bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Presidential Puzzle: Political Cycles and the Stock Market
Authors: Santa‐Clara Pedro , Valkanov Rossen 
Published: September 2003

AbstractThe excess return in the stock market is higher under Democratic than Republican presidencies: 9 percent for the value‐weighted and 16 percent for the equal‐weighted portfolio. The difference comes from higher real stock returns and lower real interest rates, is statistically significant, and is robust in subsamples. The difference in returns is not explained by business‐cycle variables related to expected returns, and is not concentrated around election dates. There is no difference in the riskiness of the stock market across presidencies that could justify a risk premium. The difference in returns through the political cycle is therefore a puzzle.
Empirical Tests for Stochastic Dominance Efficiency
Authors: Post Thierry 
Published: September 2003

AbstractWe derive empirical tests for the stochastic dominance efficiency of a given portfolio with respect to all possible portfolios constructed from a set of assets. The tests can be computed using straightforward linear programming. Bootstrapping techniques and asymptotic distribution theory can approximate the sampling properties of the test results and allow for statistical inference. Our results could provide a stimulus to the further proliferation of stochastic dominance for the problem of portfolio selection and evaluation. Using our tests, the Fama and French market portfolio is significantly inefficient relative to benchmark portfolios formed on market capitalization and book‐to‐market equity ratio.
Do Spin‐offs Expropriate Wealth from Bondholders?
Authors: Maxwell William F. , Rao Ramesh P. 
Published: September 2003

AbstractA wealth transfer from bondholders to stockholders is one of several hypotheses used to explain stockholder gains on the announcement of a spin‐off. However, previous empirical research has not found systematic evidence supporting the wealth expropriation hypothesis. Using a larger sample with comprehensive bond data, we find evidence consistent with wealth expropriation. Bondholders, on average, suffer a significant negative abnormal return during the month of the spin‐off announcement. However, even accounting for the loss to the bondholders, the aggregate value of the publicly traded debt and equity increases on a spin‐off announcement, suggesting that the wealth expropriation hypothesis is not a complete explanation of the stockholder gains. In explaining the magnitude of the losses to bondholders, we find they are a function of the loss in collateral in the spun‐off subsidiary and the level of financial risk of the parent firm. Consistent with a loss to bondholders, firms are more likely to have their credit rating downgraded than upgraded after a spin‐off. Additionally, consistent with the wealth transfer hypothesis, losses to bondholders tend to be more severe, the larger the gains to shareholders.
Family Firms
Authors: Burkart Mike , Panunzi Fausto , Shleifer Andrei 
Published: September 2003

AbstractWe present a model of succession in a firm owned and managed by its founder. The founder decides between hiring a professional manager or leaving management to his heir, as well as on what fraction of the company to float on the stock exchange. We assume that a professional is a better manager than the heir, and describe how the founder's decision is shaped by the legal environment. This theory of separation of ownership from management includes the Anglo‐Saxon and the Continental European patterns of corporate governance as special cases, and generates additional empirical predictions consistent with cross‐country evidence.
Organization of Human Papillomavirus Productive Cycle during Neoplastic Progression Provides a Basis for Selection of Diagnostic Markers
Authors: Middleton Kate , Peh Woei , Southern Shirley , Griffin Heather , Sotlar Karl , Nakahara Tomomi , El-Sherif Amira , Morris Lesley , Seth Rashmi , Hibma Merilyn , Jenkins David , Lambert Paul , Coleman Nicholas , Doorbar John 
Published: September 2003

