLST), based on the sequence of selected genes, and microsatellite length polymorphism (MLP), based on the length of PCR products containing variable numbers of short DNA repeats. To compare the two methods in their abilities to differentiate and group
C. albicans
isolates, we selected 50 independent isolates collected at the National Reference Center for Mycoses and Antifungals. MLST typing was performed using sequencing of seven loci as described at
http://test1.mlst.net
. The MLP method consisted of a single multiplex PCR testing three different loci. Dendrograms were constructed by the unweighted pair group cluster method with Euclidean metric for both methods. The correlation between the distance matrices was performed with a Mantel test tested with 1,000 random permutations. The sensitivity and specificity of the MLP typing system were determined after allocating MLST groups for the greater number of isolates of each distinct MLP group. The discriminatory power index was >0.99, and the distances between the isolates were highly correlated with both systems. The Mantel coefficient and the Pearson product-moment correlation coefficient were 35,699 and 0.32, respectively (
P
≤ 1.2 × 10
−6
). Using MLP, the average specificity and sensitivity of clustering compared to MLST were 83% and 73%, respectively, when the singletons were excluded. The two methods are similarly discriminatory and can be interchangeable depending on the objectives. MLP is less expensive and faster than MLST. However, MLST is currently more accurate and additional standardization is needed for MLP.
Canine Parvovirus Types 2c and 2b Circulating in North American Dogs in 2006 and 2007
Authors: Kapil Sanjay , Cooper Emily , Lamm Cathy , Murray Brandy , Rezabek Grant , Johnston Larry , Campbell Gregory , Johnson Bill
Published: October 2007

Parvovirus is the most common viral cause of diarrhea in young puppies. Based on the analysis of a partial VP2 sequence of 54 samples, canine parvovirus type 2c (CPV-2c) (
n
= 26), CPV-2b (
n
= 25), and CPV-2 (
n
= 3) were detected in the United States. The American CPV-2b isolates have unique codons (494 and 572) in VP2.
Population-Based Molecular Epidemiological Study of Tuberculosis in Malatya, Turkey
Authors: Durmaz Riza , Zozio Thierry , Gunal Selami , Allix Caroline , Fauville-Dufaux Maryse , Rastogi Nalin
Published: October 2007

This investigation describes drug resistance patterns and genotyping data on a total of 145Mycobacterium tuberculosisstrains isolated between 2000 and 2004 in Malatya, Turkey. Drug susceptibility results indicated a total of 20% resistant and 4.8% of multidrug-resistant isolates. Spoligotyping resulted in 25 unique patterns and 120 strains in 19 clusters (2 to 33 strains per cluster). When the results were compared to an international spoligotyping database, 19 of 25 unique patterns matched existing shared spoligotype international types (SITs). This led to the description of 38 SITs with 139 strains and 6 orphan patterns (not previously reported). Five of the SITs (SIT759, SIT1936, SIT1937, SIT1938, and SIT2285) were newly created. The most prevalent spoligotype was SIT41 (LAM7-TUR) with 33 (23.9%) isolates. The repartition of strains according to majorM. tuberculosisclades (in decreasing order) was as follows: ill-defined T clade (45.7%) > Latin American and Mediterranean (LAM; 29%) > Haarlem (15.9%). Strains belonging to Central Asian (CAS), East-African Indian (EAI), Beijing, and Africanum clades were absent in this setting. IS6110-restriction fragment length polymorphism (RFLP) resulted in 19 clusters (52 strains), with a final clustering rate of 35.9% and a recent transmission rate of 22.8%. Typing based on mycobacterial interspersed repetitive units (MIRUs) permitted us to identify 65 patterns (23 orphan patterns and 42 patterns that matched existing MIRU international types in an updated database). The combination of the three typing methods allowed us to calculate a final clustering rate of 22% and a significantly lower transmission rate of 13.1%. The discrimination achieved by IS6110-RFLP/MIRUs was not significantly improved by adding spoligotyping results (1.4%). We conclude that our patient population is infected by diverseM. tuberculosispopulations; however, the majority of the ongoing transmission is due to “evolutionary recent” tuberculosis lineages belonging to principal genetic group 2 (PGG2; Haarlem and LAM) and PGG3 (ill-defined T clade), and most of it is attributable to the LAM7-TUR sublineage with an enhanced phylogeographical specificity for Turkey. An absence of lineages belonging to PGG1 clones (EAI, CAS, and Beijing, essentially found in Central, South, and Southeast Asia), is noteworthy.
Norovirus Infections in Symptomatic and Asymptomatic Food Handlers in Japan
Authors: Ozawa Kazuhiro , Oka Tomoichiro , Takeda Naokazu , Hansman Grant S.
Published: October 2007

