bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Chaperone-Activated Nonenveloped Virus Perforates the Physiologically Relevant Endoplasmic Reticulum Membrane
Authors: Rainey-Barger Emily K. , Magnuson Brian , Tsai Billy 
Published: September 2007

ABSTRACT
The nonenveloped polyomavirus (Py) traffics from the plasma membrane to the endoplasmic reticulum (ER), where it penetrates the ER membrane, allowing the viral genome to reach the nucleus to cause infection. The mechanism of membrane penetration for Py, and for other nonenveloped viruses, remains poorly characterized. We showed previously that the ER chaperone ERp29 alters the conformation of Py coat protein VP1, enabling the virus to interact with membranes. Here, we developed a membrane perforation assay and showed that the ERp29-activated Py perforates the physiologically relevant ER membrane, an event that likely initiates viral penetration. Biochemical analysis revealed that the internal protein VP2 is exposed in the activated viral particle. Accordingly, we demonstrate that VP2 binds to, integrates into, and perforates the ER membrane; the other internal protein, VP3, binds to and integrates into the ER membrane but is not sufficient for perforation. Our data thus link the activity of a cellular factor on a nonenveloped virus to the membrane perforation event and identify a viral component that mediates this process.
Humanized NOD/SCID/IL2RγnullMice Transplanted with Hematopoietic Stem Cells under Nonmyeloablative Conditions Show Prolonged Life Spans and Allow Detailed Analysis of Human Immunodeficiency Virus Type 1 Pathogenesis
Authors: Watanabe Satoru , Ohta Shinrai , Yajima Misako , Terashima Kazuo , Ito Mamoru , Mugishima Hideo , Fujiwara Shigeyoshi , Shimizu Kazufumi , Honda Mitsuo , Shimizu Norio , Yamamoto Naoki 
Published: September 2007

ABSTRACTIn a previous study, we demonstrated that humanized NOD/SCID/IL2Rγnull(hNOG) mice constructed with human hematopoietic stem cells (HSCs) allow efficient human immunodeficiency virus type 1 (HIV-1) infection. However, HIV-1 infection could be monitored for only 43 days in the animals due to their short life spans. By transplanting HSCs without any myeloablation methods, the mice successfully survived longer than 300 days with stable engraftment of human cells. The mice showed high viremia state for more than the 3 months examined, with systemic HIV-1 infection and gradual decrease of CD4+T cells analogous to that in humans. These capacities of the hNOG mice are very attractive for modeling mechanisms of AIDS progression and therapeutic strategy.
Cell Culture Adaptation of Hepatitis C Virus and In Vivo Viability of an Adapted Variant
Authors: Kaul Artur , Woerz Ilka , Meuleman Philip , Leroux-Roels Geert , Bartenschlager Ralf 
Published: September 2007

ABSTRACTProduction of infectious hepatitis C virus in cell culture has become possible because of the unique properties of the JFH1 isolate. However, virus titers are rather low, limiting the utility of this system. Here we describe the generation of cell culture-adapted JFH1 variants yielding higher titers of infectious particles and enhanced spread of infection in cultured cells. Sequence analysis of adapted genomes revealed a complex pattern of mutations that differed in two independent experiments. Adaptive mutations were observed both in the structural and in the nonstructural regions, with the latter having the highest impact on enhancement of virus titers. The major adaptive mutation was identified in NS5A, and it enhanced titers of three intergenotypic chimeras consisting of the structural region of a genotype 1a, 1b, or 3a isolate and the remainder of the JFH1 isolate. The mutation resides at the P3 position of the NS5A-B cleavage site and slows down processing, implying that subtle differences in replication complex formation appear to determine the efficiency of virus formation. Highly adapted JFH1 viruses carrying six mutations established a robust infection in uPA-transgenic SCID mice xenografted with human hepatocytes. However, the mutation in NS5A which enhanced virus titers in cell culture the most had reverted to wild type in nearly half of the viral genomes isolated from these animals at 15 weeks postinoculation. These results argue for some level of impaired fitness of this mutant in vivo.
Epitope Determinants of a Chimpanzee Dengue Virus Type 4 (DENV-4)-Neutralizing Antibody and Protection against DENV-4 Challenge in Mice and Rhesus Monkeys by Passively Transferred Humanized Antibody
Authors: Lai Ching-Juh , Goncalvez Ana P. , Men Ruhe , Wernly Claire , Donau Olivia , Engle Ronald E. , Purcell Robert H. 
Published: September 2007