ABSTRACT
The productive cycle of human papillomaviruses (HPVs) can be divided into discrete phases. Cell proliferation and episomal maintenance in the lower epithelial layers are followed by genome amplification and the expression of capsid proteins. These events, which occur in all productive infections, can be distinguished by using antibodies to viral gene products or to surrogate markers of their expression. Here we have compared precancerous lesions caused by HPV type 16 (HPV16) with lesions caused by HPV types that are not generally associated with human cancer. These include HPV2 and HPV11, which are related to HPV16 (supergroup A), as well as HPV1 and HPV65, which are evolutionarily divergent (supergroups E and B). HPV16-induced low-grade squamous intraepithelial lesions (CIN1) are productive infections which resemble those caused by other HPV types. During progression to cancer, however, the activation of late events is delayed, and the thickness of the proliferative compartment is progressively increased. In many HPV16-induced high-grade squamous intraepithelial lesions (CIN3), late events are restricted to small areas close to the epithelial surface. Such heterogeneity in the organization of the productive cycle was seen only in lesions caused by HPV16 and was not apparent when lesions caused by other HPV types were compared. By contrast, the order in which events in the productive cycle were initiated was invariant and did not depend on the infecting HPV type or the severity of disease. The distribution of viral gene products in the infected cervix depends on the extent to which the virus can complete its productive cycle, which in turn reflects the severity of cervical neoplasia. It appears from our work that the presence of such proteins in cells at the epithelial surface allows the severity of the underlying disease to be predicted and that markers of viral gene expression may improve cervical screening.
N-Linked Glycans with Similar Location in the Fusion Protein Head Modulate Paramyxovirus Fusion
Authors: von Messling Veronika , Cattaneo Roberto 
Published: September 2003

ABSTRACT

N-linked glycans not only orchestrate the folding and intracellular transport of viral glycoproteins but also modulate their function. We have characterized the three glycans attached to fusion (F) proteins of the morbilliviruses canine distemper virus and measles virus. The individual
Morbillivirus
glycans have similar functional properties: the glycan at position 68 is essential for protein transport, and those at positions 36 and 75 modulate fusion (numbering according to the Newcastle disease virus [NDV] F protein sequence). Based on the crystal structure of the NDV F protein, we then predicted the locations of the
Morbillivirus
glycans: the glycan at position 36 is located in the F protein head, and those at positions 68 and 75 are located near the neck-stalk interface. NDV position 36 is not occupied by a glycan; the only glycan in that F protein head also has a fusion control function and grows from residue 366, located only 6 Å from residue 36. We then exchanged the glycan at position 36 with the glycan at position 366 and showed functional complementation. Thus, structural information about the F proteins of
Paramyxoviridae
coupled with functional analysis disclosed a location in the protein head into which fusion-modulating glycans independently evolved.
Yeast-Derived Human Immunodeficiency Virus Type 1 p55gagVirus-Like Particles Activate Dendritic Cells (DCs) and Induce Perforin Expression in Gag-Specific CD8+T Cells by Cross-Presentation of DCs
Authors: Tsunetsugu-Yokota Yasuko , Morikawa Yuko , Isogai Maya , Kawana-Tachikawa Ai , Odawara Takashi , Nakamura Tetsuya , Grassi Fernanda , Autran Brigitte , Iwamoto Aikichi 
Published: September 2003

ABSTRACTTo evaluate the immunogenicity of human immunodeficiency virus (HIV) type 1 p55gagvirus-like particles (VLPs) released by budding from yeast spheroplasts, we have analyzed the effects of yeast VLPs on monocyte-derived dendritic cells (DCs). Yeast VLPs were efficiently incorporated into DCs via both macropinocytosis and endocytosis mediated by mannose-recognizing receptors, but not the mannose receptor. The uptake of yeast VLPs induced DC maturation and enhanced cytokine production, notably, interleukin-12 p70. We showed that yeast membrane components may contribute to DC maturation partly through Toll-like receptor 2 signaling. Thus, Gag particles encapsulated by yeast membrane may have an advantage in stimulating Gag-specific immune responses. We found that yeast VLPs, but not the control yeast membrane fraction, were able to activate both CD4+and CD8+T cells of HIV-infected individuals. We tested the effect of cross-presentation of VLP by DCs in two subjects recruited into a long-term nonprogressor-slow progressor cohort. When yeast VLP-loaded DCs of these patients were cocultured with peripheral blood mononuclear cells for 7 days, approximately one-third of the Gag-specific CD8+T cells were activated and became perforin positive. However, some of the Gag-specific CD8+T cells appeared to be lost during in vitro culture, especially in a patient with a high virus load. Our results suggest that DCs loaded with yeast VLPs can activate Gag-specific memory CD8+T cells to become effector cells in chronically HIV-infected individuals, but there still remain unresponsive Gag-specific T-cell populations in these patients.
Characterization of RNA Elements That Regulate Gag-Pol Ribosomal Frameshifting in Equine Infectious Anemia Virus
Authors: Chen Chaoping , Montelaro Ronald C. 
Published: September 2003