Noroviruses are the leading cause of outbreaks of gastroenteritis in the world. At present, norovirus genogroup II, genotype 4 (GII/4), strains are the most prevalent in many countries. In this study we investigated 55 outbreaks and 35 sporadic cases of norovirus-associated gastroenteritis in food handlers in food-catering settings between 10 November 2005 and 9 December 2006 in Japan. Stool specimens were collected from both symptomatic and asymptomatic individuals and were examined for norovirus by real-time reverse transcription-PCR; the results were then confirmed by sequence analysis. Norovirus was detected in 449 of 2,376 (19%) specimens. Four genogroup I (GI) genotypes and 12 GII genotypes, including one new GII genotype, were detected. The GII/4 sequences were predominant, accounting for 19 of 55 (35%) outbreaks and 16 of 35 (46%) sporadic cases. Our results also showed that a large number of asymptomatic food handlers were infected with norovirus GII/4 strains. Norovirus GII had a slightly higher mean viral load (1 log unit higher) than norovirus GI, i.e., 3.81 × 10
8
versus 2.79 × 10
7
copies/g of stool. Among norovirus GI strains, GI/4 had the highest mean viral load, whereas among GII strains, GII/4 had the highest mean viral load (2.02 × 10
8
and 7.96 × 10
9
copies/g of stool, respectively). Importantly, we found that asymptomatic individuals had mean viral loads similar to those of symptomatic individuals, which may account for the increased number of infections and the predominance of an asymptomatic transmission route.
Cavitary Disease and Quantitative Sputum Bacillary Load in Cases of Pulmonary Tuberculosis
Authors: Palaci Moises , Dietze Reynaldo , Hadad David Jamil , Ribeiro Fabiola Karla Corrêa , Peres Renata Lyrio , Vinhas Solange Alves , Maciel Ethel Leonor Noia , do Valle Dettoni Valdério , Horter Libby , Boom W. Henry , Johnson John L. , Eisenach Kathleen D.
Published: October 2007

We examined sputum bacterial loads in adults with newly diagnosed tuberculosis using quantitative culture and time-until-positive (DTP) culture in BACTEC 460. Patients with cavitary disease had higher CFU levels than those without cavities and shorter DTPs. Within radiographic strata of moderately and far advanced tuberculosis, higher CFU counts were associated with cavitary disease.
The Zinc Finger Antiviral Protein Acts Synergistically with an Interferon-Induced Factor for Maximal Activity against Alphaviruses
Authors: MacDonald Margaret R. , Machlin Erica S. , Albin Owen R. , Levy David E.
Published: October 2007

Type I interferons (IFNs) signal through specific receptors to mediate expression of genes, which together confer a cellular antiviral state. Overexpression of the zinc finger antiviral protein (ZAP) imparts a cellular antiviral state againstRetroviridae,Togaviridae, andFiloviridaevirus family members. Since ZAP expression is induced by IFN, we utilized Sindbis virus (SINV) to investigate the role of other IFN-induced factors in ZAP's inhibitory potential. Overexpressed ZAP did not inhibit virion production or SINV-induced cell death in BHK cells deficient in IFN production (and thus IFN signaling), suggesting a role for an IFN-induced factor in ZAP's activity. IFN pretreatment in the presence of ZAP resulted in greater inhibition than IFN alone. Using mouse embryo fibroblast (MEF) cells deficient in Stat1, we showed that signaling through the IFN receptor is necessary for IFN′s enhancement of ZAP activity. Unlike in BHK cells, however, overexpressed ZAP exhibited antiviral activity in the absence of IFN. In wild-type MEFs with an intact Stat1 gene, IFN pretreatment synergized with ZAP to generate a potent antiviral response. Despite failing to inhibit SINV virion production and virus-induced cell death in BHK cells, ZAP inhibited translation of the incoming viral RNA. IFN pretreatment synergized with ZAP to further block protein expression from the incoming viral genome. We further show that silencing of IFN-induced ZAP reduces IFN efficacy. Our findings demonstrate that ZAP can synergize with another IFN-induced factor(s) for maximal antiviral activity and that ZAP's intrinsic antiviral activity on virion production and cell survival can have cell-type-specific outcomes.
Identification of Novel Antipoxviral Agents: Mitoxantrone Inhibits Vaccinia Virus Replication by Blocking Virion Assembly
Authors: Deng Liang , Dai Peihong , Ciro Anthony , Smee Donald F. , Djaballah Hakim , Shuman Stewart
Published: October 2007

