bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility Study of an Intercooled-Cycle Marine Gas Turbine
Authors: Xue-you Wen , Dong-ming Xiao
Published: March 2008

From the perspective of an overall entity we analyzed the performance obtainable from the adoption of an intercooled-cycle gas turbine under different typical cycle parameters of a gas turbine. On this basis, a study was conducted of the conversion of a high-power simple-cycle marine gas turbine (MGT-33) into a type of intercooled-cycle marine gas turbine. The precondition of the conversion is to keep the flow path and the majority of the structure of the original engine gas generator unchanged in order to inherit the reliability of the prototype machine. The results of the study indicate that after the adoption of an intercooled cycle under the precondition of performing minimum structure modifications and maintaining the compactness of the engine as a whole, there is still a significant enhancement of the gas turbine overall performance with its power output and efficiency being increased by about 34% and 4.1%, respectively, demonstrating the merits of the engineering conversion under discussion.
New Steps to Improve Rotordynamic Stability Predictions of Centrifugal Compressors
Authors: Gupta Manoj K. , Soulas Thomas A. , Childs Dara W.
Published: March 2008

Improved rotordynamic stability is desired by end users, and centrifugal compressor manufacturers are expected to meet, if not exceed, this expectation. Compressor manufacturers are required to design and build machines that are rotordynamically stable on the test stand and in the field. Confidence has been established in predicting the excitation forces from seals and bearings, but impeller aerodynamic excitation forces continue to be a challenge. While much attention is paid to impellers from an aerodynamic performance point of view, more efforts are needed from a rotordynamic standpoint. A high-pressure, reinjection centrifugal compressor is analyzed in order to predict rotordynamic stability using the best available resources for seals and bearings. Impeller shroud forces are predicted using the bulk-flow model developed by Gupta and Childs (Gupta, M., and Childs, D., Proc. of ASME Turbo Expo 2000, Power for Land, Sea, and Air). Each impeller stage is analyzed and an attempt is made to improve the estimation of impeller aerodynamic excitation forces. Logarithmic decrement (log dec) predictions for the full rotor model consisting of all the stages and seals are compared to the full-load full-pressure test measured values using a magnetic bearing exciter. A good correlation is obtained between the measured test results and analytical predictions.
An Experimental Study of Effective Thermal Conductivity of High Temperature Insulations
Authors: Zhang Bo-ming , Xie Wei-hua , Du Shan-yi , Zhao Shu-yuan
Published: March 2008

An experimental apparatus was designed and fabricated to measure the effective thermal conductivities and simulate the temperature and pressure history of reentry of a launch vehicle into a planetary atmosphere with a maximum temperature of 1600°C. An improved testing method was used to test the thermal conductivities of an alumina fibrous insulation at environmental pressures from 0.03Pato105Pa with the average temperature of the sample increased to 864°C and its density being 128kg∕m3. A method based on temperature difference is used to compute the in-plane effective thermal conductivity, and the result shows that the in-plane thermal conductivity along the y axis is 1.47 times that along the x axis. The influences of temperature and pressure on the contribution of three heat transfer mechanisms to the effective thermal conductivities were compared.
Thermocapillary Convection in Floating Zones
Authors: Hu W. R. , Tang Z. M. , Li K.
Published: March 2008

This paper provides an overview of ongoing studies in the area of thermocapillary convection driven by a surface tension gradient parallel to the free surface in a floating zone. Here, research interests are focused around the onset of oscillatory thermocapillary convection, also known as the transition from quasisteady convection to oscillatory convection. The onset of oscillation depends on a set of critical parameters, and the margin relationship can be represented by a complex function of the critical parameters. The experimental results indicate that the velocity deviation of an oscillatory flow has the same order of magnitude as that of an average flow, and the deviations of other quantities, such as temperature and free surface radii fluctuations, are much smaller when compared with their normal counterparts. Therefore, the onset of oscillation should be a result of the dynamic process in a fluid, and the problem is a strongly nonlinear one. In the past few decades, several theoretical models have been introduced to tackle the problem using analytical methods, linear instability analysis methods, energy instability methods, and unsteady 3D numerical methods. The last of the above mentioned methods is known to be the most suitable for a thorough analysis of strong nonlinear processes, which generally leads to a better comparison with the experimental results. The transition from oscillatory thermocapillary convection to turbulence falls under the studies of chaotic behavior in a new system, which opens a fascinating new frontier in nonlinear science, a hot research area drawing many recent works. This paper reviews theoretical models and analysis, and also experimental research, on thermocapillary connection in floating zones. It cites 93 references.
Age and Evolution of the Grand Canyon Revealed by U-Pb Dating of Water Table-Type Speleothems
Authors: Polyak Victor , Hill Carol , Asmerom Yemane
Published: March 2008

