bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrametropolitan Location and Office Market Dynamics
Authors: Clapp John , Pollakowski Henry O. , Lynford Lloyd 
Published: September 2003

Theory and evidence point to interdependency between office location decisions and dynamic growth paths. For example, clerical and administrative support employees are suburbanizing relatively rapidly in most markets in response to changes in technology and transportation. This paper tests the hypothesis that both cross‐sectional and dynamic variables are important determinants of dynamic patterns and office market forecasts.County Business Patterns data at the county and town levels indicate substantial spatial specialization (i.e., agglomeration) by type of office activity. But these agglomerations do shift over time, as indicated by the maintained hypothesis. Our econometric estimates suggest that the demand for office space in submarkets is responsive to agglomerations by type of industry as well as to growth in FIRE employment. The supply of office space is responsive to lagged expected demand.
Potential Beneficiaries from Reverse Mortgage Products for Elderly Homeowners: An Analysis of American Housing Survey Data
Authors: Merrill Sally R. , Finkel Meryl , Kutty Nandinee K. 
Published: September 2003

A variety of reverse mortgage loan programs have been available to elderly households for over a decade. The number of unrestricted reverse mortgage loans issued by the private sector has been quite small. About 12,000 loans have been issued through mid‐1992. Some researchers take this to mean that the size of the potential market for reverse mortgages is also quite small. Other researchers claim that current low levels of activity reflect supply and demand problems, but that the potential market is in fact quite large.This paper uses American Housing Survey (AHS) data to estimate the potential size of the market for unrestricted reverse mortgages. The 1989 national AHS shows that there are over twelve million elderly homeowners (age 62 and over) who own their homes free and clear. Depending on their income, age and the level of home equity, the group of households most likely to benefit from reverse annuity mortgages is considerably smaller. As one approach to defining a lower bound of the estimate of potential beneficiaries from reverse mortgages, we count the number of homeowners in a prime group consisting of the older elderly, aged 70 or above, with an annual income of $30,000 or less, with home equity between $100,000 and $200,000, who have lived in their homes for over ten years. We estimate that there are about 800,000 elderly households in this prime group. For such households, reverse mortgage payments could represent a substantial percentage increase in income; other definitions of target groups can also be explored using the tables provided.The paper uses the 1985 through 1988 AHS Standard Metropolitan Statistical Area (SMSA) surveys to identify areas that have a large number of elderly homeowners in the prime target group, and in which these homeowners represent a large fraction of the elderly homeowner population. These locations are likely targets for introduction of reverse mortgage products because any campaign can be targeted towards a high concentration of likely eligible beneficiaries.
Pathogenicity of Different Baboon
Herpesvirus Papio 2
Isolates Is Characterized by either Extreme Neurovirulence or Complete Apathogenicity
Authors: Rogers Kristin M. , Ealey Katie A. , Ritchey Jerry W. , Black Darla H. , Eberle R. 
Published: September 2003

ABSTRACT

In comparisons of the pathogenicity of simian alphaherpesviruses in mice, two isolates of the baboon virus HVP2 were nearly as lethal as monkey B virus, a biological safety level 4 agent (J. W. Ritchey, K. A. Ealey, M. Payton, and R. Eberle, J. Comp. Pathol.
127:
150-161, 2002). To confirm these results, mice were inoculated intramuscularly with 10
5
PFU of HVP2 isolates obtained from different baboon subspecies and primate centers. Some of the HVP2 isolates (6 of 13) caused paralysis and death in the mice, while 7 of 13 HVP2 isolates produced no clinical signs of disease. The apathogenic HVP2 isolates (HVP2
ap
) induced only low levels of serum antiviral immunoglobulin G relative to levels observed in sera from mice infected with the neurovirulent isolates of HVP2 (HVP2
nv
). Histological examination of tissues from mice inoculated with HVP2
nv
isolates showed extensive neural tissue destruction, while mice infected with HVP2
ap
isolates showed no lesions. Tissue samples collected at 48-h intervals postinfection suggested that HVP2
ap
isolates failed to replicate at the site of inoculation. There was no significant difference in the in vitro replication, plaque size, or cytopathic effect morphology of HVP2
ap
versus HVP2
nv
isolates. While HVP2 isolates replicated better in Vero monkey kidney cells than in murine L cells, plaquing efficiency of individual isolates did not correlate with the dichotomous pathogenic properties seen in mice. Phylogenetic analyses of both coding and intergenic regions (US4-6) of the HVP2 genome separated isolates into two distinct clades that correlated with the two in vivo virulence phenotypes. Taken together, these results demonstrate that two subtypes of HVP2 exist that are very closely related but differ dramatically in their ability to cause disease in a murine model.
AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine
Authors: Pistello Mauro , Matteucci Donatella , Bonci Francesca , Isola Patrizia , Mazzetti Paola , Zaccaro Lucia , Merico Antonio , Del Mauro Daniela , Flynn Norman , Bendinelli Mauro 
Published: September 2003