The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely target of the drug. Whole-genome sequencing of mitoxantrone-resistant viruses pinpointed missense mutations in the N-terminal domain of vaccinia DNA ligase. Despite its favorable activity in cell culture, mitoxantrone administered intraperitoneally at the maximum tolerated dose failed to protect mice against a lethal intranasal infection with vaccinia virus.
Nef-Mediated Enhancement of Virion Infectivity and Stimulation of Viral Replication Are Fundamental Properties of Primate Lentiviruses
Authors: Münch Jan , Rajan Devi , Schindler Michael , Specht Anke , Rücker Elke , Novembre Francis J. , Nerrienet Eric , Müller-Trutwin Michaela C. , Peeters Martine , Hahn Beatrice H. , Kirchhoff Frank
Published: October 2007

Nef is a multifunctional accessory protein of primate lentiviruses. Recently, it has been shown that the ability of Nef to downmodulate CD4, CD28, and class I major histocompatibility complex is highly conserved between most or all primate lentiviruses, whereas Nef-mediated downregulation of T-cell receptor-CD3 was lost in the lineage that gave rise to human immunodeficiency virus type 1 (HIV-1). Whether or not other Nef activities are preserved between different groups of primate lentiviruses remained to be determined. Here, we show thatnefgenes from a large variety of HIVs and simian immunodeficiency viruses (SIVs) enhance virion infectivity and stimulate viral replication in human cells and/or in ex vivo infected human lymphoid tissue (HLT). Notably,nefalleles from unpassaged SIVcpz and SIVsmm enhanced viral infectivity, replication, and cytopathicity in cell culture and in ex vivo infected HLT as efficiently as those from HIV-1 and HIV-2, their human counterparts. Furthermore,nefgenes from several highly divergent SIVs that have not been found in humans were also highly active in human cells and/or tissues. Thus, most primate lentiviral Nefs enhance virion infectivity and stimulate viral replication. Moreover, our data show that SIVcpz and SIVsmm Nefs do not require adaptive changes to perform these functions in human cells or tissues and support the idea thatnefalleles from other primate lentiviruses would also be capable of promoting efficient virus spread in humans.
A Protective and Broadly Cross-Neutralizing Epitope of Human Papillomavirus L2
Authors: Gambhira Ratish , Karanam Balasubramanyam , Jagu Subhashini , Roberts Jeffrey N. , Buck Christopher B. , Bossis Ioannis , Alphs Hannah , Culp Timothy , Christensen Neil D. , Roden Richard B. S.
Published: October 2007

We generated a monoclonal antibody, RG-1, that binds to highly conserved L2 residues 17 to 36 and neutralizes human papillomavirus 16 (HPV16) and HPV18. Passive immunotherapy with RG-1 was protective in mice. Antiserum to the HPV16 L2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses HPV5, HPV6, HPV16, HPV 18, HPV31, HPV 45, HPV 52, HPV 58, bovine papillomavirus 1, and HPV11 native virions. Depletion of HPV16 L2 peptide 17-36-reactive antibodies from cross-neutralizing rabbit and human L2-specific sera abolished cross-neutralization and drastically reduced neutralization of the cognate type. This cross-neutralization of diverse HPVs associated with cervical cancer, genital warts, and
epidermodysplasia verruciformis
suggests the possibility of a broadly protective, peptide-based vaccine.
Proteolysis of the Ebola Virus Glycoproteins Enhances Virus Binding and Infectivity
Authors: Kaletsky Rachel L. , Simmons Graham , Bates Paul
Published: October 2007

Cellular cathepsins are required for Ebola virus infection and are believed to proteolytically process the Ebola virus glycoprotein (GP) during entry. However, the significance of cathepsin cleavage during infection remains unclear. Here we demonstrate a role for cathepsin L (CatL) cleavage of Ebola virus GP in the generation of a stable 18-kDa GP1 viral intermediate that exhibits increased binding to and infectivity for susceptible cell targets. Cell binding to a lymphocyte line was increased when CatL-proteolysed pseudovirions were used, but lymphocytes remained resistant to Ebola virus GP-mediated infection. Genetic removal of the highly glycosylated mucin domain in Ebola virus GP resulted in cell binding similar to that observed with CatL-treated full-length GP, and no overall enhancement of binding or infectivity was observed when mucin-deleted virions were treated with CatL. These results suggest that cathepsin cleavage of Ebola virus GP facilitates an interaction with a cellular receptor(s) and that removal of the mucin domain may facilitate receptor binding. The influence of CatL in Ebola virus GP receptor binding should be useful in future studies characterizing the mechanism of Ebola virus entry.
Double-Labeled Rabies Virus: Live Tracking of Enveloped Virus Transport
Authors: Klingen Yvonne , Conzelmann Karl-Klaus , Finke Stefan
Published: October 2007