ABSTRACTThe chimpanzee monoclonal antibody (MAb) 5H2 is specific for dengue virus type 4 (DENV-4) and neutralizes the virus at a high titer in vitro. The epitope detected by the antibody was mapped by sequencing neutralization escape variants of the virus. One variant contained a Lys174-Glu substitution and another contained a Pro176-Leu substitution in domain I of the DENV-4 envelope protein (E). These mutations reduced binding affinity for the antibody 18- to >100-fold. Humanized immunoglobulin G (IgG) 5H2, originally produced from an expression vector, has been shown to be a variant containing a nine-amino-acid deletion in the Fc region which completely ablates antibody-dependent enhancement of DENV replication in vitro. The variant MAb, termed IgG 5H2 ΔD, is particularly attractive for exploring its protective capacity in vivo. Passive transfer of IgG 5H2 ΔD at 20 μg/mouse afforded 50% protection of suckling mice against challenge with 25 50% lethal doses of mouse neurovirulent DENV-4 strain H241. Passive transfer of antibody to monkeys was conducted to demonstrate proof of concept for protection against DENV challenge. Monkeys that received 2 mg/kg of body weight of IgG 5H2 ΔD were completely protected against 100 50% monkey infectious doses (MID50) of DENV-4, as indicated by the absence of viremia and seroconversion. A DENV-4 escape mutant that contained a Lys174-Glu substitution identical to that found in vitro was isolated from monkeys challenged with 106MID50of DENV-4. This substitution was also present in all naturally occurring isolates belonging to DENV-4 genotype III. These studies have important implications for possible antibody-mediated prevention of DENV infection.
Association of Nef with p21-Activated Kinase 2 Is Dispensable for Efficient Human Immunodeficiency Virus Type 1 Replication and Cytopathicity in Ex Vivo-Infected Human Lymphoid Tissue
Authors: Schindler Michael , Rajan Devi , Specht Anke , Ritter Carolin , Pulkkinen Kati , Saksela Kalle , Kirchhoff Frank 
Published: September 2007

ABSTRACT

Interaction of the human immunodeficiency virus type 1 (HIV-1) Nef protein with p21-activated kinase 2 (PAK2) has been proposed to play a role in T-cell activation, viral replication, apoptosis, and progression to AIDS. However, these hypotheses were based on results obtained using Nef mutants impaired in multiple functions. Recently, it was reported that Nef residue F191 is specifically involved in PAK2 binding. However, only a limited number of Nef activities were investigated in these studies. To further evaluate the role of F191 in Nef function and to elucidate the biological relevance of Nef-PAK2 interaction, we performed a comprehensive analysis of HIV-1 Nef mutants carrying F191H and F191R mutations. We found that the F191H mutation reduces and the F191R mutation disrupts the association of Nef with PAK2. Both mutants upregulated the major histocompatibility complex II (MHC-II)-associated invariant chain and downregulated CD4, MHC-I, and CD28, although with reduced efficiency for the latter. Furthermore, the F191H/R changes neither affected the levels of interleukin-2 receptor expression and apoptosis of HIV-1-infected primary T cells nor reduced Nef-mediated induction of NFAT. Unexpectedly, the F191H change markedly reduced and the F191R mutation disrupted the ability of Nef to enhance virion infectivity in P4-CCR5 indicator cells but not in TZM-bl cells or peripheral blood mononuclear cells. Most importantly, all HIV-1 Nef mutants replicated efficiently and caused CD4
+
T-cell depletion in ex vivo-infected human lymphoid tissue. Altogether, our data show that the interaction of Nef with PAK2 does not play a major role in T-cell activation, viral replication, and apoptosis.
Epitope Mapping of the Hemagglutinin Molecule of a Highly Pathogenic H5N1 Influenza Virus by Using Monoclonal Antibodies
Authors: Kaverin Nikolai V. , Rudneva Irina A. , Govorkova Elena A. , Timofeeva Tatyana A. , Shilov Aleksandr A. , Kochergin-Nikitsky Konstantin S. , Krylov Piotr S. , Webster Robert G. 
Published: September 2007