ABSTRACT
Feline immunodeficiency virus (FIV) infection of domestic cats represents a valuable system through which to investigate criteria for antilentiviral vaccines in a natural host species. Here, we examined whether vaccination with a strain of FIV attenuated as a result of prolonged growth in vitro could protect against a fully virulent, highly heterologous intraclade challenge. The results indicated that the vaccine virus produced a low-grade infection with no detectable pathological effects and afforded a long-lasting sterilizing immunity if the challenge was delivered intraperitoneally as cell-free virus but not against a cell-associated intravaginal challenge. In the latter case, however, the replication and pathological consequences of the challenge virus were markedly suppressed. Together with similar results obtained in rhesus monkey models, these findings should give impulse to the development of attenuated FIV vaccines to be tested in controlled studies in field cats. Field studies may provide answers to some of the existing safety concerns surrounding attenuated AIDS vaccines in humans.
Persistence and Dissemination of Simian Retrovirus Type 2 DNA in Relation to Viremia, Seroresponse, and Experimental Transmissibility in
Macaca fascicularis
Authors: Wilkinson Roseanne C. , Murrell Claire K. , Guy Rebecca , Davis Gail , Hall Joanna M. , North David C. , Rose Nicola J. , Almond Neil 
Published: September 2003

ABSTRACT

Endemic simian retrovirus (SRV) infection can cause fatal simian AIDS in
Macaca fascicularis
, but many individuals survive with few clinical signs. To further clarify the parameters of SRV pathogenesis, we investigated the persistence of viral DNA forms in relation to active viremia, antibody response, and transmissibility of infection. In
M. fascicularis
from endemically SRV-2-infected colonies, viral DNA was present in both linear and unintegrated long terminal repeat circular forms in peripheral blood mononuclear cells of all viremic and many nonviremic animals. Long-term followup of three individuals with distinct infection patterns demonstrated persistence of linear and circular forms of viral DNA in peripheral blood mononuclear cells and tissues, irrespective of viremia or antibody status, but reactivation of latent infections was not observed. The role of viral DNA in transmission and early pathogenesis of SRV-2 was investigated by inoculation of SRV-2 DNA-positive blood into groups of naïve
M. fascicularis
from either a viremic or nonviremic donor and subsequent analysis of the virological and serological status of the recipients. Transmission of SRV and development of anti-SRV antibodies were only observed in recipients of blood from the viremic donor; transfer of SRV provirus and unintegrated circular DNA in blood from the nonviremic donor did not lead to infection of the recipients. These results indicate that a proportion of
M. fascicularis
are able to effectively control the replication and infectivity of SRV despite long-term persistence of viral DNA forms in infected lymphocytes.
Tyrosine Residues Direct the Ubiquitination and Degradation of the NY-1 Hantavirus G1 Cytoplasmic Tail
Authors: Geimonen Erika , Fernandez Imelyn , Gavrilovskaya Irina N. , Mackow Erich R. 
Published: September 2003