Here we describe a strategy to fluorescently label the envelope of rabies virus (RV), of the
Rhabdoviridae
family, in order to track the transport of single enveloped viruses in living cells. Red fluorescent proteins (tm-RFP) were engineered to comprise the N-terminal signal sequence and C-terminal transmembrane spanning and cytoplasmic domain sequences of the RV glycoprotein (G). Two variants of tm-RFP were transported to and anchored in the cell surface membrane, independent of glycosylation. As shown by confocal microscopy, tm-RFP colocalized at the cell surface with the RV matrix and G protein and was incorporated into G gene-deficient virus particles. Recombinant RV expressing the membrane-anchored tm-RFP in addition to G yielded infectious viruses with mosaic envelopes containing both tm-RFP and G. Viable double-labeled virus particles comprising a red fluorescent envelope and a green fluorescent ribonucleoprotein were generated by expressing in addition an enhanced green fluorescent protein-phosphoprotein fusion construct (S. Finke, K. Brzozka, and K. K. Conzelmann, J. Virol. 78:12333-12343, 2004). Individual enveloped virus particles were observed under live cell conditions as extracellular particles and inside endosomal vesicles. Importantly, double-labeled RVs were transported in the retrograde direction over long distances in neurites of in vitro-differentiated NS20Y neuroblastoma cells. This indicates that the typical retrograde axonal transport of RV to the central nervous system involves neuronal transport vesicles in which complete enveloped RV particles are carried as a cargo.
Preserved Central Memory and Activated Effector Memory CD4+T-Cell Subsets in Human Immunodeficiency Virus Controllers: an ANRS EP36 Study
Authors: Potter Simon J. , Lacabaratz Christine , Lambotte Olivier , Perez-Patrigeon Santiago , Vingert Benoît , Sinet Martine , Colle Jean-Hervé , Urrutia Alejandra , Scott-Algara Daniel , Boufassa Faroudy , Delfraissy Jean-François , Thèze Jacques , Venet Alain , Chakrabarti Lisa A.
Published: October 2007

Human immunodeficiency virus (HIV) controllers are rare individuals who spontaneously control HIV type 1 replication for 10 years or more in the absence of antiretroviral treatment. In the present study, HIV controllers (n= 11) maintained potent HIV-specific CD4 responses in spite of very low antigenic loads. Their CD4+central memory T (TCM) cells were characterized by near-normal numbers and preserved interleukin-2 (IL-2) secretion in response to HIV antigens and uniformly high expression of the survival receptor IL-7 receptor α (IL-7Rα). Controllers expressed CCR7 at higher levels than uninfected controls, suggesting differences in TCM-cell homing patterns. CD4+effector memory T (TEM)-cell responses were polyfunctional in HIV controllers, while IL-2 secretion was lost in viremic patients. Cytokine production was three times higher in controllers than in treated patients with undetectable viral loads, suggesting an intrinsically more efficient response in the former group. The total CD4+TEM-cell pool underwent immune activation in controllers, as indicated by increased HLA-DR expression, decreased IL-7Rα expression, a bias towards gamma interferon production upon polyclonal stimulation, and increased macrophage inflammatory protein 1β secretion associated with chronic CCR5 down-regulation. Thus, HIV controllers showed a preserved CD4+TCM-cell compartment and signs of potent functional activation in the CD4+TEM-cell compartment. While controllers did not show the generalized immune activation pattern associated with disease progression, they had signs of immune activation restricted to the effector compartment. These findings suggest the induction of an efficient, nondetrimental type of immune activation in patients who spontaneously control HIV.
Herpes Simplex Virus Type 2 Glycoprotein G Is Targeted by the Sulfated Oligo- and Polysaccharide Inhibitors of Virus Attachment to Cells
Authors: Adamiak Beata , Ekblad Maria , Bergström Tomas , Ferro Vito , Trybala Edward
Published: October 2007

Variants of herpes simplex virus type 2 (HSV-2) generated by virus passage in GMK-AH1 cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to PI-88 in their initial infection of cells and/or their cell-to-cell spread. The major alteration detected in all variants resistant to PI-88 in the initial infection of cells was a frameshift mutation(s) in the glycoprotein G (gG) gene that resulted in the lack of protein expression. Molecular transfer of the altered gG gene into the wild-type background confirmed that the gG-deficient recombinants were resistant to PI-88. In addition to PI-88, all gG-deficient variants of HSV-2 were resistant to the sulfated polysaccharide heparin. The gG-deficient virions were capable of attaching to cells, and this activity was relatively resistant to PI-88. In addition to having a drug-resistant phenotype, the gG-deficient variants were inefficiently released from infected cells. Purified gG bound to heparin and showed the cell-binding activity which was inhibited by PI-88. Many PI-88 variants produced syncytia in cultured cells and contained alterations in gB, including the syncytium-inducing L792P amino acid substitution. Although this phenotype can enhance the lateral spread of HSV in cells, it conferred no virus resistance to PI-88. Some PI-88 variants also contained occasional alterations in gC, gD, gE, gK, and UL24. In conclusion, we found that glycoprotein gG, a mucin-like component of the HSV-2 envelope, was targeted by sulfated oligo- and polysaccharides. This is a novel finding that suggests the involvement of HSV-2 gG in interactions with sulfated polysaccharides, including cell surface glycosaminoglycans.
X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation to KSHV Reactivation from Latency
Authors: Wilson Sam J. , Tsao Edward H. , Webb Benjamin L. J. , Ye Hongtao , Dalton-Griffin Lucy , Tsantoulas Christoforos , Gale Catherine V. , Du Ming-Qing , Whitehouse Adrian , Kellam Paul
Published: October 2007