The age and evolution of the Grand Canyon have been subjects of great interest and debate since its discovery. We found that cave mammillaries (water table indicator speleothems) from nine sites in the Grand Canyon showed uranium-lead dating evidence for an old western Grand Canyon on the assumption that groundwater table decline rates are equivalent to incision rates. Samples in the western Grand Canyon yielded apparent water table decline rates of 55 to 123 meters per million years over the past 17 million years, in contrast to eastern Grand Canyon samples that yielded much faster rates (166 to 411 meters per million years). Chronology and inferred incision data indicate that the Grand Canyon evolved via headward erosion from west to east, together with late-stage (∼3.7 million years ago) accelerated incision in the eastern block.
Response to Comment on "Early Archaean Microorganisms Preferred Elemental Sulfur, Not Sulfate"
Authors: Philippot Pascal , Van Zuilen Mark , Lepot Kevin , Thomazo Christophe , Farquhar James , Van Kranendonk Martin J.
Published: March 2008

Our knowledge of the sulfur cycle on early Earth is still in its infancy. Nevertheless, there exist enough geochemical constraints from the rock record to show that the theoretical mixing models proposed by Bao
et al
. are highly unlikely to account for the range of δ
34
S and Δ
33
S values recorded for the microscopic sulfides at the North Pole.
De Novo Computational Design of Retro-Aldol Enzymes
Authors: Jiang Lin , Althoff Eric A. , Clemente Fernando R. , Doyle Lindsey , Röthlisberger Daniela , Zanghellini Alexandre , Gallaher Jasmine L. , Betker Jamie L. , Tanaka Fujie , Barbas Carlos F. , Hilvert Donald , Houk Kendall N. , Stoddard Barry L. , Baker David
Published: March 2008

The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs that were experimentally characterized, 32, spanning a range of protein folds, had detectable retro-aldolase activity. Designs that used an explicit water molecule to mediate proton shuffling were significantly more successful, with rate accelerations of up to four orders of magnitude and multiple turnovers, than those involving charged side-chain networks. The atomic accuracy of the design process was confirmed by the x-ray crystal structure of active designs embedded in two protein scaffolds, both of which were nearly superimposable on the design model.
Antisocial Punishment Across Societies
Authors: Herrmann Benedikt , Thöni Christian , Gächter Simon
Published: March 2008

We document the widespread existence of antisocial punishment, that is, the sanctioning of people who behave prosocially. Our evidence comes from public goods experiments that we conducted in 16 comparable participant pools around the world. However, there is a huge cross-societal variation. Some participant pools punished the high contributors as much as they punished the low contributors, whereas in others people only punished low contributors. In some participant pools, antisocial punishment was strong enough to remove the cooperation-enhancing effect of punishment. We also show that weak norms of civic cooperation and the weakness of the rule of law in a country are significant predictors of antisocial punishment. Our results show that punishment opportunities are socially beneficial only if complemented by strong social norms of cooperation.
Coiled-Coil Irregularities and Instabilities in Group A
Streptococcus
M1 Are Required for Virulence
Authors: McNamara Case , Zinkernagel Annelies S. , Macheboeuf Pauline , Cunningham Madeleine W. , Nizet Victor , Ghosh Partho
Published: March 2008

Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A
Streptococcus
(GAS). Here, we report the ∼3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.
News from Avatar Editors
Authors: Hunter Dan
Published: March 2008

The Second Life Herald
. The Virtual Tabloid That Witnessed the Dawn of the Metaverse.
By Peter Ludlow and Mark Wallace
. MIT Press, Cambridge, MA, 2007. 311 pp. $29.95, £19.95. ISBN 9780262122948.

Drawing on Ludlow's experiences as a "virtual journalist," the authors explore such topics as conflicts between the owners and users of virtual worlds, among groups of users, and among individuals.
Improved Performance of Enzyme-Linked Immunosorbent Assays and the Effect of Human Immunodeficiency Virus Coinfection on the Serologic Detection of Herpes Simplex Virus Type 2 in Rakai, Uganda
Authors: Gamiel Jordyn L. , Tobian Aaron A. R. , Laeyendecker Oliver B. , Reynolds Steven J. , Morrow Rhoda Ashley , Serwadda David , Gray Ronald H. , Quinn Thomas C.
Published: March 2008

Ugandan subjects (820) were tested by Focus HerpeSelect enzyme-linked immunosorbent assay (ELISA), Kalon herpes simplex virus type 2 ELISA, and BioKit rapid test, and the results were compared to those of Western blotting. Higher-than-standard-index cutoff values gave optimal sensitivity and specificity. Kalon ELISA was the optimal assay when an index value of 1.5 was used (sensitivity, 91.7%; specificity, 92.4%).
Clinical Characteristics Associated with Isolation of Small-Colony Variants of
Staphylococcus aureus
and
Pseudomonas aeruginosa
from Respiratory Secretions of Patients with Cystic Fibrosis
Authors: Schneider Michael , Mühlemann Kathrin , Droz Sara , Couzinet Sabine , Casaulta Carmen , Zimmerli Stefan
Published: March 2008

During a 3-month period, small-colony variant phenotypes of both
Staphylococcus aureus
and
Pseudomonas aeruginosa
were isolated from respiratory secretions of 8.2% and 9.2%, respectively, of 98 patients with cystic fibrosis, particularly those with advanced pulmonary disease and prolonged antibiotic exposure.
Metallo-β-Lactamase Detection: Comparative Evaluation of Double-Disk Synergy versus Combined Disk Tests for IMP-, GIM-, SIM-, SPM-, or VIM-Producing Isolates
Authors: Picão Renata C. , Andrade Soraya S. , Nicoletti Adriana Gianinni , Campana Eloiza H. , Moraes Gabriela C. , Mendes Rodrigo E. , Gales Ana C.
Published: March 2008