ABSTRACT

Synthesis of Gag-Pol polyproteins of retroviruses requires ribosomes to shift translational reading frame once or twice in a −1 direction to read through the stop codon in the
gag
reading frame. It is generally believed that a slippery sequence and a downstream RNA structure are required for the programmed −1 ribosomal frameshifting. However, the mechanism regulating the Gag-Pol frameshifting remains poorly understood. In this report, we have defined specific mRNA elements required for sufficient ribosomal frameshifting in equine anemia infectious virus (EIAV) by using full-length provirus replication and Gag/Gag-Pol expression systems. The results of these studies revealed that frameshifting efficiency and viral replication were dependent on a characteristic slippery sequence, a five-base-paired GC stretch, and a pseudoknot structure. Heterologous slippery sequences from human immunodeficiency virus type 1 and visna virus were able to substitute for the EIAV slippery sequence in supporting EIAV replication. Disruption of the GC-paired stretch abolished the frameshifting required for viral replication, and disruption of the pseudoknot reduced the frameshifting efficiency by 60%. Our data indicated that maintenance of the essential RNA signals (slippery sequences and structural elements) in this region of the genomic mRNA was critical for sufficient ribosomal frameshifting and EIAV replication, while concomitant alterations in the amino acids translated from the same region of the mRNA could be tolerated during replication. The data further indicated that proviral mutations that reduced frameshifting efficiency by as much as 50% continued to sustain viral replication and that greater reductions in frameshifting efficiency lead to replication defects. These studies define for the first time the RNA sequence and structural determinants of Gag-Pol frameshifting necessary for EIAV replication, reveal novel aspects relative to frameshifting elements described for other retroviruses, and provide new genetic determinants that can be evaluated as potential antiviral targets.
New Inhibitors of Scrapie-Associated Prion Protein Formation in a Library of 2,000 Drugs and Natural Products
Authors: Kocisko David A. , Baron Gerald S. , Rubenstein Richard , Chen Jiancao , Kuizon Salomon , Caughey Byron 
Published: September 2003

ABSTRACT

Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (PrP) in the brain. One approach to TSE therapeutics is the inhibition of PrP accumulation. Indeed, many inhibitors of the accumulation of PrP associated with scrapie (PrP
Sc
) in scrapie-infected mouse neuroblastoma cells (ScN
2
a) also have antiscrapie activity in rodents. To expedite the search for potential TSE therapeutic agents, we have developed a high-throughput screening assay for PrP
Sc
inhibitors using ScN
2
a cells in a 96-well format. A library of 2,000 drugs and natural products was screened in ScN
2
a cells infected with scrapie strain RML (Chandler) or 22L. Forty compounds were found to have concentrations causing 50% inhibition (IC
50
s) of PrP
Sc
accumulation of ≤10 μM against both strains. Seventeen had IC
50
s of ≤1 μM against both strains. Several classes of compounds were represented in the 17 most potent inhibitors, including naturally occurring polyphenols (e.g., tannic acid and tea extracts), phenothiazines, antihistamines, statins, and antimalarial compounds. These 17 compounds were also evaluated in a solid-phase cell-free hamster PrP conversion assay. Only the polyphenols inhibited the cell-free reaction, and their IC
50
s were near 100 nM. Several of the new PrP
Sc
inhibitors cross the blood-brain barrier and thus have potential to be effective after TSE infection reaches the brain. The fact that many are either approved human drugs or edible natural products should facilitate their use in animal testing and clinical trials.
Early Transcription from Nonintegrated DNA in Human Immunodeficiency Virus Infection
Authors: Wu Yuntao , Marsh Jon W. 
Published: September 2003

ABSTRACT

Replication of human immunodeficiency virus (HIV) involves obligatory sequential processes. Following viral entry and reverse transcription, the newly synthesized viral DNA integrates into the host chromatin. Integration is mandatory for viral production, yet HIV infection of CD4 T cells in vivo results in high levels of nonintegrated DNA. The biological potential of nonintegrated HIV DNA is unclear; however, prior work has demonstrated a limited transcription of the
nef
gene by nonintegrated HIV in infected quiescent T-cell populations. In a kinetic analysis of HIV infection of metabolically active transformed and primary CD4 T cells, we find an unexpected transient expression of both early and late message by nonintegrated HIV DNA. However, only the early multiply spliced transcript was measurably translated. This restriction of protein expression was due in part to inadequate Rev function, since expression of Rev in
trans
resulted in the expression of the late structural gene
gag
by nonintegrated HIV DNA.
Tacaribe Virus Z Protein Interacts with the L Polymerase Protein To Inhibit Viral RNA Synthesis
Authors: Jácamo Rodrigo , López Nora , Wilda Maximiliano , Franze-Fernández María T. 
Published: September 2003