Reactivation of lytic replication from viral latency is a defining property of all herpesviruses. Despite this, the authentic physiological cues for the latent-lytic switch are unclear. Such cues should ensure that viral lytic replication occurs under physiological conditions, predominantly in sites which facilitate transmission to permissive uninfected cells and new susceptible hosts. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with the B-cell neoplasm primary effusion lymphoma (PEL), in which the virus remains latent. We have previously shown that PEL cells have the gene expression profile and immunophenotype of cycling preplasma cells (plasmablasts). Here, we show that the highly active spliced isoform of plasma cell transcription factor X box binding protein 1 (XBP-1s) is a lytic switch for KSHV. XBP-1s is normally absent in PEL, but the induction of endoplasmic reticulum stress leads to XBP-1s generation, plasma cell-like differentiation, and lytic reactivation of KSHV. XBP-1s binds to and activates the KSHV immediate-early gene ORF50 and synergizes with the ORF50 gene product RTA to induce a full lytic cycle. These data suggest that KSHV remains latent until B-cell terminal differentiation into plasma cells, the transcriptional environment of which provides the physiological “lytic switch” through XBP-1s. This links B-cell terminal differentiation to KSHV lytic reactivation.
A Novel Zinc-Binding Domain Is Essential for Formation of the Functional Junín Virus Envelope Glycoprotein Complex
Authors: York Joanne , Nunberg Jack H.
Published: October 2007

The envelope glycoprotein of the Junín arenavirus (GP-C) mediates entry into target cells through a pH-dependent membrane fusion mechanism. Unlike other class I viral fusion proteins, the mature GP-C complex retains a cleaved, 58-amino-acid signal peptide (SSP) as an essential subunit, required both for trafficking of GP-C to the cell surface and for the activation of membrane fusion. SSP has been shown to associate noncovalently in GP-C via the cytoplasmic domain (CTD) of the transmembrane fusion subunit G2. In this report we investigate the molecular basis for this intersubunit interaction. We identify an invariant series of six cysteine and histidine residues in the CTD of G2 that is essential for incorporation of SSP in the GP-C complex. Moreover, we show that a CTD peptide fragment containing His-447, His-449, and Cys-455 specifically binds Zn
2+
at subnanomolar concentrations. Together, these results suggest a zinc finger-like domain structure in the CTD of G2. We propose that the remaining residues in the series (His-459, Cys-467, and Cys-469) form an intersubunit zinc-binding center that incorporates Cys-57 of SSP. This unusual motif may act to retain SSP in the GP-C complex and position the ectodomain loop of SSP for its role in modulating membrane fusion activity. The unique tripartite organization of GP-C could provide novel molecular targets for therapeutic intervention in arenaviral disease.
Type I Interferons Are Essential in Controlling Neurotropic Coronavirus Infection Irrespective of Functional CD8 T Cells
Authors: Ireland Derek D. C. , Stohlman Stephen A. , Hinton David R. , Atkinson Roscoe , Bergmann Cornelia C.
Published: October 2007

Neurotropic coronavirus infection induces expression of both beta interferon (IFN-β) RNA and protein in the infected rodent central nervous system (CNS). However, the relative contributions of type I IFN (IFN-I) to direct, cell-type-specific virus control or CD8 T-cell-mediated effectors in the CNS are unclear. IFN-I receptor-deficient (IFNAR−/−) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both succumbed to infection within 9 days. Compared to wild-type (wt) mice, replication was prominently increased in all glial cell types and spread to neurons, demonstrating expanded cell tropism. Furthermore, increased pathogenesis was associated with significantly enhanced accumulation of neutrophils, tumor necrosis factor alpha, interleukin-6, chemokine (C-C motif) ligand 2, and IFN-γ within the CNS. The absence of IFN-I signaling did not impair induction or recruitment of virus-specific CD8 T cells, the primary adaptive mediators of virus clearance in wt mice. Despite similar IFN-γ-mediated major histocompatibility complex class II upregulation on microglia in infected IFNAR−/−mice, class I expression was reduced compared to that on microglia in wt mice, suggesting a synergistic role of IFN-I and IFN-γ in optimizing class I antigen presentation. These data demonstrate a critical direct antiviral role of IFN-I in controlling virus dissemination within the CNS, even in the presence of potent cellular immune responses. By limiting early viral replication and tropism, IFN-I controls the balance of viral replication and immune control in favor of CD8 T-cell-mediated protective functions.
The Rabies Virus Glycoprotein Receptor p75
NTR
Is Not Essential for Rabies Virus Infection
Authors: Tuffereau Christine , Schmidt Klaus , Langevin Christelle , Lafay Florence , Dechant Georg , Koltzenburg Martin
Published: October 2007