The emergence of metallo-β-lactamase (MBL)-producing isolates is a challenge to routine microbiology laboratories, since there are no standardized methods for detecting such isolates. The aim of this study was to evaluate the accuracy of different phenotypic methods to detect MBL production among
Pseudomonas
spp.,
Acinetobacter
spp., and enterobacterial isolates, including GIM, IMP, SIM, SPM, and VIM variants. A total of 46 genetically unrelated
Pseudomonas aeruginosa
,
Pseudomonas putida
,
Acinetobacter
sp., and enterobacterial strains producing distinct MBLs were tested. Nineteen strains were included as negative controls. The inhibition of bacterial growth and β-lactam hydrolysis caused by MBL inhibitors (IMBL) also were evaluated. The isolates were tested for MBL production by both a double-disk synergy test (DDST) and a combined disk assay (CD) using imipenem and ceftazidime as substrates in combination with distinct IMBL. One hundred percent sensitivity and specificity were achieved by DDST using 2-mercaptopropionic acid in combination with ceftazidime and imipenem for the detection of MBL production among
P. aeruginosa
and
Acinetobacter
species isolates, respectively. The CD test showed the same results for detecting MBL-producing enterobacteria by combining imipenem and EDTA, with a 5.0-mm-breakpoint increase in the size of the inhibition zone. Our results indicate that both phenotypic methods to detect MBL-producing isolates should be based on the genera to be tested, regardless of the enzyme produced by such isolates, as well as on the local prevalence of MBL producers.
Evaluation of the NanoChip 400 System for Detection of Influenza A and B, Respiratory Syncytial, and Parainfluenza Viruses
Authors: Takahashi Hiroshi , Norman Sylvia A. , Mather Elizabeth L. , Patterson Bruce K.
Published: March 2008

The NanoChip400 system uses multiplex PCR chemistry and electronic microarray detection of influenza A and B viruses; respiratory syncytial viruses A and B; and human parainfluenza virus types 1, 2, and 3. The results obtained with the NanoChip 400 system were compared with those obtained by direct fluorescent-antibody staining (DFA) and real-time PCR with 122 and 130 specimens, respectively. Concordance between DFA and NanoChip 400 system was obtained for 106 of 122 (86.9%) specimens. On the basis of discrepancy analysis with specimens available for confirmatory real-time PCR testing, the sensitivity and specificity of the NanoChip 400 were 98.6% and 100%, respectively. With respect to specimens previously tested by real-time PCR, the NanoChip 400 system demonstrated a sensitivity of 91.1% and a specificity of 100%. The NanoChip 400 system provides clinical laboratories with a practical, rapid, and sensitive method for the detection of common respiratory viruses.
Immunoglobulin G Responses to a Panel of
Candida albicans
Antigens as Accurate and Early Markers for the Presence of Systemic Candidiasis
Authors: Clancy Cornelius J. , Nguyen Minh-Ly , Cheng Shaoji , Huang Hong , Fan Guixiang , Jaber Reia A. , Wingard John R. , Cline Christina , Nguyen M. Hong
Published: March 2008

Despite shortcomings, cultures of blood and sterile sites remain the “gold standard” for diagnosing systemic candidiasis. Alternative diagnostic markers, including antibody detection, have been developed, but none are widely accepted. In this study, we used an enzyme-linked immunosorbent assay to measure serum antibody responses against 15 recombinant
Candida albicans
antigens among 60 patients with systemic candidiasis due to various
Candida
spp. and 24 uninfected controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were significantly higher among patients with systemic candidiasis than among controls, whereas IgM responses were higher against only seven antigens. Using discriminant analysis that included IgG responses against the 15 antigens, we derived a mathematical prediction model that identified patients with systemic candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1, ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical correlation analyses performed as accurately as the full panel. Using the simplified model, we predicted systemic candidiasis in a separate test sample of 32 patients and controls with 100% sensitivity and 87.5% specificity. We also demonstrated that IgG titers against each of the four antigens included in the prediction model were significantly higher in convalescent-phase sera than in paired acute-phase sera. Taken together, our findings suggest that IgG responses against a panel of candidal antigens might represent an accurate and early marker of systemic candidiasis, a hypothesis that should be tested in future trials.
Alternative Algorithms for Human Immunodeficiency Virus Infection Diagnosis Using Tests That Are Licensed in the United States
Authors: Owen S. M. , Yang C. , Spira T. , Ou C. Y. , Pau C. P. , Parekh B. S. , Candal D. , Kuehl D. , Kennedy M. S. , Rudolph D. , Luo W. , Delatorre N. , Masciotra S. , Kalish M. L. , Cowart F. , Barnett T. , Lal R. , McDougal J. S.
Published: March 2008