ABSTRACTThe hantavirus G1 protein contains a long C-terminal cytoplasmic tail of 142 residues. Hantavirus pulmonary syndrome-associated hantaviruses contain conserved tyrosine residues near the C terminus of G1 which form an immunoreceptor tyrosine activation motif (ITAM) and interact with Src and Syk family kinases. During studies of the G1 ITAM we observed that fusion proteins containing the G1 cytoplasmic tail were poorly expressed. Expression of G1 cytoplasmic tail constructs were dramatically enhanced by treating cells with the proteasome inhibitor ALLN, suggesting that the protein is ubiquitinated and degraded via the 26S proteasome. By using a 6-His-tagged ubiquitin, we demonstrated that the G1 cytoplasmic tail is polyubiquitinated and degraded in the absence of proteasome inhibitors. Expression of only the ITAM-containing domain also directed protein ubiquitination and degradation in the absence of upstream residues. Deleting the C-terminal 51 residues of G1, including the ITAM, stabilized G1 and blocked polyubiquitination and degradation of the protein. Site-directed mutagenesis of both ITAM tyrosines (Y619 and Y632) to phenylalanine also blocked polyubiquitination of G1 proteins and dramatically enhanced G1 protein stability. In contrast, the presence of Y627, which is not part of the ITAM motif, had no effect on G1 stability. Mutagenesis of just Y619 enhanced G1 stability, inhibited G1 ubiquitination, and increased the half-life of G1 by threefold. Mutating only Y632 had less of an effect on G1 protein stability, although Y619 and Y632 synergistically contributed to G1 instability. These findings suggest that Y619, which is conserved in all hantaviruses, is the primary signal for directing G1 ubiquitination and degradation. Collectively these findings indicate that specific conserved tyrosines within the G1 cytoplasmic tail direct the polyubiquitination and degradation of expressed G1 proteins and provide a potential means for down-regulating hantavirus G1 surface glycoproteins and cellular proteins that interact with G1.
Cytopathic and Noncytopathic Interferon Responses in Cells Expressing Hepatitis C Virus Subgenomic Replicons
Authors: Guo Ju-Tao , Zhu Qing , Seeger Christoph 
Published: September 2003

ABSTRACTHepatitis C virus (HCV) is the only known positive-stranded RNA virus that causes persistent lifelong infections in humans. Accumulation of HCV RNA can be inhibited with alpha interferon (IFN-α) in vivo and in culture cells. We used cell-based assay systems to investigate the mechanisms responsible for the cytokine-induced inhibition of HCV replication. The results showed that IFN-α could suppress the accumulation of viral RNA by a noncytopathic pathway and could also induce apoptosis of virally infected cells in a concentration- and cell line-dependent fashion. Whereas the noncytopathic IFN-α response depended on a functional Jak-STAT signal transduction pathway, it did not appear to require double-stranded RNA-dependent pathways. Moreover, we found that functional proteasomes were required for establishment of the IFN-α response against HCV. Based on the results described in this study we propose a model for the mechanism by which IFN-α therapy suppresses HCV replication in chronic infections by both cytopathic and noncytopathic means.
Oral Vaccination of Mice with Adenoviral Vectors Is Not Impaired by Preexisting Immunity to the Vaccine Carrier
Authors: Xiang Z. Q. , Gao G. P. , Reyes-Sandoval A. , Li Y. , Wilson J. M. , Ertl H. C. J. 
Published: September 2003

ABSTRACTE1 deletion adenoviral vectors of the human serotype 5 (AdHu5) and the chimpanzee serotype 68 (AdC68) expressing the rabies virus glycoprotein (rab.gp) were tested for induction of transgene product-specific antibodies upon intranasal or oral immunization of newborn mice. Both vectors induced antibodies to rabies virus that could be detected in serum and mucosal secretions. Serum rabies virus-neutralizing antibody titers sufficed to protect neonatally vaccinated mice against a subsequent challenge with rabies virus. The efficacy of the AdHu5rab.gp vector given orally to newborn mice born to AdHu5-immune dams was not impaired by maternally transferred antibodies to the vaccine carrier.
Coordinate Replication of Alfalfa Mosaic Virus RNAs 1 and 2 Involves
cis
- and
trans
-Acting Functions of the Encoded Helicase-Like and Polymerase-Like Domains
Authors: Vlot A. Corina , Laros Sebastiaan M. , Bol John F. 
Published: September 2003