Rabies virus glycoprotein (RVG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75
NTR
), through its cysteine-rich domain 1, is a specific receptor for RVG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75
NTR
in RV infection of primary neurons. We show that RV infects around 20% of DRG neurons, of which more than 80% are p75
NTR
positive, have large diameters, and are capsaicin insensitive. Surprisingly, RV binding and infection are absent in about half of the p75
NTR
-expressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75
NTR
is not sufficient to mediate RV interaction in sensory neurons. The rate and specificity of neural infection are unchanged in RV-infected p75
NTRExonIV−/−
mice that lack all extracellular receptor domains and in wild-type mice infected with two independent RV mutants that lack p75
NTR
binding. Accordingly, the mortality rate is unchanged in the absence of RV-p75
NTR
interaction. We conclude that although p75
NTR
is a receptor for soluble RVG in transfected cells of heterologous expression systems, an RVG-p75
NTR
interaction is not necessary for RV infection of primary neurons. This means that other receptors are required to mediate RV infection in vivo and in vitro.
Testing the performance of a forest ecosystem model (FORECAST) against 29 years of field data in aPseudotsuga menziesiiplantation
Authors: Blanco Juan A. , Seely Brad , Welham Clive , Kimmins J. P. (Hamish) , Seebacher Tanya M.
Published: October 2007

The ability of the forest ecosystem management model FORECAST to project a 29-year record of stand response to factorial thinning and fertilization treatments in a Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco) plantation at Shawnigan Lake (Vancouver Island, British Columbia, Canada) was assessed. Model performance was evaluated firstly using for calibration a regional data set and secondly with site-specific data from control plots. Model output was compared against field measurements of height, diameter, stem density, component biomass (aboveground), and litterfall rates and estimates of nutrient uptake, foliar N efficiency, and understory vegetation biomass. When calibrated with regional data, results from graphical comparisons, three measures of goodness-of-fit, and equivalence testing demonstrated that FORECAST can produce predictions of good to moderate accuracy depending on the variable of interest. Model performance was generally better when compared with field measurements (e.g., top height, diameter at breast height, and stem density) as opposed to outputs derived from allometric and volume equations. Use of site-specific data to calibrate the model always improved performance, although improvements were modest for most variables, with the exception of branch and foliage biomass. The benefits of site-specific calibration, however, should be weighed against the costs of obtaining such data. The intended use of the model will likely determine the level of effort expended in its calibration.
Linking forests and economic well-being: a four-quadrant approach
Authors: Wang Sen , DesRoches C. Tyler , Sun Lili , Stennes Brad , Wilson Bill , Cornelis van Kooten   G.
Published: October 2007

This paper has three main objectives: (i) to investigate whether the four-quadrant approach introduced by     J.S. Maini reveals a useful typology for grouping countries by gross domestic product (GDP) and forest cover per capita, (ii) to determine if the framework can enhance our understanding of the relationship between forest cover and GDP per capita, and (iii) to investigate why countries in the four-quadrant world occupy different quadrants and to determine the principal factors affecting country movement across and within the individual quadrants. The examination reveals that countries can be classified into four broad categories and that GDP and forest cover per capita have a low but consistent level of negative association. After regressing economic, institutional, social capital, and other variables on a country’s occupancy and movement in the four-quadrant world, the results suggest that countries in each quadrant share different characteristics and that factors underlying country movement vary according to the quadrant being observed. Overall, countries with less corruption and higher education are likely to experience increases in both forest cover and GDP per capita, while countries exporting a significant proportion of forest products have a reduced probability of increasing both variables.
Wind-driven gap development in Birkley Wood, a long-term retention of planted Sitka spruce in upland Britain
Authors: Quine C.P. , Malcolm D. C.
Published: October 2007