Serodiagnosis of human immunodeficiency virus (HIV) infection in the United States has traditionally relied on a sequential two-test algorithm: an initial screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive specimens with a more specific supplemental test such as Western blotting or immunofluorescence. The supplemental tests are tedious, subjective, and expensive. In addition, there have been major improvements in the performance and accuracy of the EIA tests as well as the introduction of rapid serologic tests (RT) and HIV nucleic acid amplification tests (NAAT). Related to these improvements is the possibility that alternative algorithms using combinations of currently approved HIV tests may function as well as if not better than the current algorithm, with more flexibility, improved accuracy, and lower cost. To this end, we evaluated the performance of 12 currently licensed tests and 1 in-house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV-infected (
n
= 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (
n
= 513) people and of sequential specimens from people early in seroconversion (183 specimens from 15 patients). Test combinations were analyzed in two dual-test (sensitivity-optimized and specificity-optimized) algorithms and in a three-test (tie-breaking) algorithm, and performance was compared to the conventional algorithm. The results indicate that alternative algorithm strategies with currently licensed tests compare favorably with the conventional algorithm in detecting and confirming established HIV infection. Furthermore, there was a lower frequency of discordant or indeterminate results that require follow-up testing, and there was improved detection of early infection.
Evaluation of CDC-Recommended Approaches for Confirmatory Testing of Positive
Neisseria gonorrhoeae
Nucleic Acid Amplification Test Results
Authors: Moncada Jeanne , Donegan Elizabeth , Schachter Julius
Published: March 2008

We evaluated three of the CDC approaches for confirming
Neisseria gonorrhoeae
(gonococcus [GC])-positive nucleic acid amplification test (NAAT) results: (i) repeating the original test on the original specimen, (ii) testing the original specimen with a different test, and (iii) performing a different test on a duplicate specimen collected at the same visit. For the first approach, clinical specimens were initially tested by Aptima Combo 2 (AC2) (Gen-Probe Inc., San Diego, CA), ProbeTec (strand displacement amplification [SDA]) (Becton Dickinson Co., Sparks, MD), and Amplicor (PCR) (Roche Molecular Systems, Branchburg, NJ). The original GC-positive specimens were then retested by the same NAAT for confirmation. For the second approach, specimens initially positive by AC2, SDA, or PCR were retested by different NAATs (SDA, PCR, AC2, and Aptima
Neisseria gonorrhoeae
assay [AGC]; Gen-Probe Inc.). For the third approach, duplicate urethral swabs and first-catch urine (FCU) samples from men and duplicate cervical swabs and FCU samples from women were each tested by SDA, AC2, and AGC in parallel. We found that 89 to 96% of samples positive by SDA, PCR, and AC2 were confirmed by repeat testing and that 85 to 98% of SDA, PCR, and AC2 results were confirmed by using different NAATs on the original specimen. For FCU samples from men, any NAAT can be used for confirmation. However, for all other specimen types, some NAATs cannot be used to confirm positive results from other NAATs. Thus, a single repeat test appears to be a reliable method for confirmation, but by doing more extensive testing, an additional 5% were confirmed. With >90% of all GC-positive NAATs being confirmed, our results show that confirmatory testing is not warranted for these genital specimens.
Inability of Real-Time Reverse Transcriptase PCR Assay To Detect Subtype H7 Avian Influenza Viruses Isolated from Wild Birds
Authors: Xing Zheng , Cardona Carol , Dao Phuong , Crossley Beate , Hietala Sharon , Boyce Walter
Published: March 2008

We report a failure of the real-time reverse transcriptase PCR H7 subtyping protocol currently used in national avian influenza surveillance programs. Significant substitutions in primer and probe target sequences were identified, especially in wild bird viruses. The protocol, originally designed for detecting H7 influenza viruses in poultry, is not reliable for wild bird surveillance.
Pilot Study of Prevalence of High-Risk Human Papillomavirus Genotypes in Israeli Jewish Women Referred for Colposcopic Examination
Authors: Grisaru Dan , Avidor Boaz , Niv Jacob , Marmor Silvia , Almog Benjamin , Leibowitz Cecilia , Graidy Merav , Giladi Michael
Published: March 2008

The objective of the present study was to determine the prevalence of high-risk (HR) human papillomavirus (HPV) genotypes in a group of Israeli Jewish women referred for colposcopic examination. Scrape specimens were prospectively collected from 84 women referred for colposcopic examination. All the women underwent Papanicolaou (Pap) smears and colposcopies, and some also underwent cervical or loop electrosurgical excision procedure biopsy. HR HPV was detected in scrape specimens (Amplicor HPV test; Roche Molecular Systems), and the individual genotypes in these specimens were identified (HPV GenoArray test kit; Hybribio Ltd., Hong Kong). Forty-one (49%) specimens were positive by the Amplicor HPV test. Sixty-four samples (41 positive and 23 negative by the Amplicor HPV test) were also assayed by use of the HPV GenoArray kit. The overall level of agreement between the two assays was 93.8% (Cohen's kappa = 0.98). HR genotypes were found in 37/41 (90%) HPV-positive samples. The prevalences of the HR HPV genotypes in the 37 HPV-positive samples were 41% of patients for HPV type 16 (HPV-16), 22% for HPV-39, 19% for HPV-52, and 14% for HPV-18. Forty-one percent of these patients were infected with a single HR genotype, whereas 59% were infected with mixtures of HR genotypes. The presence of a relatively high percentage of HPV types 39 and 52 and the relatively high incidence of infections with mixtures of genotypes may be one of the reasons for the low rate of conversion from high-grade squamous intraepithelial lesions to invasive carcinoma in Israeli women. Larger and more comprehensive studies are warranted to investigate this issue in greater detail.
Nucleolin Is Required for an Efficient Herpes Simplex Virus Type 1 Infection
Authors: Callé Aleth , Ugrinova Iva , Epstein Alberto L. , Bouvet Philippe , Diaz Jean-Jacques , Greco Anna
Published: March 2008