ABSTRACT

Tacaribe virus (TV) is the prototype of the New World group of arenaviruses. The TV genome encodes four proteins, the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a small RING finger protein (Z). Using a reverse genetic system, we recently demonstrated that TV N and L are sufficient to drive transcription and full-cycle RNA replication mediated by TV-like RNAs and that Z is a powerful inhibitor of these processes (N. López, R. Jácamo, and M. T. Franze-Fernández, J. Virol. 65:12241-12251, 2001). In the present study we investigated whether Z might interact with either of the proteins, N and L, required for RNA synthesis. To that end, we used coimmunoprecipitation with monospecific antibodies against the viral proteins and coimmunoprecipitation with serum against glutathione
S
-transferase (GST) and binding to glutathione-Sepharose beads when Z was expressed as a fusion protein with GST. We demonstrated that Z interacted with L but not with N and that Z inhibitory activity was dependent on its ability to bind to L. We also evaluated the contribution of different Z regions to its binding ability and functional activity. We found that integrity of the RING structure is essential for Z binding to L and for Z inhibitory activity. Mutants with deletions at the N and C termini of Z showed that amino acids within the C-terminal region and immediately adjacent to the RING domain N terminus contribute to efficient Z-L interaction and are required for inhibitory activity. The data presented here provide the first evidence of an interaction between Z and L, suggesting that Z interferes with viral RNA synthesis by direct interaction with L. In addition, coimmunoprecipitation studies revealed a previously unreported interaction between N and L.
An Alphavirus Replicon Particle Chimera Derived from Venezuelan Equine Encephalitis and Sindbis Viruses Is a Potent Gene-Based Vaccine Delivery Vector
Authors: Perri Silvia , Greer Catherine E. , Thudium Kent , Doe Barbara , Legg Harold , Liu Hong , Romero Raul E. , Tang Zequn , Bin Qian , Dubensky Thomas W. , Vajdy Michael , Otten Gillis R. , Polo John M. 
Published: September 2003

ABSTRACTAlphavirus replicon particle-based vaccine vectors derived from Sindbis virus (SIN), Semliki Forest virus, and Venezuelan equine encephalitis virus (VEE) have been shown to induce robust antigen-specific cellular, humoral, and mucosal immune responses in many animal models of infectious disease and cancer. However, since little is known about the relative potencies among these different vectors, we compared the immunogenicity of replicon particle vectors derived from two very different parental alphaviruses, VEE and SIN, expressing a human immunodeficiency virus type 1 p55Gagantigen. Moreover, to explore the potential benefits of combining elements from different alphaviruses, we generated replicon particle chimeras of SIN and VEE. Two distinct strategies were used to produce particles with VEE-p55gagreplicon RNA packaged within SIN envelope glycoproteins and SIN-p55gagreplicon RNA within VEE envelope glycoproteins. Each replicon particle configuration induced Gag-specific CD8+T-cell responses in murine models when administered alone or after priming with DNA. However, Gag-specific responses varied dramatically, with the strongest responses to this particular antigen correlating with the VEE replicon RNA, irrespective of the source of envelope glycoproteins. Comparing the replicons with respect to heterologous gene expression levels and sensitivity to alpha/beta interferon in cultured cells indicated that each might contribute to potency differences. This work shows that combining desirable elements from VEE and SIN into a replicon particle chimera may be a valuable approach toward the goal of developing vaccine vectors with optimal in vivo potency, ease of production, and safety.
Human Immunodeficiency Virus Type 1 Induces Persistent Changes in Mucosal and Blood γδ T Cells despite Suppressive Therapy
Authors: Poles Michael A. , Barsoum Shady , Yu Wenjie , Yu Jian , Sun Patricia , Daly Jeanine , He Tian , Mehandru Saurabh , Talal Andrew , Markowitz Martin , Hurley Arlene , Ho David , Zhang Linqi 
Published: September 2003