Management of planted forests in Britain is changing to incorporate biodiversity and other nontimber values by lengthening rotations, seeking alternatives to clear-felling, and identifying stands for nonintervention. However, there are particular uncertainties over stand development of exotic species on areas of high windthrow hazard. This study considered the effect of strong winds between 1987 and 2000 on stand development of Sitka spruce ( Picea sitchensis (Bong.) Carrière) planted in 1923. Windthrown gap area increased eightfold through at least 38 separate events. Windthrow of trees assessed as stable occurred during periods of higher wind speed than those with windthrow of trees assessed as vulnerable, and there was a nonlinear relationship between wind speed and increase in gap area. Gap expansion contributed more to the increase in gap area than new gap formation, and the centre of the largest gap migrated downwind. Nevertheless, a substantial proportion of the stand remains undisturbed to an extent not predicted. Therefore, a complex stand structure may develop, including a partial wave of natural regeneration of Sitka spruce in the expanding gaps, but species diversification will be slow due to the absence of local seed sources. The results provide insights for stand dynamics in windy, maritime environments.
Ground-layer response to group selection with legacy-tree retention in a managed northern hardwood forest
Authors: Shields Joshua M. , Webster Christopher R.
Published: October 2007

We examined the effects of group selection with legacy-tree retention on ground-layer or understory diversity and composition in an uneven-aged northern hardwood forest in the Upper Peninsula of Michigan. We sampled 20 reference plots in the surrounding forest matrix and 49 openings with radii of 0.5 (n = 16), 0.75 (n = 17), and 1.0 (n = 16) times mean canopy tree height (22 m). Resultant opening areas were 321 ± 16 (mean ± SEs), 697 ± 21, and 1256 ± 39 m2, respectively. Each opening contained a centrally located legacy tree. Two years after harvesting, ground-layer diversity was significantly higher in openings than on reference plots (p < 0.05) because of an influx of early seral, wetland, and weedy exotic species. The importance of aggressive ruderals (i.e., Carex ormostachya Wieg. and Rubus idaeus subsp. strigosus (Michx.) Focke) increased significantly (p < 0.001) with increasing opening area. Although the importance and cover of several late-seral species were lower in openings compared with the forest matrix, few species found in the matrix were wholly absent from the openings. These results suggest that ground-layer plant communities in managed northern hardwood forests may display a high degree of resilience to intermediate-intensity disturbances.
SEMI-REGULAR MASAS OF TRANSFINITE LENGTH
Authors: WHITE STUART A. , WIGGINS ALAN D.
Published: October 2007

In 1965, Tauer produced a countably infinite family of semi-regular masas in the hyperfinite II 1 factor, no pair of which are conjugate by an automorphism. This was achieved by iterating the process of passing to the algebra generated by the normalizers and, for each n ∈ ℕ, finding masas for which this procedure terminates at the nth stage. Such masas are said to have length n. In this paper, we consider a transfinite version of this idea, giving rise to a notion of ordinal valued length. We show that all countable ordinals arise as lengths of semi-regular masas in the hyperfinite II 1 factor. Furthermore, building on work of Jones and Popa, we obtain all possible combinations of regular inclusions of irreducible subfactors in the normalizing tower.
CHEN–RUAN COHOMOLOGY OF ADE SINGULARITIES
Authors: PERRONI FABIO
Published: October 2007

We study Ruan's cohomological crepant resolution conjecture [41] for orbifolds with transversal ADE singularities. In the An-case, we compute both the Chen–Ruan cohomology ring [Formula: see text] and the quantum corrected cohomology ring H*(Z)(q1,…,qn). The former is achieved in general, the later up to some additional, technical assumptions. We construct an explicit isomorphism between [Formula: see text] and H*(Z)(-1) in the A1-case, verifying Ruan's conjecture. In the An-case, the family H*(Z)(q1,…,qn) is not defined for q1 = ⋯ = qn = -1. This implies that the conjecture should be slightly modified. We propose a new conjecture in the An-case (Conjecture 1.9). Finally, we prove Conjecture 1.9 in the A2-case by constructing an explicit isomorphism.
PILOT-AIDED MULTIUSER CHANNEL ESTIMATION AND TRACKING IN MIMO-OFDM SYSTEMS
Authors: YANG QINGHAI , KWAK KYUNG SUP
Published: October 2007

This paper addresses the pilot-aided multiuser least square (LS) channel estimation for the uplink of multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing (OFDM) systems. The systems under consideration allow all users use all available subcarriers independently and thus involve multiuser interference in the frequency domain. Direct application of the known pilot-aided single-user channel estimation methods to these systems is prohibited, requiring much more new investigations. The decentralized and centralized channel estimation algorithms are developed according to different multiuser scenarios. Optimal multiuser pilots are proposed, especially for centralized estimation methods with respect to the mean square error (MSE) of LS channel estimate. In addition, channel tracking algorithms are represented in terms of individual user's channels.
A GENERALIZED ABFT TECHNIQUE USING A FAULT TOLERANT NEURAL NETWORK
Authors: NIA AMIR MOOSAVIE , MOHAMMADI KARIM
Published: October 2007