Productive infection by herpes simplex virus type 1 (HSV-1), which occurs in the host cell nucleus, is accompanied by dramatic modifications of the nuclear architecture, including profound alterations of nucleolar morphology. Here, we show that the three most abundant nucleolar proteins—nucleolin, B23, and fibrillarin—are redistributed out of the nucleoli as a consequence of HSV-1 infection. We show that the amount of nucleolin increases progressively during the course of infection. We demonstrate for the first time that a nucleolar protein, i.e., nucleolin, colocalizes with ICP8 in the viral replication compartments, at the time when viral replication is effective, suggesting an involvement of nucleolin in the HSV-1 DNA replication process. At later times of infection, a granular form of nucleolin localizes to the cytoplasm, in structures that display the characteristic features of aggresomes, indicating that this form of nucleolin is very probably destined for degradation. The delocalization of nucleolin from the nucleoli requires the viral ICP4 protein or a factor(s) whose expression involves ICP4. Using small interfering RNA technology, we show that viral replication requires a high level of nucleolin expression, demonstrating for the first time a direct role for a nucleolar protein in herpes simplex virus biology.
Uniocular Anterior Chamber Inoculation of a Tumor Necrosis Factor Alpha-Expressing Recombinant of Herpes Simplex Virus Type 1 Results in More Rapid Destruction and Increased Viral Replication in the Retina of the Uninoculated Eye
Authors: Fields Mark A. , Zheng Mei , Wall Pam , Oberg Scott , Atherton Sally S.
Published: March 2008

Tumor necrosis factor alpha (TNF-α) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To determine whether overexpression of TNF-α affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-α constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-α recombinant, a recombinant containing the pCI plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the numbers and types of infiltrating inflammatory cells in the uninjected eyes. Virus titers were determined by plaque assay. There were no differences among the groups in virus titers or the route and timing of virus spread in the injected eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF-infected mice, TNF-α expression was increased and there were more viral antigen-positive cells and immune inflammatory cells. There was earlier microscopic evidence of retinal infection and destruction in these mice, and the titers of virus in the uninjected eyes were significantly increased in KOSTNF-infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6βrescue-, or KOS6β-infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF-α has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina of the uninoculated eye.
Genomic Analysis of Closely Related Astroviruses
Authors: Strain Errol , Kelley Laura A. , Schultz-Cherry Stacey , Muse Spencer V. , Koci Matthew D.
Published: March 2008

To understand astrovirus biology, it is essential to understand factors associated with its evolution. The current study reports the genomic sequences of nine novel turkey astrovirus (TAstV) type 2-like clinical isolates. This represents, to our knowledge, the largest genomic-length data set available for any one astrovirus type. The comparison of these TAstV sequences suggests that the TAstV species contains multiple subtypes and that recombination events have occurred across the astrovirus genome. In addition, the analysis of the capsid gene demonstrated evidence for both site-specific positive selection and purifying selection.
CD63 Is Not Required for Production of Infectious Human Immunodeficiency Virus Type 1 in Human Macrophages
Authors: Ruiz-Mateos Ezequiel , Pelchen-Matthews Annegret , Deneka Magdalena , Marsh Mark
Published: March 2008

During the assembly of human immunodeficiency virus type 1 (HIV-1) particles, the tetraspanin CD63 can be incorporated into the viral membrane. Indeed, cell surface tetraspanin microdomains that include CD63 have been proposed as sites for virus release. In addition, antibodies against CD63 can inhibit HIV infection of macrophages. In this cell type, HIV assembles into intracellularly sequestered plasma membrane domains that contain several other tetraspanins, including CD81, CD9, and CD53. CD63 is recruited to this domain following HIV infection. Together, these observations suggest that CD63 may have some function in the assembly of infectious virus particles and/or the infectivity of assembled virions. Here we have used RNA interference to knock down CD63 expression in monocyte-derived primary macrophages. We show that in the absence of CD63, HIV assembly is quantitatively comparable to that seen in CD63-expressing macrophages and that virus assembly occurs on compartments positive for CD81, CD9, and CD53. Moreover, the infectivity of macrophage-derived virus is unaffected by the loss of CD63. Together, our results indicate that at least in tissue culture, CD63 expression is not required for either the production or the infectivity of HIV-1.
Natural Selection for Nucleotide Usage at Synonymous and Nonsynonymous Sites in Influenza A Virus Genes
Authors: Kryazhimskiy Sergey , Bazykin Georgii A. , Dushoff Jonathan
Published: March 2008