ABSTRACT

RNAs 1 and 2 of the tripartite genome of alfalfa mosaic virus encode the replicase proteins P1 and P2, respectively, whereas RNA 3 encodes the movement protein and coat protein. Transient expression of wild-type (wt) and mutant viral RNAs and proteins by agroinfiltration of plant leaves was used to study
cis
- and
trans
-acting functions of the helicase-like domain in P1 and the polymerase-like domain in P2. Three mutations in conserved motifs of the helicase-like domain of P1 affected one or more steps leading to synthesis of minus-strand RNAs 1, 2, and 3. In leaves containing transiently expressed P1 and P2, replication of wt but not mutant RNA 1 was observed. Apparently, the transiently expressed P1 could not complement the defect in replication of the RNA 1 mutant. Moreover, the transiently expressed wt replicase supported replication of RNA 2, but this replication was blocked in
trans
by coexpression of mutant RNA 1. However, expression of mutant RNA 1 did not interfere with the replication of RNA 3 by the wt replicase. Similarly, a mutation in the GDD motif encoded by RNA 2 could not be complemented in
trans
and affected the replication of RNA 1 by a wt replicase, while replication of RNA 3 remained unaffected. In competition assays, the transient wt replicase preferentially replicated RNA 3 over RNAs 1 and 2. The results indicate that one or more functions of P1 and P2 act in
cis
and point to the existence of a mechanism that coordinates the replication of RNAs 1 and 2.
Aichi Virus Leader Protein Is Involved in Viral RNA Replication and Encapsidation
Authors: Sasaki Jun , Nagashima Shigeo , Taniguchi Koki 
Published: September 2003

ABSTRACT

Aichi virus
, a member of the family
Picornaviridae
, encodes a leader (L) protein of 170 amino acids (aa). The Aichi virus L protein exhibits no significant sequence homology to those of other picornaviruses. In this study, we investigated the function of the Aichi virus L protein in virus growth. In vitro translation and cleavage assays indicated that the L protein has no autocatalytic activity and is not involved in polyprotein cleavage. The L-VP0 junction was cleaved by 3C proteinase. Immunoblot analysis showed that the L protein is stably present in infected cells. Characterization of various L mutants derived from an infectious cDNA clone revealed that deletion of 93 aa of the center part (aa 43 to 135), 50 aa of the N-terminal part (aa 4 to 53), or 90 aa of the C-terminal part (aa 74 to 163) abolished viral RNA replication. A mutant (Δ114-163) in which 50 aa of the C-terminal part (aa 114 to 163) were deleted exhibited efficient RNA replication and translation abilities, but the virus yield was 4 log orders lower than that of the wild type. Sedimentation analysis of viral particles generated in mutant Δ114-163 RNA-transfected cells showed that the mutant has a severe defect in the formation of mature virions, but not in that of empty capsids. Thus, the data obtained in this study indicate that the Aichi virus L protein is involved in both viral RNA replication and encapsidation.
Mapping of Abutilon Mosaic Geminivirus Minichromosomes
Authors: Pilartz Marcel , Jeske Holger 
Published: September 2003

ABSTRACTThe single-stranded circular DNA ofAbutilon mosaic geminivirionsis complemented to double-stranded DNA by host proteins after infecting cells. This double-stranded DNA serves as a template for replication as well as transcription and is assembled into host nucleosomes, yielding circular viral minichromosomes. Their chromatin structure was analyzed by use of isolated nuclei combining nuclease sensitivity assays with ligation-mediated PCR, evaluating nucleosomal ladders and topoisomer distributions in one- and two-dimensional gels by blot hybridization. Viral minichromosomes were found to exist in at least two defined structures covered with 11 or 12 nucleosomes, leaving open gaps accessible for interactions with other host factors. Nucleosome-free gaps were colocalized with promoter structures and the origin of replication in both components of genomic DNA (DNA A and DNA B). Nucleosomes were positioned over the entire viral DNA in at least two alternative phases with different periodicities. The distribution of topoisomers of monomeric viral circular double-stranded DNA confirmed the presence of variable chromatin structures revealing maximum frequencies of molecules with either 11, 12, or 13 superhelical turns (corresponding to respective numbers of nucleosomes) at maximal frequency at different stages during leaf development of infected plants. The role of variable chromatin structures for gene regulation of geminiviruses is discussed.
Effects of Human Metapneumovirus and Respiratory Syncytial Virus Antigen Insertion in Two 3′ Proximal Genome Positions of Bovine/Human Parainfluenza Virus Type 3 on Virus Replication and Immunogenicity
Authors: Tang Roderick S. , Schickli Jeanne H. , MacPhail Mia , Fernandes Fiona , Bicha Leenas , Spaete Joshua , Fouchier Ron A. M. , Osterhaus Albert D. M. E. , Spaete Richard , Haller Aurelia A. 
Published: September 2003