ABSTRACTγδ T cells are primarily found in the gastrointestinal mucosa and play an important role in the first line of defense against viral, bacterial, and fungal pathogens. We sought to examine the impact of human immunodeficiency virus type 1 (HIV-1) infection on mucosal as well as peripheral blood γδ T-cell populations. Our results demonstrate that HIV-1 infection is associated with significant expansion of Vδ1 and contraction of Vδ2 cell populations in both the mucosa and peripheral blood. Such changes were observed during acute HIV-1 infection and persisted throughout the chronic phase, without apparent reversion after treatment with highly active antiretroviral therapy (HAART). Despite an increase in the expression of CCR9 and CD103 mucosal homing receptors on peripheral blood γδ T cells in infected individuals, mucosal and peripheral blood γδ T cells appeared to be distinct populations, as reflected by distinct CDR3 length polymorphisms and sequences in the two compartments. Although the underlying mechanism responsible for triggering the expansion of Vδ1 γδ T cells remains unknown, HIV-1 infection appears to have a dramatic impact on γδ T cells, which could have important implications for HIV-1 pathogenesis.
Identification of the Receptor Binding Domain of the Mouse Mammary Tumor Virus Envelope Protein
Authors: Zhang Yuanming , Rassa John C. , deObaldia Maria Elena , Albritton Lorraine M. , Ross Susan R. 
Published: September 2003

ABSTRACT

Mouse mammary tumor virus
(MMTV) is a betaretrovirus that infects rodent cells and uses mouse transferrin receptor 1 for cell entry. To characterize the interaction of MMTV with its receptor, we aligned the MMTV envelope surface (SU) protein with that of Friend murine leukemia virus (F-MLV) and identified a putative receptor-binding domain (RBD) that included a receptor binding sequence (RBS) of five amino acids and a heparin-binding domain (HBD). Mutation of the HBD reduced virus infectivity, and soluble heparan sulfate blocked infection of cells by wild-type pseudovirus. Interestingly, some but not all MMTV-like elements found in primary and cultured human breast cancer cell lines, termed h-MTVs, had sequence alterations in the putative RBS. Single substitution of one of the amino acids found in an h-MTV RBS variant in the RBD of MMTV, Phe
40
to Ser, did not alter species tropism but abolished both virus binding to cells and infectivity. Neutralizing anti-SU monoclonal antibodies also recognized a glutathione
S
-transferase fusion protein that contained the five-amino-acid RBS region from MMTV. The critical Phe
40
residue is located on a surface of the MMTV RBD model that is distant from and may be structurally more rigid than the region of F-MLV RBD that contains its critical binding site residues. This suggests that, in contrast to other murine retroviruses, binding to its receptor may result in few or no changes in MMTV envelope protein conformation.
Influenza B Virus BM2 Protein Is Transported through the
trans-
Golgi Network as an Integral Membrane Protein
Authors: Watanabe Shinji , Imai Masaki , Ohara Yoshiro , Odagiri Takato 
Published: September 2003

ABSTRACT

A bicistronic mRNA transcribed from the influenza B virus RNA segment 7 encodes two viral proteins, matrix protein M1 and uncharacterized small protein BM2. In the present study, we focused on the cytoplasmic transport and cellular membrane association of BM2. Immunofluorescence studies of virus-infected cells indicated that BM2 accumulated at the Golgi apparatus immediately after synthesis and then was transported to the plasma membrane through the
trans
-Golgi network. Localization of a set of BM2 deletion mutants revealed that the N-terminal half of BM2 (residues 2 to 50) was crucial for its transport; in particular, the deletion of residues 2 to 23, deduced to be a transmembrane domain, resulted in diffused distribution of the protein throughout the entire cell. Sucrose gradient flotation and biochemical analyses of the membrane showed that BM2 was tightly associated with cellular membranes as an integral membrane protein. Oligomerization of BM2 was demonstrated by coprecipitation of differentially epitope-tagged BM2 proteins. Taken together, these results strongly suggest that BM2 is integrated into the plasma membrane at the N-terminal hydrophobic domain as fourth membrane protein, in addition to hemagglutinin, neuraminidase, and NB, of the influenza B virus.