Influenza A virus is one of the best-studied viruses and a model organism for the study of molecular evolution; in particular, much research has focused on detecting natural selection on influenza virus proteins. Here, we study the dynamics of the synonymous and nonsynonymous nucleotide composition of influenza A virus genes. In several genes, the nucleotide frequencies at synonymous positions drift away from the equilibria predicted from the synonymous substitution matrices. We investigate possible reasons for this unexpected behavior by fitting several regression models. Relaxation toward a mutation-selection equilibrium following a host jump fails to explain the dynamics of the synonymous nucleotide composition, even if we allow for slow temporal changes in the substitution matrix. Instead, we find that deep internal branches of the phylogeny show distinct patterns of nucleotide substitution and that these branches strongly influence the dynamics of nucleotide composition, suggesting that the observed trends are at least in part a result of natural selection acting on synonymous sites. Moreover, we find that the dynamics of the nucleotide composition at synonymous and nonsynonymous sites are highly correlated, providing evidence that even nonsynonymous sites can be influenced by selection pressure for nucleotide composition.
Murine Cytomegalovirus m38.5 Protein Inhibits Bax-Mediated Cell Death
Authors: Jurak Igor , Schumacher Uwe , Simic Hrvoje , Voigt Sebastian , Brune Wolfram
Published: March 2008

Many viruses encode proteins that inhibit the induction of programmed cell death at the mitochondrial checkpoint. Murine cytomegalovirus (MCMV) encodes the m38.5 protein, which localizes to mitochondria and protects human HeLa cells and fibroblasts from apoptosis triggered by proteasome inhibitors but not from Fas-induced apoptosis. However, the ability of this protein to suppress the apoptosis of murine cells and its role during MCMV infection have not been investigated previously. Here we show that m38.5 is expressed at early time points during MCMV infection. Cells infected with MCMVs lacking m38.5 showed increased sensitivity to cell death induced by staurosporine, MG132, or the viral infection itself compared to the sensitivity of cells infected with wild-type MCMV. This defect was eliminated when an m38.5 or Bcl-X
L
gene was inserted into the genome of a deletion mutant. Using fibroblasts deficient in the proapoptotic Bcl-2 family proteins Bak and/or Bax, we further demonstrated that m38.5 protected from Bax- but not Bak-mediated apoptosis and interacted with Bax in infected cells. These results consolidate the role of m38.5 as a viral mitochondrion-localized inhibitor of apoptosis and its functional similarity to the human cytomegalovirus UL37x1 gene product. Although the m38.5 gene is not homologous to the UL37x1 gene at the sequence level, m38.5 is conserved among rodent cytomegaloviruses. Moreover, the fact that MCMV-infected cells are protected from both Bak- and Bax-mediated cell death suggests that MCMV possesses an additional, as-yet-unidentified mechanism to block Bak-mediated apoptosis.
NEDD4L Overexpression Rescues the Release and Infectivity of Human Immunodeficiency Virus Type 1 Constructs Lacking PTAP and YPXL Late Domains
Authors: Chung Hyo-Young , Morita Eiji , von Schwedler Uta , Müller Barbara , Kräusslich Hans-Georg , Sundquist Wesley I.
Published: March 2008

The cellular ESCRT pathway functions in membrane remodeling events that accompany endosomal protein sorting, cytokinesis, and enveloped RNA virus budding. In the last case, short sequence motifs (termed late domains) within human immunodeficiency virus type 1 (HIV-1) p6
Gag
bind and recruit two ESCRT pathway proteins, TSG101 and ALIX, to facilitate virus budding. We now report that overexpression of the HECT ubiquitin E3 ligase, NEDD4L/NEDD4-2, stimulated the release of HIV-1 constructs that lacked TSG101- and ALIX-binding late domains, increasing infectious titers >20-fold. Furthermore, depletion of endogenous NEDD4L inhibited the release of these crippled viruses and led to cytokinesis defects. Stimulation of virus budding was dependent upon the ubiquitin ligase activity of NEDD4L and required only the minimal HIV-1 Gag assembly regions, demonstrating that Gag has ubiquitin-dependent,
cis
-acting late domain activities located outside of the p6 region. NEDD4L stimulation also required TSG101 and resulted in ubiquitylation of several ESCRT-I subunits, including TSG101. Finally, we found that TSG101/ESCRT-I was required for efficient release of Mason-Pfizer monkey virus, which buds primarily by using a PPXY late domain to recruit NEDD4-like proteins. These observations suggest that NEDD4L and possibly other NEDD4-like proteins can ubiquitylate and activate ESCRT-I to function in virus budding.
Efficient and Specific Rescue of Human Immunodeficiency Virus Type 1 Budding Defects by a Nedd4-Like Ubiquitin Ligase
Authors: Usami Yoshiko , Popov Sergei , Popova Elena , Göttlinger Heinrich G.
Published: March 2008

To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPx
n
L late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.
Digital Simulation of Cyclic Chronopotentiometry and Cyclic Reciprocal Derivative Chronopotentiometry for Linear Adsorption Systems
Authors: Fekner Zygmunt
Published: March 2008