ABSTRACT
A live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory syncytial virus (RSV). RSV and hMPV are both paramyxoviruses that cause respiratory disease in young children, the elderly, and immunocompromised individuals. RSV has been known for decades to cause acute lower respiratory tract infections in young children, which often result in hospitalization, while hMPV has only been recently identified as a novel human respiratory pathogen. In this study, the ability of bovine/human PIV3 to express three different foreign transmembrane surface glycoproteins and to induce a protective immune response was evaluated. The RNA-dependent RNA polymerase of paramyxoviruses binds to a single site at the 3′ end of the viral RNA genome to initiate transcription of viral genes. The genome position of the viral gene determines its level of gene expression. The promoter-proximal gene is transcribed with the highest frequency, and each downstream gene is transcribed less often due to attenuation of transcription at each gene junction. This feature of paramyxoviruses was exploited using the PIV3 vector by inserting the foreign viral genes at the 3′ terminus, at position 1 or 2, of the viral RNA genome. These locations were expected to yield high levels of foreign viral protein expression stimulating a protective immune response. The immunogenicity and protection results obtained with a hamster model showed that bovine/human PIV3 can be employed to generate bivalent PIV3/RSV or PIV3/hMPV vaccine candidates that will be further evaluated for safety and efficacy in primates.
Early Control of Highly Pathogenic Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimeric Virus Infections in Rhesus Monkeys Usually Results in Long-Lasting Asymptomatic Clinical Outcomes
Authors: Igarashi Tatsuhiko , Endo Yasuyuki , Nishimura Yoshiaki , Buckler Charles , Sadjadpour Reza , Donau Olivia K. , Dumaurier Marie-Jeanne , Plishka Ronald J. , Buckler-White Alicia , Martin Malcolm A. 
Published: September 2003

ABSTRACTIn contrast to simian immunodeficiency viruses (SIVs), which induce immunodeficiency over a 1- to 2-year period, highly pathogenic simian-human immunodeficiency viruses (SHIVs) cause an irreversible and systemic depletion of CD4+T lymphocytes in macaque monkeys within weeks of inoculation. Nonetheless, the seemingly more aggressive SHIVs have proven to be easier to control by the same vaccine regimens which fail to contain SIV. Because early events during in vivo infections may determine both the pathogenic consequences of the challenge virus and its sensitivity to interventions that prevent disease, we have evaluated the effects of inoculum size and a potent antiretroviral drug on the development of disease in monkeys infected with SHIVDH12R. The results obtained show that in a majority of inoculated animals, suppression of SHIV replication during the first 2 weeks of infection, which prevents complete loss of CD4+T cells, leads to very low to undetectable postpeak viremia and an asymptomatic clinical course for periods up to 4 years.
Role of the Mutation Q252R in Activating Membrane Fusion in the Murine Leukemia Virus Surface Envelope Protein
Authors: Lu Chi-Wei , Roth Monica J. 
Published: September 2003

ABSTRACT
Entry of retroviruses into host cells requires the fusion between the viral and cellular membranes. It is unclear how receptor binding induces conformational changes within the surface envelope protein (SU) that activate the fusion machinery residing in the transmembrane envelope protein (TM). In this report, we have isolated a point mutation, Q252R, within the proline-rich region of the 4070A murine leukemia virus SU that altered the virus-cell binding characteristics and induced cell-cell fusion. Q252R displays a SU shedding-sensitive phenotype. Cell-cell fusion is receptor dependent and is observed only in the presence of MuLV Gag-Pol. Both cellular binding and fusion by Q252R are greatly enhanced in conjunction of G100R, a mutation within the SU variable region A which increases viral binding through an independent mechanism. Deletion of a conserved histidine (His36) at the SU N terminus abolished cell-cell fusion by G100R/Q252R Env without compromising virus-cell binding. Although G100R/Q252R virus has no detectable titer, replacement of the N-terminal nine 4070A SU amino acids with the equivalent ecotropic MuLV sequence restored viral infectivity. These studies provide insights into the functional cooperation between multiple elements of SU required to signal receptor binding and activate the fusion machinery.