ABSTRACT
We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) ΔHA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants’ HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.
Identification of a New Human Adenovirus Protein Encoded by a Novel Late
l
-Strand Transcription Unit
Authors: Tollefson Ann E. , Ying Baoling , Doronin Konstantin , Sidor Peter D. , Wold William S. M. 
Published: September 2007

ABSTRACT

A short open reading frame named the “U exon,” located on the adenovirus (Ad)
l
-strand (for leftward transcription) between the early E3 region and the
fiber
gene, is conserved in mastadenoviruses. We have observed that Ad5 mutants with large deletions in E3 that infringe on the U exon display a mild growth defect, as well as an aberrant Ad E2 DNA-binding protein (DBP) intranuclear localization pattern and an apparent failure to organize replication centers during late infection. Mutants in which the U exon DNA is reconstructed have a reversed phenotype. Chow et al. (L. T. Chow et al., J. Mol. Biol. 134:265-303, 1979) described mRNAs initiating in the region of the U exon and spliced to downstream sequences in the late DBP mRNA leader and the DBP-coding region. We have cloned this mRNA (as cDNA) from Ad5 late mRNA; the predicted protein is 217 amino acids, initiating in the U exon and continuing in frame in the DBP leader and in the DBP-coding region but in a different reading frame from DBP. Polyclonal and monoclonal antibodies generated against the predicted U exon protein (UXP) showed that UXP is ∼24K in size by immunoblot and is a late protein. At 18 to 24 h postinfection, UXP is strongly associated with nucleoli and is found throughout the nucleus; later, UXP is associated with the periphery of replication centers, suggesting a function relevant to Ad DNA replication or RNA transcription. UXP is expressed by all four species C Ads. When expressed in transient transfections, UXP complements the aberrant DBP localization pattern of UXP-negative Ad5 mutants. Our data indicate that UXP is a previously unrecognized protein derived from a novel late
l
-strand transcription unit.
Identification and Functional Analysis of Salmon Annexin 1 Induced by a Virus Infection in a Fish Cell Line
Authors: Hwang Hyun Jin , Moon Chang Hoon , Kim Han Geun , Kim Joo Yun , Lee Jung Min , Park Jeong Woo , Chung Dae Kyun 
Published: September 2007

ABSTRACTIn this study, we investigated changes in protein expression of fish cells induced by infection of infectious pancreatic necrosis virus (IPNV) using two-dimensional electrophoresis and matrix-assisted laser desorption-time of flight proton motive force analysis and identified a novel type of salmon annexin 1 that is induced in fish cells by infection with IPNV. Northern blotting showed that this annexin is overexpressed in IPNV-infected cells compared to control cells, and further analysis revealed that it has a 1,509-bp full-length cDNA sequence with an open reading frame encoding 339 amino acids (GenBank accession no. AY944135). Amino acid sequence analysis revealed that this protein belongs to the annexin 1 subfamily. By applying RNA interference, the mRNA levels of salmon annexin 1 were suppressed and, under these conditions, apoptosis of IPNV-infected cells was significantly increased. While small interfering RNA (siRNA) treatment did not affect the levels of the viral proteins significantly until 10 h postinfection, it reduced the titer of extracellular virus to 25% of that of a scrambled siRNA-treated control. These data provide evidence of an antiapoptotic function for salmon annexin 1 that is important for IPNV growth in cultured cells.
Occupational risks for adenocarcinoma of the nasal cavity and paranasal sinuses in the German wood industry
Authors: Pesch B , Pierl C B , Gebel M , Gross I , Becker D , Johnen G , Rihs H-P , Donhuijsen K , Lepentsiotis V , Meier M , Schulze J , Brüning T 
Published: September 2007