Digital simulations were applied to generate potential-time response curves for cyclic chronopotentiometry under a constant current in order to gain insight into a reversible charge transfer process at a planar electrode under semi-infinite diffusion conditions. These simulations were carried out for two-species systems in which either both or just one component undergoes adsorption, and this process can be accurately described using the Henry isotherm. From the chronopotentiometric curves obtained, and following their numerical differentiation, the corresponding cyclic reciprocal derivative chronopotentiometric curves were generated and compared with the previously reported analytical solutions. The results obtained according to the proposed simulation scheme were shown to be in perfect agreement with the analytical solutions. It was also demonstrated that digital simulations are a powerful and versatile tool for studying and modeling two-species adsorption systems.
USING MULTIPLE PARADIGM RESEARCH METHODOLOGIES TO GAIN NEW INSIGHTS INTO ENTREPRENEURIAL MOTIVATIONS
Authors: KIRKWOOD JODYANNE , CAMPBELL-HUNT COLIN
Published: March 2008

Much of the extant entrepreneurship research has focused on studying the field using positivist research methodologies and little attention has been paid to interpretive methodologies or the use of multiple paradigms. The focus of the paper is on illustrating how we applied a multiple paradigm research methodology to an existing research problem. Specifically, the research was concerned with gender differences in motivations for becoming an entrepreneur. We explain how a multiple paradigm research methodology enabled us to gain new insights into an aspect of entrepreneurship where results of the prior research were not only contradictory, but also lacked a focus on theoretical development. Our research process involved two phases. First, a mail survey which was designed to replicate existing studies was administered to 289 entrepreneurs. The second phase involved in-depth face-to-face interviews with 50 entrepreneurs (25 men and 25 women) who responded to the mail survey. Theoretical contributions regarding entrepreneurial motivation are detailed, as are some more general implications of using multiple paradigm research methodologies in other entrepreneurship and organizational research.
OPPORTUNITIES AS EXISTING AND CREATED: A STUDY OF ENTREPRENEURS IN THE SWEDISH MOBILE INTERNET INDUSTRY
Authors: BERGLUND HENRIK
Published: March 2008

The notion of opportunities is fast becoming a central theme in the field of entrepreneurship research. As part of this growing interest, the ontological status of opportunities has been scrutinized with researchers tending to view them as either objectively existing or socially created. In the present treatment, this ontological debate is partly avoided in favor of a phenomenological examination of Mobile Internet entrepreneurs, which naturally bridges these distinctions. The empirical findings are used to propose a framework in which opportunities are seen as both existing and created in the evolving set of perceptions and projections, sometimes fixed and sometimes mutable, that provide the cognitive and practical drivers needed to guide entrepreneurial action.
FACILITATING PUBLIC SECTOR CORPORATE ENTREPRENEURSHIP PROCESS: A CONCEPTUAL MODEL
Authors: KEARNEY CLAUDINE , HISRICH ROBERT , ROCHE FRANK
Published: March 2008

The research to date in the literature has not provided a consensus on the nature of public entrepreneurship. Many authors relate the concept of entrepreneurship to only the private sector and dismiss the idea of public sector entrepreneurship. Others argue that the introduction of entrepreneurship into the public sector is inimical to its basic goals, concept and values. This paper proposes a conceptual model that explains the public sector corporate entrepreneurial process based on a review of past theoretical and empirical research. To date, very little research exists which attempts to establish a theoretical framework or model that illustrates the various components, including environmental and organizational characteristics, that effect the corporate entrepreneurship process within the public sector. The model is intended to depict key corporate entrepreneurial dimensions that relate to entrepreneurial behavior within the public sector organization. The proposed model delineates the antecedents and consequences of corporate entrepreneurship within the public sector.
BIVARIATE EXTENSION OF SOFTWARE RELIABILITY MODELING WITH NUMBER OF TEST CASES
Authors: ISHII TOMOTAKA , FUJIWARA TAKAJI , DOHI TADASHI
Published: March 2008

In this paper we consider a software reliability model (SRM) depending on the number of test cases executed in software testing. The resulting SRM is based on a two-dimensional discrete non-homogeneous Poisson process (NHPP) and is considered as a bivariate extension of the usual NHPP-based SRM by taking account of two time scales; calendar time and number of test cases executed. We apply the Marshall and Olkin's bivariate geometric distribution and develop a two-dimensional discrete geometric SRM. In a numerical example with real software fault data observed in four real development projects, we investigate the goodness-of-fit for the proposed SRM and refer to an applicability to the actual software reliability assessment.
A COMPONENT-ORIENTED RELIABILITY ASSESSMENT METHOD FOR OPEN SOURCE SOFTWARE
Authors: TAMURA YOSHINOBU , YAMADA SHIGERU
Published: March 2008