In this paper, a measure of sensitivity is defined to evaluate fault tolerance of neural networks and we show that the sensitivity of a link is closely related to the amount of information passed through it. Based on this assumption, we prove that the distribution of output error caused by s-a-0 (stuck at 0) faults in an MLP network has a Gaussian distribution function. UDBP (Uniformly Distributed Back Propagation) algorithm is then introduced to minimize mean and variance of the output error. Then an MLP neural network trained with UDBP, contributes in an Algorithm-Based Fault Tolerant (ABFT) scheme to protect a nonlinear data process block. A systematic real convolution code guarantees that faults representing errors in the processed data will result in notable nonzero values in syndrome sequence. A majority logic decoder can now easily detect and correct single faults by observing the syndrome sequence. Simulation results demonstrating the error detection and correction behavior against random s-a-0 faults are presented too.
FAST RESIDUE-TO-BINARY CONVERSION USING BASE EXTENSION AND THE CHINESE REMAINDER THEOREM
Authors: OMONDI AMOS R.
Published: October 2007

Residue number systems are attractive due to their basic arithmetic operations, such as addition and multiplication, are carry-free; this facilitates low-power, high-speed implementations. But converting from residue to conventional notation is generally problematic. In this paper, we propose a high-speed architecture for reverse conversion; this is based on Base Extension and the Chinese Remainder Theorem.
WATT MATTERS MOST? DESIGN SPACE EXPLORATION OF HIGH-PERFORMANCE MICROPROCESSORS FOR POWER-PERFORMANCE EFFICIENCY
Authors: TRANCOSO PEDRO
Published: October 2007

Computer systems have evolved significantly in the last years leading to high-performance systems. This, however, has come with a cost of large power dissipation. As such, power-awareness has become a major factor in processor design. Therefore, it is important to have a complete understanding of the power and performance behavior of all processor components. In order to achieve this, the current work presents a comprehensive analysis of power-performance efficiency for different high-end microarchitecture configurations using three different workloads: multimedia, scientific, and database. The objectives of this work are: (1) to analyze and compare the power-performance efficiency for different workloads; (2) to present a sensitivity analysis for the microarchitecture parameters in order to identify which ones are more sensitive to changes in terms of power-performance efficiency; and (3) to propose power-performance efficient configurations for each workload.

The simulation results show that the multimedia workload is the one achieving the highest efficiency but the database workload is the most sensitive to parameter changes. In addition, the results also show that the parameter sensitivity depends significantly on the workload. While the issue width and clock frequency present very high sensitivity across all workloads (approximately 100%), for the database workload, the first-level instruction cache size shows an even higher sensitivity (149%). The correct configuration of these microarchitecture parameters is essential. A careless configuration of a single parameter from a baseline setup may result in a loss of the power-performance efficiency of up to 99%. Finally, carefully tuning multiple parameters simultaneously may result in gains up to 154% over the power-performance efficiency of the baseline configuration.
LOW-POWER EIGHT-BIT SCSDL CLA WITH A NOVEL SPLIT-LEVEL CHARGE-SHARING DIFFERENTIAL LOGIC (SCSDL)
Authors: CHANG ROBERT C. , LIN HSIN-LEI , WANG I-HAO
Published: October 2007

A novel logic family, called Split-Level Charge-Sharing Differential Logic (SCSDL), is proposed in this letter. The SCSDL uses the charge recycling technique to reduce power dissipation of differential logic in the precharge phase. The simulation results show that the SCSDL has the best power-delay product compared to several other differential logic families. An eight-bit carry lookahead adder (CLA) designed using the proposed SCSDL can reduce at least 30.64% of power-delay product compared to DCVSL CLA dissipation. A test chip was fabricated to illustrate the feasibility of the SCSDL circuit.
A NOVEL VISION-BASED FINGER-WRITING CHARACTER RECOGNITION SYSTEM
Authors: JIN LIANWEN , YANG DUANDUAN , ZHEN LI-XIN , HUANG JIAN-CHENG
Published: October 2007

A novel video-based finger writing virtual character recognition system (FVCRS) is described in this paper. With this FVCR system, one can enter characters into a computer by just using the movement of fingertip, without any additional device such as a keyboard or a digital pen. This provides a new wireless character-inputting method. A simple but effective background model is built for segmenting human-finger movements from cluttered background. A robust fingertip detection algorithm based on feature matching is given, and recognition of the finger-writing character is by a DTW-based classifier. Experiments show that the FVCRS can successfully recognize finger-writing uppercase and lowercase English alphabet with the accuracy of 95.3% and 98.7%, respectively.