Objectives:To examine the risk of wood dust and chemical exposures for adenocarcinoma of the nasal cavity and paranasal sinuses (ADCN) among German wood workers.Methods:An industry-based case-control study with 86 male ADCN cases and 204 controls was conducted in the German wood-working industries. Cumulative and average wood-dust exposure was quantified with a job-exposure matrix based on wood-dust measurements at recent and historical workplaces. Probabilities of exposure to wood preservatives, stains, varnishes, and formaldehyde were semi-quantitatively rated. Odds ratios and 95% confidence intervals were calculated with logistic regression analysis conditional on age and adjusted for smoking and other factors. For estimating the risks of either wood dust or chemical additives, the authors additionally adjusted for the corresponding co-exposure.Results:ADCN occurred relatively more frequently among wood workers that had ever worked as cabinet makers or joiners (OR 2.96, 95% CI 1.46 to 6.01) than as saw millers (OR 0.15, 95% CI 0.03 to 0.68). Average exposure to inhalable wood dust ⩾5 mg/m3was associated with a high risk (OR 48.47, 95% CI 13.30 to 176.63) compared to levels below 3.5 mg/m3. Assuming 40 years of exposure under these concentrations, the corresponding OR was 4.20 (95% CI 1.69 to 10.43). Exposure between 3.5 and 5 mg/m3was also found to pose a risk (OR 10.54, 95% CI 3.34 to 33.27). Exposure to pigment stains before 1970 was associated with an increased risk (OR 3.03; 95% CI 1.11 to 8.26). No significant associations were estimated for wood preservatives, varnishes, and formaldehyde.Conclusions:The authors found an elevated ADCN risk for exposure to inhalable wood dust above 3.5 mg/m3. The rareness of the disease does not allow the exclusion of risk below that concentration. For pigment stains, there is evidence for an association of historical exposure with the development of ADCN in German wood workers.
Ultraviolet Laser Photoablation of Polymers: A Review and Recent Results
Authors: Lazare Sylvain , Granier Vincent 
Published: September 2007

The evolution since 1982, of far‐UV laser photoablation of polymers is described. The experimental data
can be fitted by using a dynamic model which states that the irradiated interface moves at a rate
proportional to the difference between, the intensity reaching it, and the ablation threshold intensity

urn:x-wiley:02786273:media:lc018750:lc018750-math-0001

.
The screening effect of the ablated gaseous products is taken into account. The experimental etch depth
versus fluence, obtained with our new quartz crystal microbalance technique, can be fitted by adjusting
two parameters of this model; the mean absorption coefficient of the products

urn:x-wiley:02786273:media:lc018750:lc018750-math-0002

and the so‐called ablation
rate constant k, which is the etch rate for

urn:x-wiley:02786273:media:lc018750:lc018750-math-0003

MW/cm2. These two parameters are wavelength
dependent. The model allows also the calculation of the dose of absorbed energy as a function of depth in
the material. For each layer of the ablated depth, the dose absorbed before and after (reabsorption of the
gas products) ablation are distinguished. The dose of reexcitation varies highly with fluence and the
distribution of gas products broadens accordingly. However, primary products need to be studied. Surface
products are formbd on the final surface, during the postablation phase of the pulsed irradiation. The
probable mechanism of the evolution of excitation energy is discussed, with stress on the elementary steps
leading to heat production.The perspectives of evolution of etching and patterning polymer surfaces by far‐UV photoablation are
high in basic research and technology.
Laser Induced Fluorescence of Resulting From the Thermal Energy Dissociative Charge Transfer Reaction
Authors: Lemaire j. , Marx R. , Savary F. Morlet 
Published: September 2007

The vibrational (and rotational) energy distribution of ions
produced in the He+/N2O charge transfer reaction at thermal
energy has been measured by laser induced fluorescence using
an Ion Cyclotron Resonance cell to store the ions. Vibrational
levels up to V" = 5 have been observed.The relaxation processes experienced by the (X) ions before
laser detection are discussed.
Polymeric Matrices for Lasing Dyes: Recent Developments
Authors: Costela A. , Garcia-Moreno I. , Figuera J. M. , Amat-Guerri F. , Sastre R. 
Published: September 2007