Software development environment has been changing into new development paradigms such as concurrent distributed development environment and the so-called open source project by using network computing technologies. Especially, an OSS (open source software) system which serves as key components of critical infrastructures in the society is still ever-expanding now. In case of considering the effect of the debugging process on an entire system in the development of a method of reliability assessment for the OSS, it is necessary to grasp the deeply-intertwined factors, such as programming path, size of each component, skill of fault reporter, and so on. In order to consider the effect of each software component on the reliability of an entire system, we propose a new approach to user-oriented software reliability assessment by creating a fusion of neural network and software reliability growth modeling. In this paper, we show application examples of component-oriented software reliability assessment based on neural network and software reliability growth modeling for the OSS. Also, we analyze actual software fault count data to show numerical examples of software reliability assessment for the OSS. Moreover, we develop the testing management tool for OSS.
BOOTSTRAP CONFIDENCE INTERVALS OF SOFTWARE RELIABILITY MEASURES BASED ON A GAMMA FUNCTION MODEL
Authors: KIMURA MITSUHIRO
Published: March 2008

This paper focuses on the generalization of several software reliability models and the derivation of confidence intervals of reliability assessment measures. First we propose a gamma function model as a generalized model, and discuss how to obtain the confidence intervals from a data set by using a bootstrap scheme when the size of the data set is small. A two-parameter numerical differentiation method is applied to the data set to estimate the model parameters. We also show several numerical illustrations of software reliability assessment.
AN ANALYTICAL APPROACH TO THE SAFETY OF ROAD NETWORKS
Authors: ZIO ENRICO , SANSAVINI GIOVANNI , MAJA ROBERTO , MARCHIONNI GIOVANNA
Published: March 2008

In this paper, recently introduced topological measures of interconnection and efficiency of network systems are applied to the safety analysis of the road transport system of the Province of Piacenza in Italy.

The vulnerability of the network is evaluated with respect to the loss of a road link, e.g. due to a car accident, road work or other jamming occurrences. Eventually, the improvement in the global and local safety indicators following the implementation of a road development plan is evaluated.
A BSDE APPROACH TO THE SKOROKHOD EMBEDDING PROBLEM FOR THE BROWNIAN MOTION WITH DRIFT
Authors: ANKIRCHNER STEFAN , HEYNE GREGOR , IMKELLER PETER
Published: March 2008

We solve Skorokhod's embedding problem for Brownian motion with linear drift (Wt + κ t)t≥0 by means of techniques of stochastic control theory. The search for a stopping time T such that the law of WT + κ T coincides with a prescribed law μ possessing the first moment is based on solutions of backward stochastic differential equations of quadratic type. This new approach generalizes an approach by Bass [3] of the classical version of Skorokhod's embedding problem using martingale representation techniques.
METASTABILITY FOR RANDOM PERTURBATIONS OF NEARLY-HAMILTONIAN SYSTEMS
Authors: ATHREYA AVANTI , FREIDLIN MARK
Published: March 2008

We characterize the phenomenon of metastability for a small random perturbation of a nearly-Hamiltonian dynamical system. We use the averaging principle and the theory of large deviations to prove that the metastable "state" is, in general, not a single state but rather a nondegenerate probability measure across the stable equilibrium points of the unperturbed Hamiltonian system. The set of all possible "metastable distributions" is a finite set that is independent of the stochastic perturbation.
RECURRENCE OF SELF-REPELLING AND SELF-ATTRACTING WALKS ON THE PRE-SIERPIŃSKI GASKET AND ℤ
Authors: DENKER MANFRED , HATTORI KUMIKO
Published: March 2008

We prove recurrence of self-repelling and self-attracting walks on the pre-Sierpiński gasket and ℤ. We also determine a set of parameters for which this walk defines infinite, σ-finite and ergodic measure preserving dynamical systems.
LARGE DEVIATION ASYMPTOTICS FOR CONTINUED FRACTION EXPANSIONS
Authors: KESSEBÖHMER MARC , SLASSI MEHDI
Published: March 2008

We study large deviation asymptotics for processes defined in terms of continued fraction digits. We use the continued fraction digit sum process to define a stopping time and derive a joint large deviation asymptotic for the upper and lower fluctuation processes. Also a large deviation asymptotic for single digits is given.
PROBABILISTIC ASPECTS OF EXTREME EVENTS GENERATED BY PERIODIC AND QUASIPERIODIC DETERMINISTIC DYNAMICS
Authors: NICOLIS G. , BALAKRISHNAN V. , NICOLIS C.
Published: March 2008

We consider the distribution of the maximum for finite, deterministic, periodic and quasiperiodic sequences, and contrast the extreme value distributions in these cases with the classical results for iidrv's. A significant feature in the case of deterministic sequences is a multi-step structure for the distribution function. The extreme value distribution for the circle map with an irrational parameter is obtained in closed form with the help of the three-gap theorem for the map Xj+1 = (Xj + a) mod 1 where a ∈ (0,1) is an irrational number.
THE DISTRIBUTION OF DISTANCES BETWEEN RANDOMLY CONSTRUCTED GENOMES: GENERATING FUNCTION, EXPECTATION, VARIANCE AND LIMITS
Authors: XU WEI
Published: March 2008

Based on a large repertoire of chromosomal rearrangement operations, the genomic distance d between two genomes with χr and χb linear chromosomes, respectively, both containing the same (or orthologous) n genes or markers, is d = n + max (χr,χb) - c, where c is the number of cycles in the breakpoint graph of the two genomes. In this paper, we study the exact probability distribution of c. We derive the expectation and variance, and show that, in the limit, the expectation of d is [Formula: see text].