An overview of recent results obtained by our group on the development of polymeric
solid‐state media incorporating either Rhodamine or Coumarin dyes is presented. The
effect on the laser performance of the rigidity and viscoelastic properties of the polymeric
matrix has been investigated. Lasing efficiencies similar to those found in ethanolic
solution, and improved photochemical stability, as compared with that obtained in
previous polymeric materials, were demonstrated for solid solutions of Rhodamine 6G
(Rh6G) in appropriate copolymer formulations of 2‐hydroxyethyl methacrylate
(HEMA) and methyl methacrylate (MMA). Further improvements in photostability
were obtained when modified Rh6G molecules were copolymerized with HEMA and
MMA. When samples of this new highly homogeneous gain medium were placed in a
rotating system, where the laser medium was scanned in a continuous way, a stable laser
output with no sign of degradation after 500,000 shots was accomplished for transversal
pumping at 337 nm with 1.7 mJ pulses from a N2‐laser at 2 Hz repetition rate.The effect on laser operation of different polymerization methods, dye concentration,
and composition of the polymeric matrix was also investigated for Coumarin‐doped gain
media. Conditions were found that significantly improved both lasing efficiency and
photostability in Coumarin 540A (C540A)‐doped polymeric matrices. Insight into the
main photodegradation mechanisms of this dye was provided by the study of
fluorescence and lasing properties of a number of C540A solutions with increased
viscosity, from liquid solution to solid polymer matrix.
Transient Resonance RamanStudies of Ru(II) Complexes in DNAand in Homogeneous Media
Authors: Coates Colin G. , McGarvey John J. , Bell Steven E. J. , Jacquet Luc , Kelly John M. , Keyes Tia , Vos Johannes G. 
Published: September 2007

Transient resonance Raman (TR2) spectroscopy has been used to investigate the metalligand
charge‐transfer (MLCT) excited states of Ru(II) polypyridyl complexes inDNAand
in homogeneous solution. In DNA, complexes of the type [Ru(L)2(L′)]2+ were studied,
where L=2, 2’‐bipyridyl (bpy), 1,4, 5, 8‐tetraazaphenanthrene (tap), and L′ dipyrido
[3,2:a‐2′ ,3′:c]‐phenazine (dppz) or 1,4,5,8,9,12‐hexaazatriphenylene (HAT). For
[Ru(bpy)2(HAT)]2+, the enhancement pattern of vibrational modes in the TR2 spectra
attributable to reduced HAT⋅− in the triplet MLCT state suggest perturbations to the
intraligand transition of HAT⋅− in the presence of DNA. Transient RR spectra for
[Ru(tap)2(dppz)]2+ are indicative of formation of the species RunII(tap⋅−)(tap)(dppz) by
electron transfer from DNA to the triplet MLCT state of the complex.TR2 spectra for complexes of the type,
, n=1, 2 where L=a triazole
bridging ligand, illustrate the use of the technique as a probe of the response of MLCT
states to the electronic environment.
Elman Backpropagation as Reinforcement for Simple Recurrent Networks
Authors: Grüning André 
Published: September 2007

Simple recurrent networks (SRNs) in symbolic time-series prediction (e.g., language processing models) are frequently trained with gradient descent--based learning algorithms, notably with variants of backpropagation (BP). A major drawback for the cognitive plausibility of BP is that it is a supervised scheme in which a teacher has to provide a fully specified target answer. Yet agents in natural environments often receive summary feedback about the degree of success or failure only, a view adopted in reinforcement learning schemes. In this work, we show that for SRNs in prediction tasks for which there is a probability interpretation of the network's output vector, Elman BP can be reimplemented as a reinforcement learning scheme for which the expected weight updates agree with the ones from traditional Elman BP. Network simulations on formal languages corroborate this result and show that the learning behaviors of Elman backpropagation and its reinforcement variant are very similar also in online learning tasks.
Three-Dimensional Mesoscale Dipole Frontal Collisions
Authors: Dubosq Sara , Viúdez Álvaro 
Published: September 2007

Abstract
Frontal collisions of mesoscale baroclinic dipoles are numerically investigated using a three-dimensional, Boussinesq, and f-plane numerical model that explicitly conserves potential vorticity on isopycnals. The initial conditions, obtained using the potential vorticity initialization approach, consist of twin baroclinic dipoles, balanced (void of waves) and static and inertially stable, moving in opposite directions. The dipoles may collide in a close-to-axial way (cyclone–anticyclone collisions) or nonaxially (cyclone–cyclone or anticyclone–anticyclone collisions). The results show that the interacting vortices may bounce back and interchange partners, may merge reaching a tripole state, or may squeeze between the outer vortices. The formation of a stable tripole from two colliding dipoles is possible but is dependent on diffusion effects. It is found that the nonaxial dipole collisions can be characterized by the interchange between the domain-averaged potential and kinetic energy. Dipole collisions in two-dimensional flow display also a variety of vortex interactions, qualitatively similar to the three-dimensional cases.